Académique Documents
Professionnel Documents
Culture Documents
A R T I C L E I N F O A B S T R A C T
Keywords: Curcuma longa is a rhizomatous perennial herb that belongs to the family Zingiberaceae, native to South Asia and
Curcuma longa is commonly known as turmeric. It is used as herbal remedy due to the prevalent belief that the plant has medical
Curcumin properties. C. longa possesses different effects such as antioxidant, anti-tumor, antimicrobial, anti-inflammatory,
Natural toxins wound healing, and gastroprotective activities. The recent studies have shown that C. longa and curcumin, its
Chemical toxins
important active ingredient, have protective effects against toxic agents. In this review article, we collected in
Protective effects
vitro and animal studies which are related to protective effects of turmeric and its active ingredient against
Toxicology
natural and chemical toxic agents.
Nowadays, herbal medicines are used in different diseases. The re- 2. Methods
cent studies have shown some plants including black cumin [1], saffron
[2], barberry [3] and green tea [4] have antidotal or protective effects In this review article, we collected different research projects in
against toxic agents in different tissues. Curcuma longa (turmeric), na- scientific databases such as MEDLINE, Scopus, Web of Science data-
tive to tropical South Asia, belongs to the Zingiberaceae family. There bases and local references, which study the protective or antidotal ef-
are about 133 species of C. longa in worldwide. Turmeric is used in fects of C. longa and its major components against natural toxins and
food, cosmetic and pharmaceutical industries. More than 100 active chemical-induced toxicity. Studies were identified through electronic
compounds are found in this herb. The root is composed of volatile oil databases from their inception up to Jun 2017. The keywords for the
such as turmerone and coloring ingredient which is known to curcu- search were: Curcuma longa, turmeric, curcumin, natural toxin, anti-
minoids [5]. The d-α-phellandrene, cinol, d-sabinene borneol, sesqui- dote, chemical toxin and protective effects.
terpenes and zingiberene are identified as volatile oil [6]. Curcumin, as
curcuminoids, is an important compound in turmeric. It has different 3. Natural toxins
biological activities such as antioxidant [7], anti-carcinogenic [8,9] and
anti-inflammatory activity [10,11]. The most of pharmacological ef- According to recent studies, C. longa or curcumin has antidotal ef-
fects of turmeric are related to the presence of curcumin which has anti- fects against some natural toxins in different organs.
oxidant activity. In vivo and in vitro studies have shown that this herb
has different pharmacological effects. In folk medicine, turmeric is used 3.1. Aflatoxin
for respiratory diseases such as allergy, liver problems, sinusitis and
anorexia [12]. Nowadays other effects have identified from this med- 3.1.1. Nephroprotective
icinal herb such as anticancer [13,14], cardioprotective [15], hepato- Aflatoxins (AFs) as mycotoxin are produced by Aspergillus species.
protective [16,17], antiarthritic properties [18] and hypoglycemic The four major forms of aflatoxin including B1, B2, G1, and G2 which
[19]. Also it is applied in oral cancer, skin cancer [20], stomach cancer aflatoxin B1 has more toxicity than other aflatoxins [26]. The toxicity of
[21] and metabolic syndrome [22]. The studies have reported the aflatoxins is appeared as hemorrhage, growth retardation, heart and
protective effects of C. longa and its active components against toxic kidney, damage to liver, and death [27,28]. Aflatoxin increased urea,
agents in different tissues such as liver [23], brain [24] and Cr and uric acid while decreased total protein levels. It causes dilation
⁎
Corresponding author at: Pharmaceutical Research Center, Institute of Pharmaceutical Technology, Mashhad University of Medical Sciences, Mashhad, Iran.
E-mail address: Hosseinzadehh@mums.ac.ir (H. Hosseinzadeh).
https://doi.org/10.1016/j.biopha.2018.01.072
Received 26 September 2017; Received in revised form 11 January 2018; Accepted 11 January 2018
0753-3322/ © 2018 Elsevier Masson SAS. All rights reserved.
A. Hosseini, H. Hosseinzadeh Biomedicine & Pharmacotherapy 99 (2018) 411–421
Table 1
Nephroprotective effects of C. longa and curcumin against chemical or natural toxins.
Extract decreased Cr, BUN, uric acid and necrosis of kidney C. longa mice Acetaminophen [47]
The level of CYP2E1, iNOSgene IL-1β and TNF-α decreased. The Antioxidant enzymes Curcumin rats Acetaminophen [49]
increased
Reduced serum urea, creatinine and lipid peroxidation Curcumin and curcumin rats Cisplatin [56]
nanoparticles
Curcumin increased the levels of NAMPT and SIRT proteins, decreased serum urea, MDA Curcumin rats Cisplatin [57]
and kidney injury
Decreased MDA, serum urea and creatinine while increment of GSH, SOD and total protein C. onga rats Acrylamid [61]
Reduced urea, cr, uric acid, pro-apoptotic and pro-inflammatory gens. Increased Curcumin rats Aflatoxin [29]
antioxidant content
Reduced BUN, urea, Cr and MDA Curcumin rats Sodium fluoride [66]
Decreased urea, Cr, lipid peroxidation. Increased the expression of Nrf2/HO-1 and Sirt1 Curcumin rats Gentamicin [71–73]
Decreased MDA, elevated GSH,SOD and CAT Curcumin rats Cadmium [77]
Creatinin (Cr), Blood Urea Nitrogen (BUN), Catalase (CAT), Malondialdehyde (MDA), Super Oxide Dismutase (SOD), Glutathion (GSH), nuclear factor erythroid 2–related factor 2 (Nrf2),
and sirtuin (Sirt).
of capillaries, enlargement of glomeruli and necrosis. It increased pro- toxicity is related to ROS production and the formation of PGE2 and NO
apoptotic proteins such as bax and caspase3. Curcumin at dose of [37]. Also LPS leads to cardiac hypertrophy via increasing of histone
200 mg/kg was administrated for 4 weeks orally. It decreased aflatoxin acetylation in myocardium. Histones play a role in response to stress
toxicity in kidney via reduction of serum urea, creatinine, uric acid, stimulation in cardiac toxicity [38]. Also p300-HAT is responsible for
MDA and increasing of GSH, total protein levels. Curcumin also de- LPS-induced cardiac hypertrophy. Curcumin (100 μg/kg) reduced LPS
creased histopathological changes, pro-apoptotic proteins and pro-in- toxicity in cardiac tissues via remodeling of chromatin, especially his-
flammatory gen such as COX2 [29] (Table 1). tone acetylation and inhibition of p300 p300-HAT activity [39].
Table 2
Hepatoprotective effects of C. longa and curcumin against chemical or natural toxins.
CCl4 rats C.longa Elevated the level of nuclear translocated Nrf2, reduced AST, ALT and MDA [79,80]
Aflatoxin B1 rats Curcumin nanoparticle Decreased AST, ALT and MDA [34]
Thioacetamide rats C. longa Decreased MDA, nitrotyrosine, urinary 8-OH-dG, TGF-β and TNF-α. Increased [83]
antioxidant enzymes
Lead acetate rats C. longa Decreased liver enzymes and increased antioxidant content [90]
Lead acetate mice Curcumin or nanocurcumin Decreased liver enzymes and increased antioxidant content [91]
Cadmium rats C. longa Reduced HSC activity, liver fibrosis and hepatic enzymes [94]
Cadmium rats Curcumin Increased antioxidants, scavenge of ROS [95]
Mercury rats Curcumin Changed metallothionein mRNA, increased antioxidant content and chelated mercury [178]
Arsenic rats Curcumin Scavenging free radicals, chelating arsenicals compounds, reduction of lipid peroxidation [102]
Propanil rats Curcumin Reduction of ROS, lipid peroxidation and hepatic enzymes [104]
Cisplatin rats Curcumin Improved hepatic enzymes, liver histopathology, NADPH expression [106]
Nicotine mice Curcumin Reduction of oxidative stress and inflammatory cytokines such as TNF-a and IL-1, [111]
increased liver weight
Chromium rats Curcumin Improved hepatic structural, enzymes and antioxidant content [119]
Copper rats Curcumin Reduced lipid peroxidation, restored the GSH and antioxidant enzyme levels [122]
Diazinon rats Combination of curcumin and vitamin Elevation of catalase, glutathione peroxidase and glutathione-S-transferase [129]
E
Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Reactive Oxygen Species (ROS).
412
A. Hosseini, H. Hosseinzadeh Biomedicine & Pharmacotherapy 99 (2018) 411–421
increasing of GSH and decreasing of ROS, MDA and NO2 levels [42]. herbal medicines which involve in decreasing of acrylamide neuro-
toxicity. Mehri et al. showed thymoquinone [59] and linalool [60] have
3.2.3.2. D-galactosamine. D-Galactose induces aging processes in animal neuroprotective effects against acrylamide. C. longa (0.5%) was added
models via damage to hippocampal neurons, mitochondrial to standard diet. It decreased MDA, serum urea and creatinine levels,
dysfunction, and decreasing in protein content [43]. Curcumin at while it increased GSH, SOD and total protein levels in rats that re-
doses of 50 and 100 mg/kg decreased galactosamine-induced ceived acrylamide [61] (Table 1).
neurotoxicity via reduction of lipidperoxidation, protein oxidation,
inhibition of caspase3 expression and increasing of antioxidant 4.1.4. Sodium fluoride
content in hippocampus [44] (Fig. 2). Fluoride is an industrial agent and utilized in dental preparations,
water sources and food preparations [62]. Fluoride enters to blood as
4. Chemical-induced toxicity ion via gastrointestinal and lung pathways. The consumption of fluoride
causes systemic problems such as renal injury [63]. Fluoride leads to
4.1. Nephroprotective changes in renal including inflammation, fibrosis, tubular destruction
and medullar hyperemia [64]. The production of free radicals play a
4.1.1. Acetaminophen role in fluoride toxicity [64,65]. Curcumin, at doses of 10 and 20 mg/
Acetaminophen is used as analgesic and antipyretic medicine. The kg, reduced fluoride-toxicity in kidney by normalization of blood urea
overdose of acetaminophen causes renal toxicity in about 1–2% of pa- nitrogen, creatinine, and urea levels. Also curcumin increased anti-
tients. The poisoning of acetaminophen in renal is related to dysfunc- oxidant enzymes and decreased lipid peroxidation [66] (Table 1).
tion of oxidase isoenzymes which are found in the kidney. Also other
mechanisms play roles in toxicity such as prostaglandin synthetase and 4.1.5. Gentamicin
N-deacetylase enzymes. Glutathione has an important role in the neu- Gentamicin as an antibiotic is used for treatment of bacterial in-
tralization of acetaminophen toxicity [45]. Acetaminophen causes in- fection which is caused by gram negative bacteria. Gentamicin induces
creasing of creatinine, urea and BUN levels as well as the elevation of nephrotoxicity in 30% of patients who received drug for more than 7
proinflammatory cytokines such as TNF-α and IL-1β in the kidney tis- days [67]. The signs of renal dysfunction are as increasing of BUN level
sues. It increased MDA and NO while decreased GSH level, SOD and and reducing of glomerular filtration rate [68]. The mechanism of ne-
GPx activities. The extract of C. longa (400, 800 and 1000 mg/kg) phrotoxicity is related to production of free radicals such as superoxide
showed nephroprotective effects against acetaminophen via decreasing anions, hydroxyl radicals, hydrogen peroxide and reactive nitrogen
creatinine, BUN and uric acid levels while acetaminophen elevated species in the kidney [69,70]. The structure of kidney is changed as
these indexes. Probably, the protective effect of extract is related to degeneration of epithelial lining, disruption of brush borders, disrupted
binding to acetaminophen metabolites and decreasing of their affinity Bowman's capsule and thickening of afferent arteriole. Also, urea,
to cellular GSH. Therefore, C. longa elevated the level of GSH and led to creatinine, and uric acid levels were elevated in serum. Administration
increase in the excretion of acetaminophen metabolites [46,47]. Cur- of curcumin (200 mg/kg), with rosemary (220 mg/kg), and propolis
cumin at dose of 100 mg/kg reduced nephrotoxicity following acet- (100 mg/kg), ameliorated structural changes and declined urea, crea-
aminophen treatment and improved oxidant/antioxidant imbalance. tinine and uric acid levels [71]. Another study showed curcumin
The protective effect of curcumin may be due to anti-inflammatory, (200 mg/kg) increased the level of catalase, GSH, SOD and GPX activ-
antioxidant properties and scavenging of ROS. Also curcumin decreased ities while decreased lipid peroxidation [72]. Curcumin (100 mg/kg)
NO production via reducing of iNOS expression. Down-regulation of increased Nrf2/HO-1 and Sirt1expression while decreased oxidative
iNOS led to decreasing of TNF-α and IL-1β formation [48]. This me- stress [73] (Table 1).
chanism is related to anti-oxidant activity of curcumin [49] (Table 1).
4.1.6. Cadmium
4.1.2. Cisplatin Cadmium (Cd) belongs to heavy metals. It induces toxicity in hu-
Cisplatin as chemotherapeutic drug is applied for treatment of dif- mans and animals. Chronic exposure to Cd causes nephrotoxicity [74]
ferent tumors. The important side effect is nephrotoxicity and led to and skeletal damage [75] via production of reactive oxygen species
morbidity and mortality among patients. The toxicity mechanism of which causes oxidative stress and lipid peroxidation [74]. In addition,
cisplatin is due to inflammation and oxidative stress [50]. Also the le- the level of antioxidant enzymes such as SOD, CAT and GSH reduced in
vels of tumor necrosis factor-alpha (TNF-α) [51], peroxynitrite anions Cd toxicity [76]. Moreover, structural modifications were observed in
[52], superoxide anions [53], hydrogen peroxide [54], and hydroxyl renal tissues. Curcumin, at dose of 250 mg/kg, declined histological and
radicals increased following cisplatin consumption [55]. Cisplatin re- biochemical changes. It decreased MDA level, elevated GSH level and
duces the proteins such as nicotinamide phosphoribosyltransferase improved proximal tubular changes [77] (Table 1).
(NAMPT) and sirtuin (SIRT), which interfere in resistance to stress. Also
cisplatin disturbs renal function and elevates urea and creatinine levels 4.2. Hepatoprotective activity
in serum. Curcumin and curcumin nanoparticles reduced cisplatin
toxicity at doses of 30 and 60 mg/kg. These compounds reduced serum 4.2.1. Carbon tetrachloride (CCl4)
urea, creatinine levels and lipid peroxidation. Curcumin has protective Carbon tetrachloride (CCl4) is a toxic agent for liver and uses in
effects against cisplatin via anti-oxidant function [56]. Also in another experimental models for induction of hepatotoxicity. A single dose of
study curcumin at dose of 100 mg/kg decreased kidney injury via de- CCl4 causes liver problems via generation of ROS [14]. CCl4 is meta-
creasing of MDA, serum urea and creatinine levels in rats following bolized and produced free radicals such as trichloromethyl (CCl3%) and/
cisplatin injection. Also curcumin increased the levels of NAMPT and or trichloromethyl peroxyl (CCl3OO%). These free radicals attack to
SIRT proteins in rats treated with cisplatin [57] (Table 1). cellular molecules and lead to apoptosis and necrosis [78]. Adminis-
tration of C. longa (50 or 100 mg/kg) in CCl4-treated rats decreased
4.1.3. Acrylamide serum AST, ALT and MDA levels. The activity of antioxidant enzymes,
Acrylamide is a polymer and uses in industry [58]. Also it is pro- such as catalase, superoxide dismutase, and glutathione peroxidase
duced when foods are cooked at high temperatures. It leads to toxicity increased. Also the extract elevated the level of nuclear translocated
in different organs such as kidney. Acrylamide is metabolized and Nrf2. Increasing of Nrf2 led to activation of the antioxidant and phase II
generated reactive oxygen species which leads to oxidative stress, lipid detoxifying enzymes such as glutathione S-transferase. Therefore, C.
peroxidation and DNA damages. Recent studies have reported that longa has protective effects against CCl4 via increasing of antioxidant
413
A. Hosseini, H. Hosseinzadeh Biomedicine & Pharmacotherapy 99 (2018) 411–421
enzymes and activation of nuclear translocated Nrf2 [79,80] (Table 2). via reduction of lipid peroxidation, hepatic enzymes and increasing of
antioxidant enzymes [104] (Table 2).
4.2.2. Thioacetamide
Thioacetamide is a hepatotoxic agent and causes liver disorders in 4.2.8. Cisplatin
experimental models [81]. Hepatic microsomal cytochrome P4502E Cisplatin is chemotherapeutic drug and causes different side effects
converts thioacetamide to TAA-S -oxide (TASO) and then to toxic such as hepatotoxicity. The cisplatin mechanism for liver injury is re-
thioacetamide S-dioxide (TASO2) which TASO2 leads to liver cirrhosis. lated to oxidative stress and generation of ROS which damage to cell
Thioacetamide elevates the level of liver enzymes such as ALP, ALT, membrane [105,106]. The balance between oxidant and antioxidant is
AST and bilirubin [82]. C. longa extract at doses of 250 and 500 mg/kg disturbed [107]. Cisplatin increased MDA while declined SOD and
reduced the liver enzymes, MDA, nitrotyrosine, and urinary 8-OH-dG catalase. It increased the level of hepatic enzymes such as ALT and AST.
levels. The extract increased antioxidant enzymes such as SOD and Also the expression of NADPH oxidase gene increased in the presence of
catalase and reduced inflammatory factors such as TGF-β and TNF-α. cisplatin. Curcumin at dose of 200 mg/kg improved the liver enzymes,
However, C. longa reduced the progression of liver cirrhosis via anti- lipid peroxidation biomarker, liver histopathology and gene expression
oxidant and anti-inflammatory activities [83] (Table 2). of liver NADPH oxidase [106] (Table 2).
414
A. Hosseini, H. Hosseinzadeh Biomedicine & Pharmacotherapy 99 (2018) 411–421
4.3. Cardioprotective activity the activities of antioxidant enzymes [133] (Fig. 1).
415
A. Hosseini, H. Hosseinzadeh Biomedicine & Pharmacotherapy 99 (2018) 411–421
antioxidant defense [136] (Fig. 1). role in neurotoxicity and tardive dyskinesia of haloperidol [144], thus
curcumin at dose of 50 mg/kg reduced the signs of tardive dyskinesia
4.3.6. Cadmium via anti-oxidant activity [145] (Fig. 2).
Cadmium as a heavy metal causes environmental pollution.
Different sources are responsible for air pollution by cadmium such as 4.4.3. Mono sodium glutamate (MSG)
burning of fossil, phosphate fertilizers, production of iron and steel, and Mono sodium glutamate as a flavor enhancer causes neuronal signs
other activities [137]. Humans are contaminated with cadmium via such as weakness, dizziness and headache. MSG changes lipid perox-
different routes including lung and gastrointestinal tract [137]. Oxi- idation and antioxidant activity of enzymes in cerebral brain and other
dative stress plays a role in cadmium-induced toxicity in different tissue related regions [146]. Also behavioral abnormalities are observed with
via damage to vascular and hypertension [137]. The protective effect of MSG [147]. Curcumin (150 mg/kg) declined acetyl choline esterase
curcumin against cadmium toxicity has been reported. Curcumin at (AchE) activity and inflammation in neurons, thus protected neurons
doses of 50 or 100 mg/kg normalized vascular dysfunction and blood against MSG. Also curcumin reduced glutamate level and gene ex-
pressure following cadmium toxicity. The protective mechanism of pression of receptors including NMDA2B and mGLUR5 in brain hip-
curcumin is related to generation of endothelial nitric oxide synthase pocampus [148] (Fig. 2).
(eNOS) protein, elevation of GSH redox ratio and reduction of super-
oxide (O2−) production in vascular smooth muscle. Antioxidant ac- 4.4.4. Aluminium
tivity and chelating properties play a role in protective effects of cur- Aluminum as a heavy metal is found in food products and water.
cumin against cadmium [138] (Fig. 1). Aluminium induces neurotoxicity and is accompanied with Alzheimer’s
disease (AD). Aluminium prompts oxidative stress and elevates the level
4.3.7. Diesel exhaust particles (DEP) of amyloid beta in in vivo. Chronic exposure to aluminium increases
Diesel exhaust particles lead to cardiopulmonary problems. Also, lipid peroxidation, nitrite levels, reduces glutathione levels, catalase,
exposure to this agent causes inflammation of lung and peripheral superoxide dismutase and glutathione-S-transferase activity. Also, it
thrombotic events. DEP lead to elevation of plasma C-reactive protein leads to elevation of acetylcholinesterase activity. Curcumin (30 mg/
(CRP), TNF-α, plasminogen activator inhibitor-1 (PAI-1) levels and kg) reduced aluminium toxicity via memory improvement, decreased
systolic blood pressure (SBP). Curcumin reduced cardiotoxicity via anti- acetylcholinesterase activity, oxidative damage and aluminium con-
inflammatory effects. Also it decreased the levels of CRP and TNFα as centration. Thus, curcumin showed a neuroprotective effect against
well as PAI-1 activity [139] (Fig. 1). aluminium toxicity [149,150] (Fig. 2).
416
A. Hosseini, H. Hosseinzadeh Biomedicine & Pharmacotherapy 99 (2018) 411–421
of curcumin may be related to anti-inflammatory, anti-nociceptive, dysfunction [172]. Chlorpyrifos leads to toxicity in lung via production
antioxidant and calcium inhibitory effects [158]. Curcumin decreased of free radicals, lipidperoxidation and reduction of antioxidant en-
lipid peroxidation, nitric oxide and TNF-α level while elevated anti- zymes. Curcumin at doses of 100 and 300 mg/kg in combination with
oxidant levels such as GSH, SOD, CAT and GPx (Fig. 2). vitamin E decreased these changes via scavenging of ROS and elevation
of antioxidant enzymes [173].
4.4.10. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
MPTP is converted to MPP + which is a neurotoxin agent in dopa- 4.5.2. Paraquat
minergic neurons and causes Parkinson via oxidative stress [159]. CNB- Paraquat damages to lung and leads to pulmonary fibrosis via
001 (24 mg/kg) is derived from curcumin and has therapeutic effects production of free radicals, releasing of inflammatory factors and pro-
against MPTP-induced Parkinson via decreasing of oxidative stress, teolytic enzymes. Paraquat at dose of 50 mg/kg increases alkaline
reduction of dopamine transporter and tyrosine hydroxylase expression phosphatase, angiotensin converting enzyme and N-acetyl-beta-D-glu-
[160] (Fig. 2). cosaminidase. Also it elevates MDA, neutrophils and decreases glu-
tathione. Curcumin reduced the toxicity via anti-inflammatory and
4.4.11. Pentylenetetrazole (PTZ) antioxidant activities [174].
PTZ is used for induction of seizure in experimental animals [161].
Curcumin at doses of 100 mg/kg and 300 mg/kg prevented PTZ effects 4.6. Genoprotective
via reducing oxidative stress, improvement of mitochondrial function
and memory in rats [162] (Fig. 2). 4.6.1. Chromium trioxide
Chromium belongs to heavy metals and is widely used by human in
4.4.12. Sevoflurane (SEVO) different industries. Also there is in air as Cr (III) and Cr (VI) which Cr
SEVO is used as inhalational anesthetic agent but it causes neuro- (VI) is more toxic because of it converts to Cr (III) that crosses cell
logical problem in the brain and damages to neurons. Curcumin re- membrane and binds to macromolecules. It damages to DNA via free
duced the side effects of sevoflurane via reducing of oxidative stress, radical production and causes genotoxicity. The studies have shown
inflammation, apoptosis and improvement of cognitive function [163] curcumin reduced chromium-induced genotoxicity [175].
(Fig. 2).
4.6.2. Cyclophosphamide
4.4.13. Acrylamide (ACR) Cyclophosphamide is used as anti-cancer drug. It damages to pro-
ACR is used in preparation of dyes, paper and plastic. Also it is tein structure via binding to DNA and RNA. Also it disturbs chromo-
produced in food when the temperature is high. ACR is absorbed from somal structure in different steps of spermatogenesis in germ cells.
skin easily and entered to organs [164]. It is especially toxic for neurons Curcumin at doses of 10, 15 and 20 mg/kg reduced the percentage of
and some studies have reported the protective effects of herbal medi- abnormal sperms following cyclophosphamide administration in mice.
cines such as crocin in in vivo [165] and in vitro against ACR [166]. Therefore, curcumin has protective effects against drugs which induce
Curcumin at dose of 50 mg/kg ameliorated ACR-induced neurotoxicity genotoxicity [176].
via reduction of oxidative stress. It elevated antioxidant content and
improved mitochondrial function. Also the activity of acet- 4.6.3. Copper
ylcholinesterase is restored to normal level in rats which received The studies have shown exposure to high concentration of copper
curcumin. However, curcumin decreased ACR-toxicity via reduction of leads to DNA damage and genotoxicity. The exposure with curcumin)
oxidative stress, amelioration of acetylcholinesterase activity and de- 0.2% (could decrease genotoxicity of copper in mice [177].
creasing function of cytosolic calcium [167] (Fig. 2).
5. Conclusion
4.4.14. Streptozotocin (STZ)
Streptozotocin is used for induction of Alzheimer's disease in animal Nowadays herbal medicines are used in most of diseases because of
models. The studies have shown that curcumin has a protective effect different properties such as antioxidant effects. Exposure to chemical
against STZ-induced neurotoxicity via reducing of oxidative stress and and natural toxins for long term can lead to toxicity in animal or
apoptosis. Also it decreased the storage of β-amyloid in the brain and human. These toxins cause toxicity in different organs including car-
led to improvement of cognitive problems [168] (Fig. 2). diovascular system, brain, liver, renal and lung. The recent studies have
shown herbal medicines play roles in reduction of toxicity of these
4.4.15. Arsenic agents. One of herbal medicine which has more pharmacological effects
Arsenic is belonging to heavy metals. It is toxic for different tissues is C. longa and its active constituent, curcumin. Most of studies have
such as brain [169]. Curcumin and nanoparticle of curcumin have shown that C. longa and its active compounds reduced nephrotoxicity,
protective effects against arsenic toxicity. They decreased lipid perox- hepatotoxicity, cardiotoxicity, neurotoxicity and lung toxicity mainly
idation and ROS production while increased antioxidant content in the through the reduction of inflammatory cytokines, antioxidant and an-
brain [170] (Fig. 2). tiapoptotic effects.
4.5. Lung protective [1] A. Tavakkoli, A. Ahmadi, B.M. Razavi, H. Hosseinzadeh, Black seed (Nigella sa-
tiva) and its constituent thymoquinone as an antidote or a protective agent against
natural or chemical toxicities, Iran. J. Pharm. Res. 16 (2017) 2–23.
4.5.1. Chlorpyrifos [2] B.M. Razavi, H. Hosseinzadeh, Saffron as an antidote or a protective agent against
Chlorpyrifos is used in agriculture industry. Chlorpyrifos causes natural or chemical toxicities, DARU J. Pharm. Sci. 23 (1) (2015) 31.
different side effects including genotoxicity, teratogenicity, hematolo- [3] N. Mohammadzadeh, S. Mehri, H. Hosseinzadeh, Berberis vulgaris and its con-
stituent berberine as antidotes and protective agents against natural or chemical
gical and immunological abnormalities, neurotoxicity, and hepatic
417
A. Hosseini, H. Hosseinzadeh Biomedicine & Pharmacotherapy 99 (2018) 411–421
toxicities, Iran. J. Basic Med. Sci. 20 (5) (2017) 538. biomarkers status, Toxicology 268 (1) (2010) 104–110.
[4] M. Rameshrad, B.M. Razavi, H. Hosseinzadeh, Protective effects of green tea and [33] V.S. Mary, M.G. Theumer, S.L. Arias, H.R. Rubinstein, Reactive oxygen species
its main constituents against natural and chemical toxins: a comprehensive re- sources and biomolecular oxidative damage induced by aflatoxin B1 and fumo-
view, Food Chem. Toxicol. 100 (2016) 115–137. nisin B1 in rat spleen mononuclear cells, Toxicology 302 (2) (2012) 299–307.
[5] A. Ruby, G. Kuttan, K.D. Babu, K. Rajasekharan, R. Kuttan, Anti-tumour and an- [34] M.A. Abdel-Wahhab, A.S. Salman, M.I. Ibrahim, A.A. El-Kady, S.H. Abdel-Aziem,
tioxidant activity of natural curcuminoids, Cancer Lett. 94 (1) (1995) 79–83. N.S. Hassan, A.I. Waly, Curcumin nanoparticles loaded hydrogels protects against
[6] M. Ohshiro, M. Kuroyanagi, A. Ueno, Structures of sesquiterpenes from Curcuma aflatoxin B 1-induced genotoxicity in rat liver, Food Chem. Toxicol. 94 (2016)
longa, Phytochem. 29 (7) (1990) 2201–2205. 159–171.
[7] T. Ak, İ. Gülçin, Antioxidant and radical scavenging properties of curcumin, Chem. [35] M. Rossol, H. Heine, U. Meusch, D. Quandt, C. Klein, M.J. Sweet, S. Hauschildt,
Biol. Interact. 174 (1) (2008) 27–37. LPS-induced cytokine production in human monocytes and macrophages, Crit.
[8] Y. Shukla, A. Arora, P. Taneja, Antimutagenic potential of curcumin on chromo- Rev. Immunol. (5) (2011) 31.
somal aberrations in Wistar rats, Mutat. Res. Genet. Toxicol. Environ. Mutagen [36] Y. Yoshinaga, T. Ukai, T. Kaneko, S. Nakatsu, C. Shiraishi, A. Kuramoto, K. Oshino,
515 (1) (2002) 197–202. I. Ichimura, Y. Hara, Topical application of lipopolysaccharide into gingival sulcus
[9] A. Sahebkar, Curcumin: A natural multitarget treatment for pancreatic cancer, promotes periodontal destruction in rats immunized with lipopolysaccharide, J.
Integr. Cancer Ther. 15 (3) (2016) 333–334. Periodontal. Res. 47 (5) (2012) 674–680.
[10] J.S. Jurenka, Anti-inflammatory properties of curcumin, a major constituent of [37] M.D. Díaz-Muñoz, I.C. Osma-García, M. Fresno, M.A. Iñiguez, Involvement of
Curcuma longa: a review of preclinical and clinical research, Altern. Med. Rev. 14 PGE2 and the cAMP signalling pathway in the up-regulation of COX-2 and mPGES-
(2) (2009). 1 expression in LPS-activated macrophages, Biochem. J. 443 (2) (2012) 451–461.
[11] Y. Panahi, M.S. Hosseini, N. Khalili, E. Naimi, M. Majeed, A. Sahebkar, [38] J. Backs, E.N. Olson, Control of cardiac growth by histone acetylation/deacety-
Antioxidant and anti-inflammatory effects of curcuminoid-piperine combination lation, Circ. Res. 98 (1) (2006) 15–24.
in subjects with metabolic syndrome: a randomized controlled trial and an up- [39] R. Chowdhury, R. Nimmanapalli, T. Graham, G. Reddy, Curcumin attenuation of
dated meta-analysis, Clin. Nutr. 34 (6) (2015) 1101–1108. lipopolysaccharide induced cardiac hypertrophy in rodents, ISRN Inflamm. 2013
[12] C. Araujo, L. Leon, Biological activities of Curcuma longa L, Mem. Inst. Oswaldo (2013).
Cruz 96 (5) (2001) 723–728. [40] R. Pirie, P. Dixon, B. McGorum, Endotoxin contamination contributes to the pul-
[13] R. Garg, A. Ingle, G. Maru, Dietary turmeric modulates DMBA-induced p21 ras, monary inflammatory and functional response to Aspergillus fumigatus extract
MAP kinases and AP-1/NF-κB pathway to alter cellular responses during hamster inhalation in heaves horses, Clin. Exp. Allergy 33 (9) (2003) 1183–1189.
buccal pouch carcinogenesis, Toxicol. Appl. Pharmacol. 232 (3) (2008) 428–439. [41] C. Sandersen, D. Bienzle, S. Cerri, T. Franck, S. Derochette, P. Neven, A. Mouytis-
[14] W. Zhu, P. Fung, The roles played by crucial free radicals like lipid free radicals, Mickalad, D. Serteyn, Effect of inhaled hydrosoluble curcumin on inflammatory
nitric oxide, and enzymes NOS and NADPH in CCl 4-induced acute liver injury of markers in broncho-alveolar lavage fluid of horses with LPS-induced lung neu-
mice, Free Radic. Biol. Med. 29 (9) (2000) 870–880. trophilia, Multidiscip. Respir. Med. 10 (1) (2015) 16.
[15] I. Mohanty, D.S. Arya, S.K. Gupta, Effect of Curcuma longa and Ocimum sanctum [42] P. Kumar, S. Padi, P. Naidu, A. Kumar, Possible neuroprotective mechanisms of
on myocardial apoptosis in experimentally induced myocardial ischemic-re- curcumin in attenuating 3-nitropropionic acid-induced neurotoxicity, Methods
perfusion injury, BMC Complement. Altern. Med. 6 (1) (2006) 3. Find. Exp. Clin. Pharmacol. 29 (1) (2007) 19–26.
[16] M. Miyakoshi, Y. Yamaguchi, R. Takagaki, K. Mizutani, T. Kambara, T. Ikeda, [43] J. Long, X. Wang, H. Gao, Z. Liu, C. Liu, M. Miao, X. Cui, L. Packer, J. Liu, D-
M. Zaman, H. Kakihara, A. Takenaka, K. Igarashi, Hepatoprotective effect of ses- galactose toxicity in mice is associated with mitochondrial dysfunction: protecting
quiterpenes in turmeric, Biofactors 21 (1–4) (2004) 167–170. effects of mitochondrial nutrient R-alpha-lipoic acid, Biogerontology 8 (3) (2007)
[17] S. Rahmani, S. Asgary, G. Askari, M. Keshvari, M. Hatamipour, A. Feizi, 373–381.
A. Sahebkar, Treatment of non‐alcoholic fatty liver disease with curcumin: a [44] O.J. Banji, D. Banji, K. Ch, Curcumin and hesperidin improve cognition by sup-
randomized placebo‐controlled trial, Phytother. Res. 30 (9) (2016) 1540–1548. pressing mitochondrial dysfunction and apoptosis induced by D-galactose in rat
[18] J.L. Funk, J.B. Frye, J.N. Oyarzo, N. Kuscuoglu, J. Wilson, G. McCaffrey, brain, Food Chem. Toxicol. 74 (2014) 51–59.
G. Stafford, G. Chen, R.C. Lantz, S.D. Jolad, Efficacy and mechanism of action of [45] J.G. Bessems, N.P. Vermeulen, Paracetamol (acetaminophen)-induced toxicity:
turmeric supplements in the treatment of experimental arthritis, Arthr. molecular and biochemical mechanisms, analogues and protective approaches,
Rheumatol. 54 (11) (2006) 3452–3464. Crit. Rev. Toxicol. 31 (1) (2001) 55–138.
[19] S. Honda, F. Aoki, H. Tanaka, H. Kishida, T. Nishiyama, S. Okada, I. Matsumoto, [46] M. Susan, M. Rao, Induction of glutathione S-transferase activity by curcumin in
K. Abe, T. Mae, Effects of ingested turmeric oleoresin on glucose and lipid meta- mice, Arzneimittelforschung 42 (7) (1992) 962–964.
bolisms in obese diabetic mice: a DNA microarray study, J. Agric. Food Chem. 54 [47] L. Khorsandi, M. Orazizadeh, Protective effect of curcuma longa extract on acet-
(24) (2006) 9055–9062. aminophen induced nephrotoxicity in mice, DARU 16 (3) (2008) 155–159.
[20] I.M. Villaseñor, M.K.B. Simon, A.M. Villanueva, Comparative potencies of nu- [48] J. Ghosh, J. Das, P. Manna, P.C. Sil, Acetaminophen induced renal injury via
traceuticals in chemically induced skin tumor prevention, Nutr. Cancer 44 (1) oxidative stress and TNF-α production: therapeutic potential of arjunolic acid,
(2002) 66–70. Toxicol. 268 (1) (2010) 8–18.
[21] M.A. Azuine, S.V. Bhide, Protective single/combined treatment with betel leaf and [49] A.F.M. Ismail, A.A. Salem, Renoprotective effect of curcumin on acetaminophen-
turmeric against methyl (acetoxymethyl) nitrosamine- induced hamster oral car- induced nephrotoxicity in rats, J. Chem. Pharm. Res. 8 (2) (2016) 773–779.
cinogenesis, Int. J. Cancer 51 (3) (1992) 412–415. [50] S.Y. Saad, M.M. Arafah, T.A. Najjar, Effects of mycophenolate mofetil on cisplatin-
[22] A. Mohammadi, H.R. Sadeghnia, M. Saberi-Karimian, H. Safarian, G.A. Ferns, induced renal dysfunction in rats, Cancer Chemother. Pharmacol. 59 (4) (2007)
M. Ghayour-Mobarhan, A. Sahebkar, Effects of curcumin on serum vitamin E 455–460.
concentrations in individuals with metabolic syndrome, Phytother. Res. 31 (4) [51] G. Ramesh, W.B. Reeves, TNF-α mediates chemokine and cytokine expression and
(2017) 657–662. renal injury in cisplatin nephrotoxicity, J. Clin. Invest. 110 (6) (2002) 835.
[23] T. Farkhondeh, S. Samarghandian, The hepatoprotective effects of curcumin [52] R. Srivastava, A. Farookh, N. Ahmad, M. Misra, S. Hasan, M. Husain, Evidence for
against drugs and toxic agents: an updated review, Toxin Rev. 35 (3–4) (2016) the involvement of nitric oxide in cisplatin-induced toxicity in rats, Biometals 9 (2)
133–140. (1996) 139–142.
[24] T. Farkhondeh, S. Samarghandian, F. Samini, Antidotal effects of curcumin against [53] C.A. Davis, H.S. Nick, A. Agarwal, Manganese superoxide dismutase attenuates
neurotoxic agents: an updated review, Asian Pac. J. Trop. Med. 9 (10) (2016) cisplatin-induced renal injury: importance of superoxide, J. Am. Soc. Nephrol. 12
947–953. (12) (2001) 2683–2690.
[25] T. Farkhondeh, S. Samarghandian, Antidotal effects of curcumin against agents- [54] S.M. Baek, C.H. Kwon, J.H. Kim, J.S. Woo, J.S. Jung, Y.K. Kim, Differential roles of
induced cardiovascular toxicity, Cardiovasc. Haematol. Disord. Drug Targets hydrogen peroxide and hydroxyl radical in cisplatin-induced cell death in renal
(Formerly Curr. Drug Targets Cardiovasc. Hematol. Disord.) 16 (1) (2016) 30–37. proximal tubular epithelial cells, J. Lab. Clin. Med. 142 (3) (2003) 178–186.
[26] A. Al-Ghasham, H.S. Ata, S. El-Deep, A.-R. Meki, S. Shehada, Study of protective [55] İ. Durak, H. Özbek, M. Karaayvaz, H.S. Öztürk, Cisplatin induces acute renal
effect of date and Nigella sativa on aflatoxin B1 toxicity, Inter. J. Health Sci. 2 (2) failure by impairing antioxidant system in guinea pigs: effects of antioxidant
(2008) 26. supplementation on the cisplatin nephrotoxicity, Drug Chem. Toxicol. 25 (1)
[27] C.P. Wild, Y.Y. Gong, Mycotoxins and human disease: a largely ignored global (2002) 1–8.
health issue, Carcinogen 31 (1) (2009) 71–82. [56] S.A. El-Rahman, S. Al-Jameel, Protection of curcumin and curcumin nanoparticles
[28] H. Abu-EL-Zahab, A. Abdel Aziz, D. Yossri, Studies on detoxification of aflatoxins against cisplatin induced nephrotoxicity in male rats, Scholars Acad. J. Biosci. 2
contaminated rabbits’ rations treated with clay and ammonia, Life Sci. J. 9 (3) (3) (2014) 214–223.
(2012). [57] S. Ugur, R. Ulu, A. Dogukan, A. Gurel, I.P. Yigit, N. Gozel, B. Aygen, N. Ilhan, The
[29] A.M. El-Mahalaway, Protective effect of curcumin against experimentally induced renoprotective effect of curcumin in cisplatin-induced nephrotoxicity, Ren. Fail.
aflatoxicosis on the renal cortex of adult male albino rats: a histological and im- 37 (2) (2015) 332–336.
munohisochemical study, Int. J. Clin. Exp. Pathol. 8 (6) (2015) 6019. [58] M. Nordin-Andersson, E. Walum, P. Kjellstrand, A. Forsby, Acrylamide-induced
[30] V.S. Mary, A. Valdehita, J.M. Navas, H.R. Rubinstein, M.L. Fernández-Cruz, Effects effects on general and neurospecific cellular functions during exposure and re-
of aflatoxin B 1, fumonisin B 1 and their mixture on the aryl hydrocarbon receptor covery, Cell Biol. Toxicol. 19 (1) (2003) 43–51.
and cytochrome P450 1A induction, Food Chem. Toxicol. 75 (2015) 104–111. [59] S. Mehri, M. Shahi, B.M. Razavi, F.V. Hassani, H. Hosseinzadeh, Neuroprotective
[31] G. Sun, S. Wang, X. Hu, J. Su, Y. Zhang, Y. Xie, H. Zhang, L. Tang, J.-S. Wang, Co- effect of thymoquinone in acrylamide-induced neurotoxicity in Wistar rats, Iran. J.
contamination of aflatoxin B1 and fumonisin B1 in food and human dietary ex- Basic Med. Sci. 17 (12) (2014) 1007.
posure in three areas of China, Food Addit. Contam. 28 (4) (2011) 461–470. [60] S. Mehri, M.A. Meshki, H. Hosseinzadeh, Linalool as a neuroprotective agent
[32] M. Theumer, M. Cánepa, A. López, V. Mary, J. Dambolena, H. Rubinstein, against acrylamide-induced neurotoxicity in Wistar rats, Drug Chem. Toxicol. 38
Subchronic mycotoxicoses in Wistar rats: assessment of the in vivo and in vitro (2) (2015) 162–166.
genotoxicity induced by fumonisins and aflatoxin B 1, and oxidative stress [61] G.M. Morsy, H.H. El Sayed, E.I. Hanna, M.K. Abdel Rahman, Turmeric may protect
418
A. Hosseini, H. Hosseinzadeh Biomedicine & Pharmacotherapy 99 (2018) 411–421
cells from oxidative stress by acrylamide in-vivo, J. Egypt. Soc. Toxicol. (2008) (2013) 664–667.
123–129. [91] G. Flora, D. Gupta, A. Tiwari, Preventive efficacy of bulk and nanocurcumin
[62] S. Ayoob, A.K. Gupta, Fluoride in drinking water: a review on the status and stress against lead-induced oxidative stress in mice, Biol. Trace Elem. Res. 152 (1)
effects, Crit. Rev. Environ. Sci. Technol. 36 (6) (2006) 433–487. (2013) 31.
[63] I. Błaszczyk, E. Grucka-Mamczar, S. Kasperczyk, E. Birkner, Influence of methio- [92] E. Casalino, C. Sblano, G. Calzaretti, C. Landriscina, Acute cadmium intoxication
nine upon the concentration of malondialdehyde in the tissues and blood of rats induces alpha-class glutathione S-transferase protein synthesis and enzyme ac-
exposed to sodium fluoride, Biol. Trace Elem. Res. 129 (1) (2009) 229–238. tivity in rat liver, Toxicology 217 (2) (2006) 240–245.
[64] I. Inkielewicz, J. Krechniak, Fluoride content in soft tissues and urine of rats ex- [93] M.-Y. Kang, S.-H. Cho, Y.-H. Lim, J.-C. Seo, Y.-C. Hong, Effects of environmental
posed to sodium fluoride in drinking water, Fluoride 36 (4) (2003) 263–266. cadmium exposure on liver function in adults, Occup. Environ. Med. 70 (4) (2013)
[65] Y. Shivarajashankara, A. Shivashankara, P.G. Bhat, S.H. Rao, Effect of fluoride 268–273, http://dx.doi.org/10.1136/oemed-2012-101063.
intoxication on lipid peroxidation and antioxidant systems in rats, Fluoride 34 (2) [94] A. El-Mansy, S. Mazroa, W. Hamed, A. Yaseen, E. El-Mohandes, Histological and
(2001) 108–113. immunohistochemical effects of Curcuma longa on activation of rat hepatic stel-
[66] S.F. Nabavi, A.H. Moghaddam, S. Eslami, S.M. Nabavi, Protective effects of cur- late cells after cadmium induced hepatotoxicity, Biotech. Histochem. 91 (3)
cumin against sodium fluoride-induced toxicity in rat kidneys, Biol. Trace Elem. (2016) 170–181.
Res. 145 (3) (2012) 369–374. [95] N. Tarasub, T. Junseecha, C. Tarasub, W.D.N. Ayutthaya, Protective effects of
[67] B. Ali, Agents ameliorating or augmenting experimental gentamicin ne- curcumin, vitamin C, or their combination on cadmium-induced hepatotoxicity, J.
phrotoxicity: some recent research, Food Chem. Toxicol. 41 (11) (2003) Basic Clin. Pharm. 3 (2) (2012) 273.
1447–1452. [96] N. Das, S. Paul, D. Chatterjee, N. Banerjee, N.S. Majumder, N. Sarma, T.J. Sau,
[68] B.H. Ali, A. Za’abi, G. Blunden, A. Nemmar, Experimental gentamicin ne- S. Basu, S. Banerjee, P. Majumder, Arsenic exposure through drinking water in-
phrotoxicity and agents that modify it: a mini‐review of recent research, Basic creases the risk of liver and cardiovascular diseases in the population of West
Clin. Pharmacol. Toxicol. 109 (4) (2011) 225–232. Bengal, India, BMC Public Health 12 (1) (2012) 639.
[69] P. Balakumar, V.A. Chakkarwar, V. Kumar, A. Jain, J. Reddy, M. Singh, [97] L. Hao, J. Zhao, X. Wang, H. Wang, H. Wang, G. Xu, Hepatotoxicity from arsenic
Experimental models for nephropathy, J. Renin-Angiotensin-Aldosterone Syst. 9 trioxide for pediatric acute promyelocytic leukemia, J. Pediatr. Hematol. Oncol.
(4) (2008) 189–195. 35 (2) (2013) e67–e70.
[70] S. Cuzzocrea, E. Mazzon, L. Dugo, I. Serraino, R. Di Paola, D. Britti, A. De Sarro, [98] S. Flora, S. Bhadauria, G. Kannan, N. Singh, Arsenic induced oxidative stress and
S. Pierpaoli, A.P. Caputi, E. Masini, A role for superoxide in gentamicin-mediated the role of antioxidant supplementation during chelation: a review, J. Environ.
nephropathy in rats, Eur. J. Pharmacol. 450 (1) (2002) 67–76. Biol. 28 (2) (2007) 333.
[71] E. Azab, F.A. Fetouh, M.O. Albasha, Nephro-protective effects of curcumin, ro- [99] J. Liu, M.P. Waalkes, Liver is a target of arsenic carcinogenesis, Toxicol. Sci. 105
semary and propolis against gentamicin induced toxicity in guinea pigs: mor- (1) (2008) 24–32.
phological and biochemical study, Am. J. Clin. Exp. Med. 2 (2) (2014) 28–35. [100] Y. Zhang, J.X. Liu, L. Lin, L.Q. Li, Pharmacokinetics of crocin-1 after oral ad-
[72] B.H. El-Zawahry, E.M.A. El Kheir, M. Effat, The protective effect of curcumin ministration in rats, Chin. Pharm. J. 47 (2) (2012) 136–140.
against gentamicin-induced renal dysfunction and oxidative stress in male albino [101] X. Pan, Y. Dai, X. Li, N. Niu, W. Li, F. Liu, Y. Zhao, Z. Yu, Inhibition of arsenic
rats, Egypt. J. Hosp. Med. 29 (2007) 546–556. induced-rat liver injury by grape seed exact through suppression of NADPH oxi-
[73] L. He, X. Peng, J. Zhu, G. Liu, X. Chen, C. Tang, H. Liu, F. Liu, Y. Peng, Protective dase and TGF-β/Smad activation, Toxicol. Appl. Pharmacol. 254 (3) (2011)
effects of curcumin on acute gentamicin-induced nephrotoxicity in rats, Can. J. 323–331.
Physiol. Pharmacol. 93 (4) (2015) 275–282. [102] M.I. Yousef, F.M. El-Demerdash, F.M. Radwan, Sodium arsenite induced bio-
[74] G. Gobe, D. Crane, Mitochondria, reactive oxygen species and cadmium toxicity in chemical perturbations in rats: ameliorating effect of curcumin, Food Chem.
the kidney, Toxicol. Lett. 198 (1) (2010) 49–55. Toxicol. 46 (11) (2008) 3506–3511.
[75] M.M. Brzóska, M. Galażyn-Sidorczuk, J. Rogalska, A. Roszczenko, M. Jurczuk, [103] O. Cakici, E. Akat, Propanil-induced histopathological changes in the liver and
K. Majewska, J. Moniuszko-Jakoniuk, Beneficial effect of zinc supplementation on kidney of mice, Anal. Quant. Cytopathol. Histopathol. 35 (3) (2013) 163–170.
biomechanical properties of femoral distal end and femoral diaphysis of male rats [104] C.A. Otuechere, S.O. Abarikwu, V.I. Olateju, A.L. Animashaun, O.E. Kale,
chronically exposed to cadmium, Chem. Biol. Interact. 171 (3) (2008) 312–324. Protective effect of curcumin against the liver toxicity caused by propanil in rats,
[76] H. Jemai, I. Messaoudi, A. Chaouch, A. Kerkeni, Protective effect of zinc supple- Int. Sch. Res. Notices 2014 (2014).
mentation on blood antioxidant defense system in rats exposed to cadmium, J. [105] Y. Liao, X. Lu, C. Lu, G. Li, Y. Jin, H. Tang, Selection of agents for prevention of
Trace Elem. Med. Biol. 21 (4) (2007) 269–273. cisplatin-induced hepatotoxicity, Pharmacol. Res. 57 (2) (2008) 125–131.
[77] N. Tarasub, C. Tarasub, W.D.N. Ayutthaya, Protective role of curcumin on cad- [106] S. Palipoch, C. Punsawad, P. Koomhin, P. Suwannalert, Hepatoprotective effect of
mium-induced nephrotoxicity in rats, J. Environ. Chem. Ecotoxicol. 3 (2) (2011) curcumin and alpha-tocopherol against cisplatin-induced oxidative stress, BMC
17–24. Complement. Altern. Med. 14 (1) (2014) 111.
[78] C.-H. Lee, S.-W. Park, Y.S. Kim, S.S. Kang, J.A. Kim, S.H. Lee, S.-M. Lee, Protective [107] M.E. Robbins, W. Zhao, C.S. Davis, S. Toyokuni, S.M. Bonsib, Radiation-induced
mechanism of glycyrrhizin on acute liver injury induced by carbon tetrachloride in kidney injury: a role for chronic oxidative stress? Micron 33 (2) (2002) 133–141.
mice, Biol. Pharm. Bull. 30 (10) (2007) 1898–1904. [108] C. Jalili, M.R. Salahshoor, A. Naseri, Protective effect of Urtica dioica L against
[79] H.-S. Lee, L. Li, H.-K. Kim, D. Bilehal, W. Li, D.-S. Lee, Y.-H. Kim, The protective nicotine-induced damage on sperm parameters, testosterone and testis tissue in
effects of Curcuma longa Linn. Extract on carbon tetrachloride-induced hepato- mice, Iran. J. Reprod. Med. 12 (6) (2014) 401.
toxicity in rats via upregulation of Nrf2, J. Microb. Biotechnol. 20 (9) (2010) [109] S. Li, D. Lu, Y. Zhang, Y. Zhang, Long-term treatment of hydrogen-rich saline
1331–1338. abates testicular oxidative stress induced by nicotine in mice, J. Assist. Reprod.
[80] G.-H. Lee, H.-Y. Lee, M.-K. Choi, H.-W. Chung, S.-W. Kim, H.-J. Chae, Protective Genet. 31 (1) (2014) 109–114.
effect of Curcuma longa L. extract on CCl 4-induced acute hepatic stress, BMC Res. [110] A.-R. El-Zayadi, Heavy smoking and liver, World J. Gastroenterol. WJG 12 (38)
Notes 10 (1) (2017) 77. (2006) 6098.
[81] J. Chilakapati, K. Shankar, M.C. Korrapati, R.A. Hill, H.M. Mehendale, Saturation [111] M. Salahshoor, S. Mohamadian, S. Kakabaraei, S. Roshankhah, C. Jalili, Curcumin
toxicokinetics of thioacetamide: role in initiation of liver injury, Drug Metab. improves liver damage in male mice exposed to nicotine, J. Tradit. Complement.
Dispos. 33 (12) (2005) 1877–1885. Med. 6 (2) (2016) 176–183.
[82] V.B. Djordjević, Free radicals in cell biology, Int. Rev. Cytol. 237 (2004) 57–89. [112] Z. Liang, R. Wu, W. Xie, C. Xie, J. Wu, S. Geng, X. Li, M. Zhu, W. Zhu, J. Zhu,
[83] S.M. Salama, M.A. Abdulla, A.S. AlRashdi, S. Ismail, S.S. Alkiyumi, Effects of Curcumin on tobacco smoke- induced hepatic MAPK pathway activation
S. Golbabapour, Hepatoprotective effect of ethanolic extract of Curcuma longa on and epithelial–mesenchymal transition in vivo, Phytother. Res. 31 (8) (2017)
thioacetamide induced liver cirrhosis in rats, BMC Complement. Altern. Med. 13 1230–1239.
(1) (2013) 56. [113] S. Acharya, K. Mehta, S. Krishnan, C.V. Rao, A subtoxic interactive toxicity study
[84] L. Navarro-Moreno, M. Quintanar-Escorza, S. González, R. Mondragón, J. Cerbón- of ethanol and chromium in male Wistar rats, Alcohol 23 (2) (2001) 99–108.
Solorzáno, J. Valdés, J. Calderón-Salinas, Effects of lead intoxication on inter- [114] A.K. Patlolla, C. Barnes, C. Yedjou, V. Velma, P.B. Tchounwou, Oxidative stress,
cellular junctions and biochemical alterations of the renal proximal tubule cells, DNA damage, and antioxidant enzyme activity induced by hexavalent chromium
Toxicol. In Vitro 23 (7) (2009) 1298–1304. in Sprague- Dawley rats, Environ. Toxicol. 24 (1) (2009) 66–73.
[85] S. Flora, Metal poisoning: threat and management, Al Ameen J. Med. Sci. 2 (2) [115] M. Gunaratnam, M.H. Grant, Cr (VI) inhibits DNA, RNA and protein syntheses in
(2009) 4–26. hepatocytes: involvement of glutathione reductase, reduced glutathione and DT-
[86] H.M. Korashy, A.O. El-Kadi, Transcriptional regulation of the NAD (P) H: quinone diaphorase, Toxicol. In Vitro 22 (4) (2008) 879–886.
oxidoreductase 1 and glutathione S-transferase ya genes by mercury, lead, and [116] J. Pourahmad, M. Rabiei, F. Jokar, P.J. O’Brien, A comparison of hepatocyte cy-
copper, Drug Metab. Dispos. 34 (1) (2006) 152–165. totoxic mechanisms for chromate and arsenite, Toxicol. 206 (3) (2005) 449–460.
[87] E.K. Jaffe, J. Martins, J. Li, J. Kervinen, R.L. Dunbrack, The molecular mechanism [117] F. Xiao, X. Feng, M. Zeng, L. Guan, Q. Hu, C. Zhong, Hexavalent chromium induces
of lead inhibition of human porphobilinogen synthase, J. Biol. Chem. 276 (2) energy metabolism disturbance and p53-dependent cell cycle arrest via reactive
(2001) 1531–1537. oxygen species in L-02 hepatocytes, Mol. Cell. Biochem. 371 (1–2) (2012) 65–76.
[88] C.D. Pandya, P.P. Pillai, S.S. Gupta, Lead and cadmium co-exposure mediated [118] S. Kalayarasan, N. Sriram, A. Sureshkumar, G. Sudhandiran, Chromium
toxic insults on hepatic steroid metabolism and antioxidant system of adult male (VI)‐induced oxidative stress and apoptosis is reduced by garlic and its derivative
rats, Biol. Trace Elem. Res. 134 (3) (2010) 307–317. s- allylcysteine through the activation of Nrf2 in the hepatocytes of Wistar rats, J.
[89] C.-M. Liu, J.-Q. Ma, Y.-Z. Sun, Protective role of puerarin on lead-induced al- Appl. Toxicol. 28 (7) (2008) 908–919.
terations of the hepatic glutathione antioxidant system and hyperlipidemia in rats, [119] W.R. García-Niño, E. Tapia, C. Zazueta, Z.L. Zatarain-Barrón, R. Hernández-Pando,
Food Chem. Toxicol. 49 (12) (2011) 3119–3127. C.C. Vega-García, J. Pedraza-Chaverrí, Curcumin pretreatment prevents potassium
[90] S. Baxla, R. Gora, P. Kerketta, N. Kumar, B. Roy, P. Patra, Hepatoprotective effect dichromate-induced hepatotoxicity, oxidative stress, decreased respiratory com-
of Curcuma longa against lead induced toxicity in Wistar rats, Vet. World 6 (9) plex I activity, and membrane permeability transition pore opening, Evid. Based
419
A. Hosseini, H. Hosseinzadeh Biomedicine & Pharmacotherapy 99 (2018) 411–421
Complement. Altern. Med. 2013 (2013). [147] B. Shivasharan, P. Nagakannan, B. Thippeswamy, V. Veerapur, Protective effect of
[120] H. Fieten, P.A. Leegwater, A.L. Watson, J. Rothuizen, Canine models of copper Calendula officinalis L. flowers against monosodium glutamate induced oxidative
toxicosis for understanding mammalian copper metabolism, Mamm. Genome 23 stress and excitotoxic brain damage in rats, Indian J. Clin. Biochem. 28 (3) (2013)
(1–2) (2012) 62–75. 292–298.
[121] J. Pourahmad, P.J. O’Brien, A comparison of hepatocyte cytotoxic mechanisms for [148] R.M. Khalil, N.F. Khedr, Curcumin protects against monosodium glutamate neu-
Cu 2+ and Cd 2+, Toxicology 143 (3) (2000) 263–273. rotoxicity and decreasing NMDA2B and mGluR5 expression in rat hippocampus,
[122] X. Wan, Y. Li, X. Luo, Curcumin attenuated the lipid peroxidation and apoptotic Neurosignals 24 (1) (2016) 81–87.
liver injury in copper-overloaded rats, Zhonghua er ke za zhi= Chin. J. Pediatr. 45 [149] A. Kumar, S. Dogra, A. Prakash, Protective effect of curcumin (Curcuma longa),
(8) (2007) 604–608. against aluminium toxicity: possible behavioral and biochemical alterations in
[123] Y. Nakagawa, T. Suzuki, H. Kamimura, F. Nagai, Role of mitochondrial membrane rats, Behav. Brain Res. 205 (2) (2009) 384–390.
permeability transition in N-nitrosofenfluramine-induced cell injury in rat hepa- [150] P. Sethi, A. Jyoti, E. Hussain, D. Sharma, Curcumin attenuates aluminium-induced
tocytes, Eur. J. Pharmacol. 529 (1) (2006) 33–39. functional neurotoxicity in rats, Pharmacol. Biochem. Behav. 93 (1) (2009) 31–39.
[124] T.S. Poet, A.A. Kousba, S.L. Dennison, C. Timchalk, Physiologically based phar- [151] C. Claverie, R. Corbella, D. Martin, C. Diaz, Protective effects of zinc on cadmium
macokinetic/pharmacodynamic model for the organophosphorus pesticide dia- toxicity in rodents, Biol. Trace Elem. Res. 75 (1) (2000) 1–9.
zinon, Neurotoxicology 25 (6) (2004) 1013–1030. [152] G.M. Abu-Taweel, J.S. Ajarem, M. Ahmad, Protective effect of curcumin on an-
[125] F. El-Demerdash, M. Yousef, F. Kedwany, H. Baghdadi, Role of α-tocopherol and β- xiety, learning behavior, neuromuscular activities, brain neurotransmitters and
carotene in ameliorating the fenvalerate-induced changes in oxidative stress, he- oxidative stress enzymes in cadmium intoxicated mice, J. Behav. Brain Sci. 3 (01)
mato-biochemical parameters, and semen quality of male rats, J. Environ. Sci. (2013) 74.
Health Part B 39 (3) (2004) 443–459. [153] V. Dhar, M. Bhatnagar, Physiology and toxicity of fluoride, Indian J. Dent. Res. 20
[126] P. Lari, M. Rashedinia, K. Abnous, H. Hosseinzadeh, Crocin improves lipid dys- (3) (2009) 350.
regulation in subacute diazinon exposure through ERK1/2 pathway in rat liver, [154] C. Sharma, P. Suhalka, P. Sukhwal, N. Jaiswal, M. Bhatnagar, Curcumin attenuates
Drug Res. 64 (06) (2014) 301–305. neurotoxicity induced by fluoride: an in vivo evidence, Pharmacogn. Mag. 10 (37)
[127] B.M. Razavi, H. Hosseinzadeh, A.R. Movassaghi, M. Imenshahidi, K. Abnous, (2014) 61.
Protective effect of crocin on diazinon induced cardiotoxicity in rats in subchronic [155] G. Ciftci, A. Aksoy, G.F. Yarim, C. Nisbet, D. Guvenc, A. Ertekin, Therapeutic role
exposure, Chem. Biol. Interact. 203 (3) (2013) 547–555. of curcumin in oxidative DNA damage caused by formaldehyde, Microsc. Res.
[128] A.T. Hariri, S.A. Moallem, M. Mahmoudi, H. Hosseinzadeh, The effect of crocin Tech. 78 (5) (2015) 391–395.
and safranal, constituents of saffron, against subacute effect of diazinon on he- [156] Q. Cui, X. Li, H. Zhu, Curcumin ameliorates dopaminergic neuronal oxidative
matological and genotoxicity indices in rats, Phytomedicine 18 (6) (2011) damage via activation of the Akt/Nrf2 pathway, Mol. Med. Rep. 13 (2) (2016)
499–504. 1381–1388.
[129] M. Messarah, W. Amamra, A. Boumendjel, L. Barkat, I. Bouasla, C. Abdennour, [157] S. Wolf, D. Barton, L. Kottschade, A. Grothey, C. Loprinzi, Chemotherapy-induced
M.S. Boulakoud, A.E. Feki, Ameliorating effects of curcumin and vitamin E on peripheral neuropathy: prevention and treatment strategies, Eur. J. Cancer 44 (11)
diazinon-induced oxidative damage in rat liver and erythrocytes, Toxicol. Ind. (2008) 1507–1515.
Health 29 (1) (2013) 77–88. [158] N. Greeshma, K. Prasanth, B. Balaji, Tetrahydrocurcumin exerts protective effect
[130] T. Szkudelski, The mechanism of alloxan and streptozotocin action in B cells of the on vincristine induced neuropathy: behavioral, biochemical, neurophysiological
rat pancreas, Physiol. Res. 50 (6) (2001) 537–546. and histological evidence, Chem. Biol. Interact. 238 (2015) 118–128.
[131] O.M. Abo- Salem, G.I. Harisa, T.M. Ali, E.S.M. El- Sayed, F.M. Abou- Elnour, [159] R.E. Heikkila, P.K. Sonsalla, The MPTP-treated mouse as a model of parkinsonism:
Curcumin ameliorates streptozotocin‐induced heart injury in rats, J. Biochem. how good is it? Neurochem. Int. 20 (1992) 299–303.
Mol. Toxicol. 28 (6) (2014) 263–270. [160] R.L. Jayaraj, N. Elangovan, K. Manigandan, S. Singh, S. Shukla, CNB-001 a novel
[132] S. Imbaby, M. Ewais, S. Essawy, N. Farag, Cardioprotective effects of curcumin and curcumin derivative, guards dopamine neurons in MPTP model of Parkinson’s
nebivolol against doxorubicin-induced cardiac toxicity in rats, Hum. Exp. Toxicol. disease, Biomed. Res. Int. 2014 (2014).
33 (8) (2014) 800–813. [161] A.P. Kudin, T.A. Kudina, J. Seyfried, S. Vielhaber, H. Beck, C.E. Elger, W.S. Kunz,
[133] E.M. El-Sayed, A.S.A. El-azeem, A.A. Afify, M.H. Shabana, H.H. Ahmed, Seizure- dependent modulation of mitochondrial oxidative phosphorylation in rat
Cardioprotective effects of Curcuma longa L. extracts against doxorubicin-induced hippocampus, Eur. J. Neurosci. 15 (7) (2002) 1105–1114.
cardiotoxicity in rats, J. Med. Plants Res. 5 (17) (2011) 4049–4058. [162] H. Kaur, A. Bal, R. Sandhir, Curcumin supplementation improves mitochondrial
[134] T. Sagiroglu, M. Kanter, M.A. Yagci, A. Sezer, M. Erboga, Protective effect of and behavioral deficits in experimental model of chronic epilepsy, Pharmacol.
curcumin on cyclosporin A-induced endothelial dysfunction, antioxidant capacity, Biochem. Behav. 125 (2014) 55–64.
and oxidative damage, Toxicol. Ind. Health 30 (4) (2014) 316–327. [163] M.-H. Ji, L.-L. Qiu, J.-J. Yang, H. Zhang, X.-R. Sun, S.-H. Zhu, W.-Y. Li, J.-J. Yang,
[135] R. Mehdizadeh, M.R. Parizadeh, A.-R. Khooei, S. Mehri, H. Hosseinzadeh, Pre-administration of curcumin prevents neonatal sevoflurane exposure-induced
Cardioprotective effect of saffron extract and safranal in isoproterenol-induced neurobehavioral abnormalities in mice, Neurotoxicology 46 (2015) 155–164.
myocardial infarction in Wistar rats, Iran. J. Basic Med. Sci. 16 (1) (2013) 56. [164] E. Dybing, P. Farmer, M. Andersen, T. Fennell, S. Lalljie, D. Müller, S. Olin,
[136] M. Nazam Ansari, U. Bhandari, K. Pillai, Protective role of curcumin in myocardial B. Petersen, J. Schlatter, G. Scholz, Human exposure and internal dose assessments
oxidative damage induced by isoproterenol in rats, Hum. Exp. Toxicol. 26 (12) of acrylamide in food, Food Chem. Toxicol. 43 (3) (2005) 365–410.
(2007) 933–938. [165] S. Mehri, K. Abnous, A. Khooei, S.H. Mousavi, V.M. Shariaty, H. Hosseinzadeh,
[137] S. Rahoui, Y. Martinez, L. Sakouhi, C. Ben, M. Rickauer, E. El Ferjani, Crocin reduced acrylamide-induced neurotoxicity in Wistar rat through inhibition
L. Gentzbittel, A. Chaoui, Cadmium-induced changes in antioxidative systems and of oxidative stress, Iran. J. Basic Med. Sci. 18 (9) (2015) 902.
differentiation in roots of contrasted Medicago truncatula lines, Protoplasma 254 [166] S. Mehri, K. Abnous, S.H. Mousavi, V.M. Shariaty, H. Hosseinzadeh,
(1) (2017) 473–489. Neuroprotective effect of crocin on acrylamide-induced cytotoxicity in PC12 cells,
[138] U. Kukongviriyapan, P. Pannangpetch, V. Kukongviriyapan, W. Donpunha, Cell. Mol. Neurobiol. 32 (2) (2012) 227–235.
K. Sompamit, P. Surawattanawan, Curcumin protects against cadmium-induced [167] S.N. Prasad, Neuroprotective effect of geraniol and curcumin in an acrylamide
vascular dysfunction, hypertension and tissue cadmium accumulation in mice, model of neurotoxicity in Drosophila melanogaster: relevance to neuropathy, J.
Nutrients 6 (3) (2014) 1194–1208. Insect Physiol. 60 (2014) 7–16.
[139] A. Nemmar, D. Subramaniyan, B.H. Ali, Protective effect of curcumin on pul- [168] D.M. Samy, C.A. Ismail, R.A. Nassra, T.M. Zeitoun, A.M. Nomair, Downstream
monary and cardiovascular effects induced by repeated exposure to diesel exhaust modulation of extrinsic apoptotic pathway in streptozotocin-induced Alzheimer’s
particles in mice, PLoS One 7 (6) (2012) e39554. dementia in rats: erythropoietin versus curcumin, Eur. J. Pharmacol. 770 (2016)
[140] C. Kalpana, K. Rajasekharan, V.P. Menon, Modulatory effects of curcumin and 52–60.
curcumin analog on circulatory lipid profiles during nicotine-induced toxicity in [169] C. Prakash, M. Soni, V. Kumar, Mitochondrial oxidative stress and dysfunction in
Wistar rats, J. Med. Food 8 (2) (2005) 246–250. arsenic neurotoxicity: a review, J. Appl. Toxicol. 36 (2) (2016) 179–188.
[141] M. Chakraborty, J.V. Kamath, A. Bhattacharjee, Pharmacodynamic interaction of [170] P. Sankar, A.G. Telang, R. Kalaivanan, V. Karunakaran, S. Suresh, M. Kesavan,
green tea extract with hydrochlorothiazide against cyclophosphamide-induced Oral nanoparticulate curcumin combating arsenic-induced oxidative damage in
myocardial damage, Toxicol. Int. 21 (2) (2014) 196. kidney and brain of rats, Toxicol. Ind. Health 32 (3) (2016) 410–421.
[142] M. Chakraborty, A. Bhattacharjee, J.V. Kamath, Cardioprotective effect of cur- [171] M. Waseem, S. Parvez, Neuroprotective activities of curcumin and quercetin with
cumin and piperine combination against cyclophosphamide-induced cardiotoxi- potential relevance to mitochondrial dysfunction induced by oxaliplatin,
city, Indian J. Pharmacol. 49 (1) (2017) 65. Protoplasma 253 (2) (2016) 417–430.
[143] M.S. Al Moundhri, S. Al-Salam, A. Al Mahrouqee, S. Beegam, B.H. Ali, The effect of [172] A. Mehta, R.S. Verma, N. Srivastava, Chlorpyrifos induced alterations in the levels
curcumin on oxaliplatin and cisplatin neurotoxicity in rats: some behavioral, of hydrogen peroxide, nitrate and nitrite in rat brain and liver, Pestic. Biochem.
biochemical, and histopathological studies, J. Med. Toxicol. 9 (1) (2013) 25–33. Physiol. 94 (2) (2009) 55–59.
[144] M. Kamyar, B.M. Razavi, F.V. Hasani, S. Mehri, A. Foroutanfar, H. Hosseinzadeh, [173] S. Hassani, M. Sepand, A. Jafari, J. Jaafari, R. Rezaee, M. Zeinali, F. Tavakoli,
Crocin prevents haloperidol-induced orofacial dyskinesia: possible an antioxidant K. Razavi-Azarkhiavi, Protective effects of curcumin and vitamin E against
mechanism, Iran. J. Basic Med. Sci. 19 (10) (2016) 1070. chlorpyrifos-induced lung oxidative damage, Hum. Exp. Toxicol. 34 (6) (2015)
[145] M. Bishnoi, K. Chopra, S.K. Kulkarni, Protective effect of curcumin, the active 668–676.
principle of turmeric (Curcuma longa) in haloperidol-induced orofacial dyskinesia [174] N. Venkatesan, Pulmonary protective effects of curcumin against paraquat toxi-
and associated behavioural, biochemical and neurochemical changes in rat brain, city, Life Sci. 66 (2) (1999) PL21–PL28.
Pharmacol. Biochem. Behav. 88 (4) (2008) 511–522. [175] K.R. Devi, M. Mosheraju, K.D. Reddy, Curcumin prevents chromium induced
[146] E. Farombi, O. Onyema, Monosodium glutamate-induced oxidative damage and sperm characteristics in mice, IOSR J. Pharm. 2 (2012) 312–316.
genotoxicity in the rat: modulatory role of vitamin C, vitamin E and quercetin, [176] K.R. Dev, K. Yadamma, K.D. Reddy, Protective effects of curcumin in cyclo-
Hum. Exp. Toxicol. 25 (5) (2006) 251–259. phosmphamide induced sperm head abnormalities in male mice, Int. J. Pharm.
420
A. Hosseini, H. Hosseinzadeh Biomedicine & Pharmacotherapy 99 (2018) 411–421
421