RESEARCH ARTICLE Dihydroartemisinin-stimulated Widening of the Caliber of Blood Vessels of the Coronary Circulation in Rats

Utoh Nedosa U A1*, Akah P A2, Nedosa K S3, Onyedibe I K4, Nedosa I V5, Agbata C A1, Okoye T C2, Njoku G6
Abstracts: Dihydroartemisinin (DHA) has been shown to be efficacious and rapid in malaria parasite clearance and malaria treatment. The discovery that dihydroartemisinin has anticancer effects suggested that dihydroartemisinin may have other beneficial or adverse systemic effects. We investigated the effects of dihydroartemisinin on the heart of Wistar albino fats.. The effects of four dosages of oral dihydroartemisinin on the heart of Wistar albino rats were investigated. The dosages of DHA administered were 1mg/kg, 2mg/kg, 60mg/kg and 80mg/kg. In a fifth experiment, the 1mg/kg dosage of DHA was administered twice to a group of rats with a one week period of rest between the two administrations. The results of the study showed that DHA produced dose, repetition and time dependent increases in the caliber of the blood vessels of the coronary circulation. These findings suggest that dihydroartemisinin might be useful for the management of myocardial infarction, congestive heart failure, angina pectoris and other conditions involving narrowing of coronary arteries. Key Words: Dihydroartemisinin, Widening, Caliber, Coronary blood vessels INTRODUCTION Dihydroartemisinin produces efficacious schizonticidal action on malaria parasites in clinical uncomplicated and severe malaria 5, 9. The efficacy of artemisinin combination therapies in the elimination of malaria clinical symptoms caused the world health organization to approve their use for the treatment of complicated and uncomplicated malaria in Africa. In clinical malaria, the malaria parasites are located in the erythrocytes of the blood. The heart is at the center of the circulatory system. This study therefore investigated the effects of oral dihydroartemisinin treatment on the heart. MATERIALS AND METHODS The study examined the histological effects of dihydroartemisinin on the heart of Wistar albino rats. Five dosages of dihydroartemisinin (DHA) were given by oral intubation to 5 groups of Wistar albino rats (5 in each
1Dept.

RESULTS The results of the study showed that oral dihydroartemisinin treatment caused dose, repetition and time dependent widening of the blood vessels of the coronary circulation (fig. 1-9) in comparism with those of control rats [fig. 10]. These include the two coronary arteries; the arteriosinusoidal vessels that connect arterioles to the heart chambers; thebesian veins that connect capillaries to the heart chambers; arterio-luminal vessels which are small arteries that drain directly into the chambers and the anastomoses between the coronary arterioles and the extra cardiac arterioles especially around the mouths of the great veins (figure .1-9). DISCUSSIONS Oxygen required for the functioning of the cells of the body are transported in the blood in the form of oxy-haemoglobin (haemoglobin is carried by the red blood cells). Heart muscle contraction produces sequential changed that result in changes in pressures and flows in the heart chamber and the blood vessels all over the body1. It is the efficient pumping action of the heart muscles that drives the blood round the human body. Thus the heart muscles themselves need sufficient supply of oxygen to be able to function optimally. Such efficient supply of oxygen to the heart muscles is only possible if the lumen of the blood vessels of the coronary circulation are wide enough to permit the supply of enough oxygen for heart muscle cellular energy generation. The heart muscle, like the skeletal muscle, compresses its blood vessels when it contracts1. Thus dihydroartemisinin effect of widening of the blood vessels of the coronary circulation will result in increased blood flow to the heart muscles and consequent increase in the amount of oxygen (carried in red blood cells) delivered to the myocardium. CONCLUSIONS When the blood flow to the heart is interrupted for more than a few minutes, important changes occur in the myocardium that lead to irreversible changes and death of the cardiac muscle cells (myocardial infarction) 1. When flow through a coronary artery is reduced to the point that the myocardium that it supplies becomes hypoxic, angina pectoris develops due to the accumulation of P factor 1 . Oral dihydroartemisinin has been shown to produce effects on systemic organs other than the heart 10 .The widening effects of oral Dihydroartemisinin seen in the results of this study suggest that oral dihydroartemisinin might be useful in the relief of angina pain and in the treatment of myocardial infarction. REFERENCES AND NOTES
1. William Ganong. (1997).Review of Medical Physiology (18 th Ed) .Appleton & Lange.

group) and the equivalent dosages of distilled water were given to the control groups (4 in each group). The dosages of DHA and distilled water were: 2mg/kg (day1), 1mg/kg (day 2-5) 2mg/kg (day 1), 1mg/kg (day 2-5) repeated after an interval of 1 week. 2mg/kg DHA (day 1-5) 60mg/kg DHA (day 1-5) 80mg/kg DHA (day 1-5) Adult albino rats weighing 106-140 grams were used in experiments 1, 3, 4 and 5. Young adult albino rats weighing 75-90 grams were used in experiment 2. The Data Collection The DHA- treated and control rats were sacrificed 24 hours after the administration of the last dose of DHA or distilled water. The heart of the sacrificed DHA-treated and control rats were harvested and prepared for histological examination. The severed test and control hearts were fixed in 10% buffered formalin. Thereafter they were dehydrated progressively in 70%, 80%, 90%, 95% and absolute alcohol. They were then cleared with xylene, impregnated in paraffin wax and embedded in mounting paraffin wax on a wooden block. Excess paraffin was trimmed from the organ to expose the surface for micro sectioning. A portion of the organ (the heart) was prepared for sectioning. The micro sectioning of the heart was done with a Rotary microtome machine and its processing was done in an Automatic Shaidon Ellich Duplex processor for 18 to 24 hours. The processed micro sections of the heart were then stained with Coles Haematoxylene and Eosin stain and left for a few days to dry. The dried stained slides of the micro sections of the heart were then photographed with a RICOH Micrographic Camera attached to a Nicon Graphic camera. The photomicrographs which resulted were examined histologically.

of Pharmacology and Toxicology, Nnamdi Azikiwe University, P. M. B. 5025, Awka, Anambra State, Nigeria. E-mail: unedosa@yahoo.com *Corresponding author
2Dept.

of Pharmacology and Toxicology, University of Nigeria, Nsukka, Enugu State, Nigeria.

3Evangelical

Churches of West Africa Hospital (ECWA), Egbe, P. M. B.,202, Kogi State,Nigeria.

4Department

of Medical Microbiology, University of Jos Teaching Hospital, P.M. B. 2076, Jos, Plateau State, Nigeria.
5Department

of Industrial Microbiology, Federal University of Technology, Owerri, Imo State, Nigeria.

6Medical

Instructional Unit of Jos Teaching Hospital, P.M. B. 2076, Jos, Plateau State, Nigeria.

Inventi Rapid: Molecular Pharmacology Vol. 2011, Issue 4 [ISSN 0976-3856]

2011pmp100, CCC: $10 Inventi Journals (P) Ltd Published on Web 06/10/2011, www.inventi.in

RESEARCH ARTICLE

Figure(1)

Figure(2)

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Figure(4)

Figure(5)

Figure(6)

Figure(7)

Figure(8)

Figure 1-8 : Photomicrographs of the heart of oral DHA-treated rats showing the widening of the caliber of the blood vessels that supply the heart by the effect of dihydroartemisinin treatment

Figure 9: Photomicrograph of the heart of a control Rat which does not show increased circumference of coronary blood vessels.
2. World Health Organization. (19941995).The role of artemisinin and its derivatives in the current treatment of malaria (WHO/ MAL/ 94. 1067), WHO, Geneva. 3. Cumming J. N., Ploypradith P. Posner G. H. (1997). Antimalarial Activity of Artemisinin (qinghaosu) and related Trioxanes: mechanisim of action. Adv.9 Pharmacol, 37:253-297 [Pub Med]. 4. Asawamahaskda W., Ittratt I. Pu Y-m, Ziffer H. and Meshnick S. R. (1994).Reaction of antimalarial endoperoxides with Specific Parasite Proteins. Antimicrob. Agents Chemother. 38:1854-1858 [PubMed].

Inventi Rapid: Molecular Pharmacology Vol. 2011, Issue 4 [ISSN 0976-3856]

2011pmp100, CCC: $10 Inventi Journals (P) Ltd Published on Web 06/10/2011, www.inventi.in

RESEARCH ARTICLE
5. MHTML. (2008).THE USE OF ANTIMALARIAL DRUGS.Part II: 1.8.Artemisinin And Its Derivatives mht MHTML Document 9/19/2008.Ahsan Manan Khan Bhutta Internet Explorer. 6. Adis Data Information BV. (2004). Antimalarial Drug Toxicity: A Review.Drug Safety.27 (1):2561, Taylor, W Robert J 12; White, Nicholas J 34. 7. Purcel, Katherine.(2004 ).WHO Approves Artemisinin for Malaria in Africa.HerbalGram 2004;64 : 19-20.American Botanical Council. 8. The world Health Organisation Roll Back Malaria Infosheet, Facts on ACTs (ArtemisininBased Combination Therapies), An update on recent progress in Policy and Access to treatment, Available at http/www. rbm. who. Int /cmc-Upload /0/ 000 / 015 /364/RBM Infosheet 9. Htm Accessed July 20, 2004. 9. Meshnick S.R., Taylor T.E. and Kamchonwongpaisan P. (1996). Artemisinin and the antimalaria endoperoxides: From herbal remedy to targeted chemotherapy, Microbiol Rev.vol. 60 (2):301-315. 10. Utoh-Nedosa Uchechukwu A., Njoku Goddy, Nedosa Kenechi S., Akah, Peter A, Ojemudia Theophilus I . and Anowi Chinedu F.(2011). Respiratory Tract- Widening Effects of Dihydroartemisinin in Wistar albino rats, American Journal of Pharmacology and Toxicology 6 (2): 46-48.

Inventi Rapid: Molecular Pharmacology Vol. 2011, Issue 4 [ISSN 0976-3856]

2011pmp100, CCC: $10 Inventi Journals (P) Ltd Published on Web 06/10/2011, www.inventi.in