USE OF HEPAGEN® IN THE DAIRY COW DURING THE

TRANSITION PERIOD: PRACTICAL EXPERIENCES

Tradotto da:
ATTI dell’11° Congresso Multisala SIVAR
Palazzo Trecchi - Cremona - Italia
1 8-9 maggio 2009
USE OF HEPAGEN® IN THE DAIRY COW DURING THE
TRANSITION PERIOD: PRACTICAL EXPERIENCES

Federico Gorrieri1 - Pier Giorgio Persona2

1
DMV LP, Reggio Emilia - 2 DMV, Fatro

INTRODUCTION

During the transition period, conventionally subdivided into close-up (three weeks
before calving) and fresh-cow (three weeks after calving), the dairy cow encounters
deep metabolic changes that can damage its state of health, and its future milk
production, as well as its reproductive career. In particular, the Negative Energy
Balance which takes place at the onset of the milk production, causes rapid fatty
mobilization, which on the one hand guarantees sufficient amounts of energy for
the production of milk but, on the other, causes a high concentration of NEFA in
the blood, and consequently accumulation in the liver, inducing fat infiltration and,
consequently, a reduction in the detoxifying and synthesising functions of the liver.
The consequences of this hepatic lipidosis manifest themselves very early in the post-
partum, appearing as placental retention, metritis, ketosis, abomasum displacement
and mastitis.
To prevent fatty infiltration of the liver, different strategies can be adopted regarding
the diet of the cow in the last stage of lactation, during the dry-off period and
the close-up period and also management of the groups of animals at the various
productive stages.
Inside this complex mechanism, the complementary use of a molecule named
phenoxy-2-methyl-2-propionic acid (Hepagen®) becomes interesting, whose
action, from a biochemical point of view is the activation of PPAR-α (peroxisome
proliferator activated receptor-α), which plays a fundamental role as a regulator of
energy homeostasis in cases of fatty liver syndrome and metabolic pathologies.
More specifically, this receptor has been identified as a regulator of the transcription
of certain genes participating in lipid catabolism, in the transportation of fatty acids
and their entry into the hepatocytes. Recent studies have investigated the possibility
that the NEFA can be oxidized into peroxisomes, small sub-cellular bodies present
in many body tissues; in particular, it seems that peroxisomal ß-oxidation, involves
a greater energy production than that in the mitochondria, which is not under the
control of the energy requirements of the cells; therefore, peroxisomal ß-oxidation
can represent a good pathway for the oxidation of an excess of fatty acids derived
from massive lipomobilisation.
2
 ß-oxidation in the peroxisomes has also been demonstrated in cattle; in particular it
seems that oxidation of around 50% of the NEFA takes place in peroxisomes, and
with no limitations caused by a deficiency of carnitine, essential for the entry of fatty
acids into the mitochondria.5
The consequences of the activation of PPAR-α are increased mitochondrial activity,
greater peroxisomal ß-oxidation and high hepatic gluco-neogenesis, and therefore a
reduced accumulation of triglycerides in the hepatocytes, with, as a consequence, a
recovery of liver functions and an increase in energy production.
The aim of this trial is an evaluation of the effects of Hepagen® after its administration
during the transition period in the dairy cow, considering certain clinical and
productive parameters, such as pathologic post-partum dysmetabolisms, ketosis,
milk production, % of milk protein and fat and fertility rate.

MATERIALS and METHODS

For the trial, starting from May 2008, 200 dairy cows were recruited belonging
to a herd located in the “Pianura Padana”, in Northern Italy, producing milk for
transformation into the typical Parmigiano-Reggiano cheese; on the basis of the
herd number, the animals were subdivided into two groups of 100 head each: even
numbers - treated group, odd numbers - control group.
Each group consisted of cows clinically in a good state of health at the time of
assignment to the group and were subdivided as follows: 1/3 primiparous, 1/3 second
calving and 1/3 multiparous.
The recruited animals were fed on the same diet throughout the trial and were
kept under the same environmental conditions, considering their productive and
reproductive stage.
The animals included in the experimental trial calved between June and August
2008.
The protocol consisted of a double administration of 50 ml of Hepagen® / per head;
the first administration was given 20 days before the expected date of calving, while
the second injection was given on the day of calving; the control group did not receive
any treatment.
The evaluation of the BCS of the animals was routinely performed in the herd and
was performed by assigning a score between 1 and 5.
The ketosis evaluation was run on a random sample of 20 animals from each group
through the use of reactive strips available on the market (Ketolac BHB’- Intervet)4;
moreover, at the same time, the percentage milk fat was also determined.
Data collection regarding production was performed on the basis of the tabulated
monthly functional controls performed by the APA (Local Breeders Association),
while the analysis of fertility was conducted through the management data base for
each herd.

3

Table 1: Post-partum pathologies -
comparison between the two groups.
∗χ2 > 2,71: P > 90%
**χ2 > 3,84: P > 95%
RESULTS and DISCUSSION
A) Post-partum pathologies
The average time of injection in the treated group were the follows: the animals
received the first injection 19.7 days before the real calving date: in particular for
the primiparous it was 20.25 days, for the secondiparous 17.48 days and for the
multiparous 19.48 days.
In the treated group the following pathologies were detected:
1. Primiparous: 4 cases of primary puerperal metritis and 2 cases of puerperal metritis
secondary to dystocia and 2 cases of abomasum displacement.
2. Second calving: 2 cases of primary puerperal metritis and 1 case of puerperal
metritis secondary to placental retention; 1 case of placental retention without the
onset of metritis.
3. Pluriparous: 2 cases of primary puerperal metritis and 1 case of puerperal metritis
secondary to placental retention (one of these due to a three-calf parturition).
No cases of paresis, or milk fever, before or after calving were detected in either
group.
On the basis of the data collected, it appears evident that the treated animals were less
affected by post-partum pathologies than control group.
Pathology Treated Control χ2
(entire group) (entire group)
Primary metritis 8 15 3.26*
Placental Retention + metritis 3 11 5.8**
Metritis secondary to dystocic
calving 2 2 0
Abomasum displacement 2 2 0
In particular, double incidence of post-partum pathologies was recorded in the
animals belonging to the control group, and this is perfectly in accordance with
results reported in previous trials.
More specifically, an analysis of the data subdivided on the basis of the number of
lactations clearly shows that there are no differences between primiparous animals
regardless of the group; on the contrary, the untreated elder animals suffered a
higher frequency of puerperal metritis and placental retention in comparison to those
belonging to the treated group, and the recorded frequency is higher with the increase
in the number of calving.
This difference in the animals after two or more calving can be explained as a greater
in adapting to the metabolic changes in the pre-calving period, probably linked to
previous pathologies also involving the liver; the better results showed by the animals
belonging to the treated group can be attributed to the beneficial effects of phenoxy-
2-methyl-2-proprionic acid on liver function and, in general on digestive function.
Lipid metabolism can compromise the immunological capacity of the cow: the
pathogenesis of placental retention and puerperal metritis certainly involves an
alteration to leukocyte migration, metabolic disorders and hormonal upsets, all
factors strictly connected to the liver function.
4
 B) Ketosis
The evaluation of ketosis was conducted through the use of reactive strips available
on the market (Ketolac BHB® - Intervet), on 20 animals from each group, randomly
chosen every week; this diagnostic kit detects the presence in milk of 13-hydroxy-
butyrate.
Results were of 0,35 mg / dl as an average value for the treated group and 0,86 mg/
dl for the control group; it is interesting to note the positive frequency to the test
recorded in the groups: 10% for the treated group and 25% for the control group. In
the literature, the reference values for concentrations of 13-hydroxy-butyrate in milk
for healthy dairy cows are less than 1 mg /dl, values between 1 and 2 mg / dl for cows
affected by sub-clinical ketosis and between 2 and 10 mg / dl in cases of animals
suffering from clinical ketosis.
The mean values recorded in the two groups clearly differ, although the values
recorded are low, but this is in accordance with the historical data of the herd, where
clinical cases of ketosis have never been a problem. These data are also in accordance
with results from other previous trials, stating that preventive administration of
phenoxy-2-methyl-2-propionic acid permitted a reduction in the frequency of sub-
clinical ketosis.

C) Fat content in milk

An analysis to establish the percentage of fat in the milk was carried out during
the first 5-7 days of milking after calving, on all the recruited cows. The recorded
values are expressed as a mean percentage ± standard deviation; treated primiparous
3,81 ± 0,94, control primiparous 3,96 ± 1,02; secondiparous treated 3,99 ± 1,36,
secondiparous controls 4,14 ± 1,77; treated pluriparous 3,93 ± 0,93, pluriparous
controls 4,40 ± 1.
It was clear that the treated animals have a lower milk fat content than control
animals: considering that the udder is the usual site for lipogenesis during the
peak lactation and that the concentration of fatty acids depends on the lactation
stage and lipomobilisation, this could indicate that the treated animals show lower
lipomobilisation than control animals, probably due to a better utilization of the
NEFA already circulating.

D) BCS
The determination of BSC involved all the animals included in the experimental trial,
but the data were processed only for the cows at the second or later calving, because
for primiparous animals, obviously, BSC data from the period before calving were
not available.
From an analysis of these data, no significant differences were noted between the
treated and control groups; among the treated groups, 4 cows lost ≥ 0.5 BCS points
from the start of drying-off to calving, while in the control group 8 cows lost ≥ 0,5 BSC
points during the same period; in both groups, these cows were the ones which later
suffered post-partum pathologies.
This can be explained by the fact that the great lipomobilisation which took place in
these cows produced direct consequences on the liver, altering correct function in this
organ and producing direct consequences for the post-partum.
5
E) Fertility
The analysis of fertility in the animals included in the experimental trial concerned
the calving-1st A.I. and the calving-conception intervals and the values recorded were
expressed as mean data ± standard deviation.
Calving-1st A.I. interval: globally, the animals belonging to the treated group had a
mean value of 60,26 ± 15,96 days, while the animals belonging to the control group
showed a value of 60,85 ± 16,04.
Considering the animals in terms of the number of lactations, the following data
were obtained: treated primparous: 60,68 ± 17,94 days, primiparous controls 55,48
± 14,22; treated secondiparous 61,7 ± 15,06, secondiparous controls 64,79 ± 17,22;
treated pluriparous 54,85 ± 13,19, pluriparous controls 64,38 ± 15,89.
A global analysis of the calving - 1st A.I. interval shows that for both groups the
first A.I. was practically the same, because both groups formed part of the same
herd and they were taken into the trial under the same management conditions (e.g.
heat detection) and environmental conditions (e.g. feed); in particular, primiparous
controls had an calving - 1st A.I. interval which was better than that in treated animals,
while both treated secondiparous animals and multiparous animals showed clearly
better values than the controls.
Calving - conception interval: globally, the animals belonging to the treated group
showed values of 76,39 ± 27,72, while the animals of the control group had a mean
value of 89,07 ± 33,84.
The calving - conception interval was always in favour of the treated animals rather
than the controls, considering the two groups globally and analysing the value in
relation to the number of lactations. Moreover, this parameter also tends to improve
the higher the number of lactations.

F) Production
The analysis of milk production in kg, protein and fat, was conducted taking the
values recorded by the monthly control on function run by the APA (Local Breeders
Association): lactations were compared with each other and with an equivalent
mature cow.
Both groups, treated and controls, had a production of around 10 tons, with a content
of 3.4 % protein and 3.5 % fat; after data processing, no statistically-significant
differences were recorded.

Milk production
31
1st control
29 2nd control
27
milk produced in kg

25

23

21

19

17

15
1T 1C 2T 2C 3+T 3+C
1st control 23,41 24,06 28,39 24,09 27,53 26,7
2nd control 23,07 25,21 24,43 24,09 30,26 25,1

6
 CONCLUSIONS

Over the last decade, the management of the transition period in dairy cows has been
extensively discussed, especially as regards the relevance that this period has on the
state of health and on production, as well as on the profitability of the reared cows.
The greatest care possible must be given to cows experiencing this phase in terms of
quality and quantity of food and water, as well as suitable facilities for preparation of
calving and an absence of environmental stressors.
Many scientific articles have been written about the importance (in economic terms
or lack of profitability) which one or more pathologies which appear at calving
could have, but these have their roots in a non-optimal management of the previous
lactation and/or drying-off and pre-calving periods.
The costs of post-partum pathologies can be divided into direct costs, linked to the
fees for veterinarians and the use of drugs, and indirect costs, linked to the wasted
milk or the lower quantity of the milk produced, to an increase in the number of open
days, or to possible death, culling or imposed slaughter of the same animal.
From this control case-study, it can be stated that preventive treatment before calving
with phenoxy-2-methyl-2-propionic acid (Hepagen®), was able to improve the calving
- conception interval as well to reduce the incidence of port-partum pathologies, in
animals which were taken under the same dietary and environmental conditions.
It is no less interesting to note that rearing establishments with modern management
systems can, during the transition period which is the key phase as regards both
reproductive and productive aspects, successfully implement corrective preventive
and metabolic actions which reduce the risk and severity of pathologies, the discomfort
of the animals and, at the same time, increase the profitability of the dairy herd.
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