الفهرس 
The liverOnly 14 pages are availabe for public view
 |  | from | 283 |  |  |
| | | from | 283 | | |
Abstract
Epilepsy is not a disease, but a syndrome of different
cerebral disorders of the Central Nervous System (CNS)
which is characterized by excessive discharges of large
numbers of neurons. It is a common neurological
disorder worldwide. Valproate (VPA) is a widely used
drug for treatment of epileptic seizures. Hepatic toxicity
is a hallmark adverse reaction to sodium valproate
(VPA). The present study was designed to explore the
hepatoprotective efficacy of Moringa oleifera leaves
extract on liver toxicity induced by sodium valproate in
adult rats. A number of Adult Sprague-Dawley rats
weighing (120- 150 g) were used. The animals were
divided into five groups, each with 24 animals, 8 rats per
cage as in the following design:
Group1 :(Control) group received 1ml/100 g b.wt of
vehicle (2% tween 80 in water) daily.
group 2 (VPA): Sodium valproate- treated group in
which the rats were treated orally with sodium valproate
(500 mg/kg b.wt / day) for 6 weeks for induction of
chronic hepatotoxicity.group 3 (MO+VPA): Rats received orally Moringa
leaves extract (500 mg/kg b.wt /day) along with sodium
valproate (500 mg/kg b.wt / day) for 6 weeks.
group 4 (MEPA+ VPA): Rats received orally Mepacure
(21.6 mg/kg b.wt / day) along with sodium valproate
(500 mg/kg b.wt / day) for 6 weeks.
group 5 (MO+MEPA+VPA): Rats received orally
Moringa leaves extract (500 mg/kg b.wt/ day) along with
Mepacure (21.6 mg/kg b.wt / day) along with sodium
valproate (500 mg/kg b.wt/ day) for 6 weeks.
In all treatments described in this study, drugs were
prepared in water containing 2% tween 80 and the
appropriate dose of each drug was administered orally by
gastric intubations to each rat daily for six weeks.
Patches of 8 rats from each group were decapitated at
the end of the 2nd, 4th and 6th week of the study. Blood
samples were collected for measuring the biochemical
parameters; Total protein, activities of alanine
transaminase (ALT), aspartate transaminase (AST),
Gamma-Glutamyltransferase (γ-GT) and (Proinflammatory
cytokines) Tumor Necrosis Factor alpha
(TNF-α) were detected. Liver samples were quickly removed from each animal. One part was removed and
immediately immersed in 10% buffered formalin for
histopathological examinations. The second part was
homogenized and the supernatant was used for
determination of oxidative stress and antioxidant
parameters; reduced glutathione (GSH), oxidized
glutathione (GSSG), malondialdehyde (MDA) and nitric
oxide (NO) and the third portion was immediately snap
frozen in liquid nitrogen and then stored at -80°C for the
evaluation of gene expression of Bax and Bcl2.
The results of the present study were as follow:
1- The oral administration of sodium valproate (VPA)
during the time course of the experimental periods (2, 4
and 6 weeks) induced a significant increase in ALT, AST
and GGT activity, with a noticeable decrease in total
protein content. Also, sodium valproate induced a
significant (P<0.05) elevation in (TNF-α) level in a time
dependent manner compared with their respective control
group. In addition, VPA increased levels of hepatic
GSSG, MDA, and NO and decreased levels of GSH.
Furthermore, VPA provoked apoptotic response through
increasing gene expression of pro-apoptotic Bax and decreasing gene expression of anti-apoptotic Bcl2 in
liver tissue.
2-The administration of Moringa oleifera (MO) leaves
extract displayed a significant (P<0.05) reduction in the
enzyme activities of ALT, AST and GGT and caused a
significant increase in total protein. Also, displayed a
significant (P<0.05) reduction in GSSG, MDA and NO
level and increase in GSH when statistically compared
with VPA treated group throughout the experiment. MO
administration suppressed the elevation in the gene
expression of pro- apoptotic Bax and significant increase
in the anti-apoptotic gene bcl2.
3- Mepacure (MEPA) treatment to VPA induced a
gradual decrease in ALT, AST and GGT and a
significant increase in total protein levels. Meanwhile,
the results showed a significant reduction in TNF-α level
in a time dependent manner. Also, MEPA administration
showed a significant (P<0.05) improvement in oxidation
reaction parameters and reduction in the gene expression
of Bax and significant increase in the anti-apoptotic gene
bcl2.4- The co-administration of MO and MEPA exhibited a
significant attenuation in liver enzyme activities and
oxidative stress parameters also decline the elevation in
pro-apoptotic gene Bax and reduction in Bcl2 expression.
5- The results of this study have revealed that VPA has
caused different histopathological changes. The treated
liver with VPA showed a remarkable degeneration of
hepatocytes, aggregation of inflammatory cells
infiltration, congested blood vessels in a time dependent
manner. Meanwhile, administration of MO and/or MEPA
showing gradual enhancement in the histopathological
alternations include nil inflammation response and
congestion indicating reduction in hepatic damage
resulted from VPA administration through different
intervals.