الفهرس | Only 14 pages are availabe for public view |
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. |