الفهرس 
IntroductionOnly 14 pages are availabe for public view
 |  | from | 162 |  |  |
| | | from | 162 | | |
Abstract
In this study the role of erythropoietin in prevention of Valproic acid undesirable adverse effects focusing on hepatotoxicity was studied. We also evaluated the mechanisms by which Valproic acid induced these side effects and how Erythropoietin prevented them. We focused on the antioxidant, anti-inflammatory and anti-apoptotic properties of erythropoietin in prevention of side effects.
Materials & Methods:
Intervention was performed in one month. We experimented on 40 adult male Wistar Albino rats. Animals were randomly allocated into 3 groups each one contains 10 rats and they were housed four rats per cage.
• group 1 (Control group): It was regarded as normal animals and kept under the same laboratory conditions After induction of hepatotoxicity 30 rats are then subdivided into four equal groups as following:
• group 2 (Valproic group):
Rats were given the Valproic acid dose of 500mg/kg intraperitoneally every day for 2 weeks and were kept under the same laboratory conditions. (Khodayar et al.,2021).
• group 3 (prophylactic group):
In addition to Valproic acid 500mg/kg every day for 2 weeks (Khodayar et al.,2021). the rats were injected at the same time intraperitoneally with recombinant erythropoietin 2000IU/kg every other day for 2 weeks (Said et al., 2022).
• group 4 (treatment groups):
Rats were injected with 500mg/kg Valproic acid intraperitoneally for 2 weeks (Khodayar et al.,2021) and then were injected with 2000IU/kg EPO every other day for another 2 weeks (Said et al.,2022).
In order to study the beneficial effects of erythropoietin on prevention of Valproic acid induced side effects, we assessed liver functions by evaluation of ALP, AST and ALT and RBCs count. For oxidative stress, SOD, MDA ,HIF-1 alpha and HO-1 were measured. For Inflammation assessment, IL-1B was measured. We also measured markers for apoptosis including gene expression of SIRT1, P53 and Cytochrome C, also for assessment of fibrosis TGF- B was measured and histopathological examination of liver was performed.
Results:
Serum levels of ALT, AST and ALP, levels of MDA, IL-1B hepatic gene expression of HIF-1,P53,Cytochrome C, and TGF-B significantly increased after Valproic acid injection in all rats .Also the hepatic gene expression of SIRT1 and hepatic level of SOD and HO-1 significantly decreased in all rats denoting liver affection and hepatotoxicity.
Whereas after EPO these results show significant improvement in liver functions as Serum levels of ALT, AST and ALP, levels of MDA, IL-1B hepatic gene expression of HIF-1,P53,Cytochrome C, and TGF-B significantly decreased almost to normal level in group 3 more than group 4 and hepatic gene expression of SIRT1 and hepatic level of SOD and HO-1 significantly increased to almost normal levels in group 3 better than group.