Oxidative stress, inflammation and infertility in valproate treated rats

ABSTRACT

To investigate the effect of valproate monotherapy on total testosterone, dehydroepiandrosterone [DHEA], tumor necrosis factor alpha [TNF-alpha], oxidative stress markers, lipids and trace elements following acute, chronic and withdrawal of the drug in rats. Biochemistry Department, Faculty of Pharmacy, Zagazig University and Agricultural Research Center, Egypt. Four groups of male rats were used. The first one was kept on a standard-pellet rat diet [control group]. The other treated groups were either injected with valproate [50 mg/Rat, I.P] 2h prior to sampling [acute group], fed 20g valproate/kg diet for 2 weeks [chronic group] or fed valbproate for 2 weeks and then fed normal diet for 2 days [withdrawal group]. Serum testosterone and DHEA were evaluated by the electrochemiluminescence immunoassay. TNF-alpha was estimated by Enzyme Linked Immunosorbent Assay [ELISA]. Testicular lipid peroxides, hydroxyproline [HPR] and glutathione [GSH] were determined by colorimetry. Serum triacylglycerols [TG] and total cholesterol [TC] were estimated enzymatically using commercially available kits. Atomic absorption/flame Emission Spectrophotometry was used for evaluating trace elements [Cu[2+], Zn[2+], Se[2+]]. Histopathological assessment was done by light microscopy. Significant increase in serum levels of TNF-alpha and Se[2+], testicular lipid peroxides, and HPR were observed. Meanwhile, total testosterone, DHEA, TG and testicular GSH were significantly decreased. Non significant fluctuations were reported in the other tested parameters. Remarkable histopathological alterations were found in testicular tissues following acute and chronic supplementation of valproate. The present study has shown a drug-specific effect of valproate monotherapy on the tested parameters in non-epileptic male rats, indicating the comorbidity associated with valproate including altered levels of TNF-alpha, testosterone and testicular contents of lipid peroxides, GSH and HPR. Further studies are required to reveal the clinical implication of these findings: