Valproic acid (VPA) is a widely-used antiepileptic drug that has been extensively reported to cause hepatotoxicity. Monomethyl fumarate (MMF) is a compound that has been reported to produce hepatoprotective and antioxidant effects. This study was aimed at studying the alleviative effects of MMF on VPA-induced hepatotoxicity in rats. The test animals were divided into nine groups, each of six rats, as different cases and one group as control. VPA was intraperitoneally administered (500 mg/kg) once daily for 7 days. The VPA-exposed rats were then treated with two doses (25 and 50 mg/kg) of MMF and silymarin. Biochemical parameters and oxidative stress markers as well as histopathological examination were employed to evaluate the effect of these compounds on VPAhepatotoxicity. VPAadministration caused hepatotoxicity in rats as evidenced by significant increase in the levels of aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), liver malondialdehyde (MDA), and significant reduction in glutathione (GSH) content compared to values in the control group. The administration of MMF or silymarin attenuated VPA-induced oxidative hepatotoxicity as evidenced by significant decrease in serum liver function tests together with marked improvement in oxidative stress markers. Thus, the treatment with MMF and/or silymarin improved histopathological patterns of liver tissue to a considerable degree. MMF treatment can exert protective effects (similar to those of silymarin) against VPA-induced hepatotoxicity. This amelioration can result from a considerable reduction of the oxidative stress. Moreover, a combination therapy was more effective than MMF or silymarin monotherapy alone. A dose of 25 mg/kg was as effective as 50 mg/kg for either MMF or silymarin.

丙戊酸 (VPA) 是一种广泛使用的抗癫痫药物，已被广泛报道会引起肝毒性。富马酸单甲酯 (MMF) 是一种据报道具有保肝和抗氧化作用的化合物。本研究旨在研究 MMF 对 VPA 诱导的大鼠肝毒性的缓解作用。试验动物分为九组，每组六只，作为不同的病例，一组作为对照。VPA 腹膜内给药 (500 mg/kg) 每天一次，共 7 天。然后用两种剂量（25 和 50 毫克/千克）的 MMF 和水飞蓟素治疗暴露于 VPA 的大鼠。生化参数和氧化应激标志物以及组织病理学检查被用来评估这些化合物对 VPA 肝毒性的影响。VPA 给药导致大鼠肝毒性，如转氨酶 (AST)、丙氨酸转氨酶 (ALT)、碱性磷酸酶 (ALP)、乳酸脱氢酶 (LDH)、肝脏丙二醛 (MDA) 水平显着增加和谷胱甘肽 (GSH) 显着降低所证明) 内容与对照组中的值进行比较。MMF 或水飞蓟素的给药减弱了 VPA 诱导的氧化性肝毒性，这可以通过血清肝功能测试的显着降低以及氧化应激标志物的显着改善来证明。因此，用 MMF 和/或水飞蓟素治疗在相当程度上改善了肝组织的组织病理学模式。MMF 治疗可以对 VPA 诱导的肝毒性发挥保护作用（类似于水飞蓟素）。这种改善可能是由于氧化应激的显着减少。此外，联合疗法比单独使用 MMF 或水飞蓟素更有效。对于 MMF 或水飞蓟素，25 毫克/千克的剂量与 50 毫克/千克的剂量一样有效。