The Ameliorative Effect of Monomethyl Fumarate and Silymarin Against Valproic Acid Induced Hepatotoxicity in Rats Publisher



Keshavarzmaleki R^{1, 2} ; Shalmani AA^{1, 2} ; Gholami M¹ ; Sabzevari S^{1, 2} ; Rahimzadegan M^{1, 2} ; Jeivad F^{1, 2} ; Sabzevari O^{1, 2} Show Affiliations
Source: Pharmaceutical Chemistry Journal Published:2021

Abstract

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. © 2021, Springer Science+Business Media, LLC, part of Springer Nature.