Hepatoprotective Activity of Ezetimibe Against Risperidone-Induced Liver Injury in Rats

Abstract

Abstract Background: Drug-induced hepatic injury is an unfavorable reaction to medications and/or their byproducts, which can result in ongoing harm to liver function and even death. Risperidone, the second most prescribed antipsychotic drug, has been linked to weight gain, abnormal hepatic enzyme levels, and further damage to liver cells. On the other hand, ezetimibe is an antihyperlipidemic agent that reduces serum cholesterol levels by inhibiting its absorption in the gastrointestinal tract. Additionally, it possesses antioxidant, hepatoprotective, and nephroprotective properties. Objectives: The purpose of this study is to evaluate the hepatoprotective and hypolipidemic effects of ezetimibe in mitigating liver damage induced by risperidone. Materials and Methods: A total of 24 adult male Swiss albino rats aged 6–7 weeks and weighing 170–180 g each were randomly divided into four groups, with 6 rats in each group. The first group served as a control and received vehicles only (0.5 mL of corn oil). Rats in the second group were administered risperidone alone at a dose of 2 mg/kg. In the last two groups, rats received a combination of risperidone (2 mg/kg) and ezetimibe at doses of 3 and 5 mg/kg, respectively. After sacrificing the rats, serum samples were collected to measure parameters related to lipid profile and liver enzymes. Additionally, liver tissue was immediately gathered for histopathological assessment using the NAS scoring system. Results: Ezetimibe exhibited marked hepatoprotective effects in rats exposed to risperidone-induced hepatic injury. This was achieved by significantly (P < 0.05) lowering adverse lipid profile components (TCHO, TG, LDL, and VLDL) and liver enzymes (ALT and AST), while at the same time significantly (P < 0.05) elevating the beneficial lipid profile (HDL). Moreover, Ezetimibe demonstrated remarkable liver protection by mitigating hepatic lobule destruction, inflammatory cell infiltration, and the presence of steatotic cells. Conclusion: Ezetimibe exhibited notable hepatoprotective and hypolipidemic properties in countering hepatic injury induced by risperidone.