Hepatoprotective effect of Swertiamarin from Cytarabine Induced Hepatotoxicity in Pregnant rats

Abstract

Cytarabine (Ara-C) is a nucleoside analogue that is used to treat cancer as well as viral infections. It is hepatotoxic and induces oxidative stress. Swertiamarin (ST) is a natural antioxidant that protects the liver from hepatotoxicity caused by medication or toxicant exposure or pathological conditions. The purpose of this investigation was to see if ST could protect pregnant rats against Ara-C-induced hepatotoxicity. Pregnant rats were separated into six groups and given normal saline, Ara-C 25mg/kg, ST 100mg/kg, ST 200mg/kg, Ara-C 25mg/kg plus ST100 mg/kg, and Ara-C25mg/kg plus ST200 mg/kg from gestation day (GD8 to GD20) before being euthanized on GD21. Ara-C treatment resulted in a significant and dose-dependent decrease in weight gain, increased oxidative stress in pregnant rats by increasing MDA levels (p<0.01) and decreasing CAT (p<0.01), GSH (p<0.01), GSH-Px (p<0.01), and SOD (p<0.01) levels, and an increase in enzyme markers AST (p<0.01), ALT (p<0.01), urea (p˂0.01) and creatinine levels (p˂0.01). Furthermore, significant vacuolization, poor tissue architecture, and the formation of pycnotic nuclei and dilated sinusoids were identified in the livers of Ara-C treated rats verses control rats. These data suggest that ST supplementation protects rats from hepatotoxicity caused by Ara-C prenatal exposure. Future research should look into the mechanisms involved in ST's protective impact against Ara-C-induced hepatotoxicity.