Lipid-lowering, anti-inflammatory, and hepatoprotective effects of isorhamnetin on acetaminophen-induced hepatotoxicity in mice

Abstract

Isorhamnetin is a hepatoprotective flavonoid molecule derived from the leaves and fruits of <i>Hippophae rhamnoides</i> L. However, the protective effect of isorhamnetin on acetaminophen (APAP) induced hepatotoxicity is still unknown. Thus, we aimed to investigate the lipid-lowering, anti-inflammatory, and hepatoprotective effects of isorhamnetin on APAP-induced hepatotoxicity in mice. Hepatotoxicity was induced by a single injection of APAP (300 mg/kg, intraperitoneally). Isorhamnetin (50 or 100 mg/kg, orally) and N-acetylcysteine (NAC) (200 mg/kg, orally), or vehicle control, were administered 1 h before the administration of APAP. Total antioxidant status (TAS) and total oxidative status (TOS) of liver tissue and levels of inflammatory factors (TNF-α, IL-1β, and IL-6) were analyzed by ELISA. Lipid profiles and liver function parameters were measured using an autoanalyzer. In addition, liver tissue was examined histopathologically. Isorhamnetin treatment significantly reduced the APAP-induced increase in the liver weight and liver index; it also reduced the APAP-induced increase in serum liver parameters (ALT, AST, ALP, and LDH) (<i>p</i> < 0.05). Isorhamnetin significantly reduced APAP-induced oxidative stress and inflammation by increasing TAS levels and decreasing TOS, TNF-α, IL-1β, and IL-6 levels (<i>p</i> < 0.05). Moreover, isorhamnetin treatment significantly regulated lipid profiles (TG, T-C, LDL-C, and HDL-C levels) that changed in response to APAP administration (<i>p</i> < 0.05). In histopathological examination, liver degeneration observed in the APAP group was significantly reduced in the NAC and isorhamnetin-treated groups (<i>p</i> < 0.05). This study suggests that isorhamnetin has a significant protective effect on APAP-induced hepatotoxicity in mice through its lipid-lowering, antioxidant, and anti-inflammatory effects.