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 Hippophae
rhamnoides 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 100mg/kg,
orally) and N-acetylcysteine (NAC) (200mg/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-a, IL-1b, 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) (p<0.05). Isorhamnetin significantly reduced APAP-induced oxidative stress and inflammation
by increasing TAS levels and decreasing TOS, TNF-a, IL-1b, and IL-6 levels (p<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 (p<0.05). In histopathological examination, liver degeneration
observed in the APAP group was significantly reduced in the NAC and isorhamnetin-treated
groups (p<0.05). This study suggests that isorhamnetin has a significant protective effect on APAPinduced
hepatotoxicity in mice through its lipid-lowering, antioxidant, and anti-inflammatory effects.
Source
Drug and Chemical ToxicologyVolume
46Issue
3URI
https://www.tandfonline.com/doi/full/10.1080/01480545.2022.2069256https://hdl.handle.net/20.500.12418/14296