Apocynum venetum L. leaf extract attenuates acetaminophen overdose-induced liver injury in mice

Apocynum venetum L. has long been used in oriental folk medicine to treat some liver diseases, the underlying mechanisms remain to be fully established. Acetaminphen (APAP) is a widely used analgesic drug that can lead to acute liver injury in overdose situation. In this study, we investigated the potential protective effects of A. venetum leaf extract (AVLE) on APAP-induced hepatotoxicity in mice. Male Kunming mice were intra-gastrically administered with AVLE (50, 100 and 150 mg/kg, respectively) once daily for three consecutive days prior to a single intra-peritoneal injection of APAP (300 mg/kg). APAP alone caused severe liver injury characterized by significantly increased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, hepatic malondialdehyde (MDA) and 3-nitrotyrosine (3-NT) formation, as well as liver superoxide dismutase (SOD), glutathione (GSH) and glutathione peroxidase (GPx) depletion. These liver damages induced by APAP were significantly attenuated by AVLE pretreatments. In addition, AVLE prevented APAP-induced apoptosis and necrosis, indicated by liver histopathological examination, immunohistochemical analysis and DNA laddering. Furthermore, according to the results from western blot analysis, AVLE decreased APAP-induced caspase-3, caspase-8 and cytochrome C expressions in mouse livers markedly. Together, these results suggest A. venetum possesses hepatoprotective effects which at least involve antioxidant action.

Keywords: Apocynum venetum, Acetaminophen, hepatotoxicity, oxidative stress, nitric oxide