Apigenin alleviated acetaminophen-induced hepatotoxicity in low protein-fed rats: Targeting oxidative stress, STAT3,...

Apigenin (API) is a natural flavonoid abundant in fruits and vegetables. The present study was undertaken to evaluate the effect of protein malnutrition (PMN) on acetaminophen (APAP)-induced hepatotoxicity, together with the protective effects of API, in male Wistar albino rats. In total, 64 male rats were divided into eight groups. Silymarin (SIL) (100 mg/kg, PO) as a reference standard and API (50 mg/kg, PO) were given to normal and APAP-induced hepatic injury in low protein-fed rats. The present results revealed that PMN significantly potentiated APAP-induced hepatotoxicity. Interestingly, the administration of SIL and API alleviated the induced damage, as revealed by reduced serum alanine aminotransferase and aspartate aminotransferase activities along with a significant improvement of the histopathological damage. API suppressed inflammatory response by reducing the interleukin-1β level and signal transducer and activator of transcription 3 expressions along with attenuating oxidative stress as shown by a significant reduction in liver contents of malondialdehyde and nitrite/nitrate as well as restoration of hepatic content of reduced glutathione and superoxide dismutase activity. API also counteracted apoptosis through downregulation of caspase-3 expression level. In conclusion, PMN greatly potentiated the hepatotoxic effects of APAP, and API produced a multimechanistic hepatoprotective activity that can be attributed to its antioxidant, anti-inflammatory, and antiapoptotic effects.