Melatonin protects against GalN/LPS-induced acute liver injury in mice

Aim To investigate the effects of Melatonin(MT) on GalN/LPS-induced acute liver injury in mice.Methods A model of apoptotic liver injury was induced by injection of D-galactosamine(GalN) in mice given together with a low sublethal dose of lipopolysaccharide(LPS).Female CD-1 mice were treated with MT(5.0 mg·kg-1,ip) at 30 min before and MT(2.5 mg·kg-1,ip) at 1 h,2 h after GalN/LPS.Mice were sacrificed at 8 h after GalN/LPS.Blood serum was collected for measurement of alanine aminotransferase(ALT),TNF-α,and nitrate plus nitrite.Livers were dissected for measurements of Caspase-3 activity,GSH content,GSH-PX activity,GSH-RD activity,histological change,and DNA laddering.Results Treatments with MT significantly attenuated GalN/LPS-induced increase in serum ALT activity and TNF-α concentration,alleviated hepatic caspase-3 activity,GSH depletion,and DNA laddering,increased GSH-PX and GSH-RD activity,and improved liver histological change in mice.However,MT had no effect on GalN/LPS-induced serum nitric oxide(NO) production.Conclusions MT attenuates GalN/LPS-induced acute liver injury via its anti-inflammatory,antioxidant,and anti-apoptotic effects.