Protective Effects And Mechanisms Of Hesperidin Against Acute Chemical Liver Injuries In Mice

Currently antioxidant drugs a lot , but hesperidin of oxidative stress there is no reported. Abroad in recent years have HDN against acute liver injury research, but mainly to its serum, organizations reported, its pathology, few reports of molecular mechanisms, not the system. The issue of carbon tetrachloride were used, D-galactosamine induced acute liver injury in mice to study the HDN of acute chemical liver injury in mice with certain cytokines, inflammatory mediators such as the impact of the hesperidin on experimental liver injury as well as its possible mechanisms. The main results were as follows:1. Protective effects of HDN on CCl4-induced chemical liver injury mice and its partly mechanisms.Liver histopathological examination shows HDN(250,500 mg/kg)could ameliorate liver scope and extent of lesion to the model group. At the same time , HDN (500 mg/kg)ig could reduce the levels of ALT,AST obviously; HDN(250, 500 mg/kg)ig could increase the levels of SOD and GSH-PX. However the activity of MDA and NO were reduced only by HDN(500 mg/kg). All of these suggested that HDN had protective effects on CCl4-induced chemical liver injury. It was possibly related to remove free radicals and inhibit lipid peroxidation.Compared with model group, HDN(250,500 mg/kg)ig could reduce the levels of IL-1βin serum as well as inhibiting the mRNA expression of IL-1βin liver tissues. But only HDN(500 mg/kg)ig could reduce the levels of TNF-αin serum and liver tissues. All of these suggested that HDN had protective effects on CCl4-induced chemical liver injury. It was possibly related to inhibition of TNF-αand IL-1βlevels.2. Protective effects of HDN on D-GalN-induced chemical liver injury mice and its partly mechanisms.Liver histopathological examination shows HDN(250,500 mg/kg)could ameliorate liver scope and extent of lesion, alleviate inflammatory cell infiltrationin. Compared with normal group, ALT, AST levels of model group were significantly higher; Compared with model group, HDN (250,500 mg/kg)Could reduce the elevated AST level, but only the discrepancy of HDN (500 mg/kg)group had statistical significance to the elevated ALT level.Compared with normal group, MDA level of model group were significantly higher, meanwhile the activity of SOD, GSH-PX were reduced, HDN(250,500 mg/kg)could reduce the levels of MDA and NO as well as enhancing the activity of SOD, GSH-PX.Radioimmunoassay results of TNF-α,IL-1βin serum suggest that TNF-α,IL-1βlevels of model group were significantly higher, after administration of HDN(250, 500 mg/kg), the expression decreased with the dose increasing gradually. Meanwhile the mRNA expression of IL-1βwere inhibited in liver tissues by HDN(125,250,500 mg/kg), but only HDN(500 mg/kg)could inhibite the mRNA expression of TNF-αin liver tissues. HDN has the protective effect on D-GalN-induced acute chemical liver lesion in mice, and its mechanism might be related with decreasing the levels of TNF-α,IL-1βin serum, inhibiting the expression level of TNF-α,IL-1βmRNA and its anti-lipid peroxidation effect.