Zeaxanthin Dipalmitate Alleviates Hepatic Injury Induced By Superimposed Chronic Hepatitis B And Non-alcoholic Steatohepatitis In Non-obese Mice

Aim: To investigate the protective effects and potential mechanisms of ZD in a non-obese mouse model with superimposed chronic hepatitis B(CHB)and non-alcoholic steatohepatitis(NASH).Methods: The hepatitis B virus(HBV)transgenic mice were used to establish the superimposed model of CHB and NASH by feeding the methionine choline-deficient diet(MCD)for 8 weeks,with or without 2 mg/kg zeaxanthin dipalmitate(ZD)for 3 times per week.Biochemical,histological and molecular parameters of mice were measured at the end of week 8.Results: Both wild-type and HBV transgenic mice gained typical non-obese NASH phenotypes,including body weight reduction,abnormal biochemical indexes,hepatic fat droplet accumulation,inflammatory cells infiltration,moderate fibrosis,oxidative stress,inflammation,and apoptosis,with 8-week MCD diet feeding.ZD developed evident therapeutic effects through the alleviation of those pathological events and the recovery of liver functions.When compared with the HBV transgenic mice,superimposed NASH significantly increased HBV viral replication and serum antigen expression,and those parameters were also reduced by the ZD administration.Moreover,long-term(90-day)vehicle-ZD treatment did not induce any detectable adverse effect on healthy mice.Conclusion: ZD is a promising and safe hepato-protective agent against superimposed CHB and NASH-induced liver injury.