Neonatal Orally Administered Zingerone Attenuates Alcohol-Induced Fatty Liver Disease in Experimental Rat Models

Abstract

Alcohol intake at different developmental stages can lead to the development of alcohol-induced fatty liver disease (AFLD). Zingerone (ZO) possess hepato-protective properties; thus, when administered neonatally, it could render protection against AFLD. This study aimed to evaluate the potential long-term protective effect of ZO against the development of AFLD. One hundred and twenty-three 10-day-old Sprague-Dawley rat pups (60 males; 63 females) were randomly assigned to four groups and orally administered the following treatment regimens daily during the pre-weaning period from postnatal day (PND) 12-21: group 1-nutritive milk (NM), group 2-NM +1 g/kg ethanol (Eth), group 3-NM + 40 mg/kg ZO, group 4-NM + Eth +ZO. From PND 46-100, each group from the neonatal stage was divided into two; subgroup I had tap water and subgroup II had ethanol solution as drinking fluid, respectively, for eight weeks. Mean daily ethanol intake, which ranged from 10 to 14.5 g/kg body mass/day, resulted in significant CYP2E1 elevation (p < 0.05). Both late single hit and double hit with alcohol increased liver fat content, caused hepatic macrosteatosis, dysregulated mRNA expression of SREBP1c and PPAR-α in male and female rats (p < 0.05). However, neonatal orally administered ZO protected against liver lipid accretion and SREBP1c upregulation in male rats only and attenuated the alcohol-induced hepatic PPAR-α downregulation and macrosteatosis in both sexes. This data suggests that neonatal orally administered zingerone can be a potential prophylactic agent against the development of AFLD.