Abstract
Alcohol intake at different developmental stages can lead to the development of alcoholinduced
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), group2—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-a 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-a 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.