The long-term protective effects of neonatal administration of curcumin against nonalcoholic steatohepatitis in high-fructose-fed adolescent rats.

There is an increased prevalence of nonalcoholic steatohepatitis (NASH) in adolescents. The suckling period is developmentally plastic, affecting later health outcomes. We investigated whether neonatal administration of curcumin would provide protection against the development of NASH later in adolescence in rats fed a high-fructose diet. From postnatal day (PN) 6 to PN 21, the pups (N = 128) were allocated to four groups and orally gavaged daily with either 0.5% dimethyl sulfoxide solution (vehicle control), curcumin (500 mg·kg-1 ), fructose (20%, w/v) or curcumin and fructose combined. All the pups were weaned and half the rats in each group had tap water, whereas the other received fructose (20%) as their drinking fluid ad libitum for 6 weeks. The rats' liver NASH scores, lipid content, and RNA gene expression ratios of AMPKα and TNFα were determined. Hepatic lipid content was similar across the treatment groups in the males (P > 0.05, ANOVA). In the females, the hepatic lipid content in the treatment groups ranged from 2.7 to 4.3%. The livers of male and female rats that had fructose either as neonates and/or postweaning had significantly marked inflammation (P = 0.0112, Kruskal-Wallis) and fibrosis (P < 0.0001, ANOVA) which were attenuated by curcumin. The hepatic gene expression ratios for AMPKα in both sexes were significantly downregulated (P < 0.0001, ANOVA), whereas the expression ratios of TNFα were significantly upregulated (P < 0.0001) in rats fed a high-fructose diet pre and/or postweaning compared to the other groups. Neonatal curcumin administration is a potential natural pharmacological candidate for the prevention of NASH.