Neonatal Oral Administration of Chrysin Prevents Long-Term Development of Non-Alcoholic Fatty Liver Disease in a Sexually Dimorphic Manner in Fructose Nurtured Sprague Dawley Rats

High-fructose diets are linked with the development of non-alcoholic fatty liver disease (NAFLD), the management of which is a burden to society. Interventions with phytochemicals in the early postnatal period may prevent fructose-induced NAFLD later in adulthood. We investigated the protective potential of chrysin against fructose-induced NAFLD. Four-day-old male and female suckling Sprague Dawley rats (N = 112) were randomly grouped and orally gavaged daily with distilled water (negative Control-Cn + W), chrysin(Chr-100 mg/kg), fructose-solution (Fr-20% w/v), and Chr + Fr between postnatal day (PND) 4 and 21 and then weaned onto normal rat chow and plain drinking water to PND 55. From PND 56 to 130, half of the rats continued on plain water, and the rest had Fr as drinking fluid. Terminally, the liver tissue was collected, and the lipid content was determined and histologically assessed for NAFLD. Dietary Fr induced an increased hepatic lipid content (p = 0.0001 vs. Cn + W) both sexes, and it was only attenuated by neonatal Chr in female rats (p < 0.05). Histologically, there was increased microvesicular steatosis (p = 0.0001 vs. Cn + W) in both sexes, and it was prevented by neonatal Chr (p > 0.05). Fr caused macrovesicular steatosis (p = 0.01 vs. Cn + W) in females only, and chrysin did not prevent it (p > 0.05). Fr induced hepatocellular hypertrophy, and inflammation was observed in females only (p = 0.01 vs. Cn + W), and this was prevented by Chr (p > 0.05). The collagen area fraction was increased by Fr (p = 0.02 (males) and p = 0.04 (females) vs. Cn + W, respectively; however, chrysin did not prevent this (p > 0.05). Neonatal chrysin prevented some of the deleterious effects of the high-fructose diet on the liver, suggesting that chrysin should be further explored as a strategic prophylactic neonatal intervention against high-fructose-diet-induced NAFLD.