Abd-Allah, HNasr, MAhmed-Farid, O.A.HIbrahim, B.M.MBakeer, R.MAhmed, R.F2020-10-242020-10-242020-12243205https://doi.org/10.1016/j.lfs.2020.118540https://t.ly/FVsgScopusAims: Non-alcoholic fatty liver disease (NAFLD) caused by consumption of high levels of fat and sugars (HFHS) in diet is considered one of the most dangerous medical complications among children and adolescents. Nicotinamide is among the promising candidates in ameliorating HFHS diet-induced NAFLD, but its use is limited by the possibility of prompting hepatotoxicity in high doses. Ascorbic acid is another promising candidate, however its use as a hepatoprotective agent is limited by its chemical instability. Therefore, the aim of the study was to overcome their delivery limitations and enhance their hepatoprotective activity by loading into nanoparticles. Key findings: In the present study, upon incorporating nicotinamide or ascorbic acid in chitosan nanoparticles, they ameliorated the insulin-resistant status induced in rats by a high-fat-high-fructose (HFHF) diet. Both formulae decreased serum level of ALT and AST, as well as liver tissue total cholesterol, triglycerides and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels. They also decreased oxidative and nitrosative stresses along with a significant increase in the hepatocellular energy. The biochemical findings were further confirmed by histopathological examination. Finally from the obtained data it could be concluded that chitosan nicotinamide nanoparticles at a dose level (10 mg/kg, p.o.) demonstrated beneficial pharmacological effect with safer toxicity profile than chitosan ascorbic acid nanoparticles. Significance: Nicotinamide chitosan nanoparticles could be recommended as daily supplement in the recovery from NAFLD. © 2020 Elsevier Inc.en-USAscorbic acidChitosanNanoparticlesNicotinamideNon-alcoholic fatty liver diseaseArticlehttps://doi.org/10.1016/j.lfs.2020.118540