Hepatoprotective effect of silymarin-chitosan nanocomposite against aluminum-induced oxidative stress, inflammation, and apoptosis

Aluminum (Al) is abundant in the environment, and its toxicity is attributed to free radical formation and subsequent oxidative stress. While silymarin is a well-known antioxidant, its low water solubility and bioavailability limit its therapeutic effects. This study was designated to formulate silymarin chitosan nanoparticles (SM-CS-NPs) and evaluate its ameliorative effect against hepatotoxicity induced by aluminum chloride (AlCl₃). SM-CS-NPs were prepared by ionotropic gelation method and characterized using different techniques. Rats were distributed into six groups (n=7/group), control, silymarin (SM; 15 mg/kg B.W), silymarin-chitosan nanoparticles (SM-CS-NPs; 15 mg/kg), aluminum chloride (AlCl₃, 34 mg/kg), SM or SM-CS-NPs administrated orally one hour before the treatment with AlCl₃ for 30 days, respectively. Results showed that supplementation of SM-CS-NPs or SM solo improved the antioxidant state and reduced oxidative stress. On the other hand, the pretreatment with SM-CS-NPs or SM followed by AlCl₃ significantly restored liver functions (AST, ALT, ALP, LDH, total protein, albumin, globulin, and bilirubin) and modulated oxidative stress biomarkers (TBARS and H₂O₂), with improved cellular antioxidant defense (SOD, CAT, GPx, GR, GST, and GSH) and maintained normal liver histological structure compared to rats treated with AlCl₃ alone. Furthermore, they alleviated the inflammation and apoptosis by downregulating the expression level of COX-2, caspase-3, and TNFα. This ameliorative effect was stronger with silymarin nanoform than in bulk-state silymarin. According to the findings, silymarin preparation in nanoform boosts its ameliorative and protective effects against AlCl₃ hepatotoxicity.