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 (AlCl). 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 (AlCl, 34 mg/kg), SM or SM-CS-NPs administrated orally one hour before the treatment with AlCl 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 AlCl significantly restored liver functions (AST, ALT, ALP, LDH, total protein, albumin, globulin, and bilirubin) and modulated oxidative stress biomarkers (TBARS and HO), with improved cellular antioxidant defense (SOD, CAT, GPx, GR, GST, and GSH) and maintained normal liver histological structure compared to rats treated with AlCl 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 AlCl hepatotoxicity.