Insights into the Therapeutic Potential of Silymarin-encapsulated CME@ZIF-8 Against CCl4-induced Toxicity in Broiler Chicks

Carbon tetrachloride (CCl 4 ) damages several organs by inducing oxidative stress. Silymarin exhibits strong antioxidant properties; however, its therapeutic potential is limited due to its low bioavailability. This study examined the protective efficacy of silymarin-encapsulated Cordia myxa extract-based ZIF-8 nanocomposites (CME@ZIF-8) against CCl 4 -induced toxicity in the brain, spleen, and intestine of broiler chicks. Following toxicity induction with CCl 4 , broiler chicks were treated with CME@ZIF-8 nanocomposites loaded with silymarin (Sil@CME@ZIF-8). Absolute and relative weights of selected visceral organs, oxidative stress biomarkers (TBARS and ROS), antioxidant enzyme activities (CAT, POD, and SOD), histopathological changes, and genotoxicity, assessed using the comet assay, were evaluated in chickens. Results revealed significantly increased absolute and relative weight of visceral organs, higher values of oxidative stress biomarkers, antioxidant enzyme depletion, and severe microscopic alterations in the brain (neuronal necrosis), spleen (depletion of lymphoid tissue) and in intestine (necrosis of enterocytes and epithelium of villi) in CCl 4 -treated chickens. The results on genotoxicity determined using the comet assay exhibited extensive fragmentation of DNA in the isolated cells of visceral organs of CCl 4 -treated chickens. The administration of Sil@CME@ZIF-8 (5, 10, and 15 mg/kg body weight) remarkably mitigated toxic/adverse effects in a dose-dependent manner by restoring organ weight, normalizing antioxidant defense system, improving oxidative biomarkers, reducing severity of histopathological abnormalities in visceral organs and DNA damage. Sil@CME@ZIF-8 nanocomposites displayed substantial therapeutic potential against CCl 4 -induced multi-organ toxicity in broiler chicks. The nano-formulation enhanced the bioavailability and therapeutic potential of silymarin suggesting that it can be used in veterinary medicine and as a protective agent against chemical-induced toxicity in poultry.