Hepatoprotective Efficacy of Silymarin-loaded Metal-Organic Frameworks Against CCl4 Toxicity in Broilers: A Dose-dependent Study

Carbon tetrachloride (CCl 4 ) induced hepatotoxicity remains a significant concern in poultry production, and its remedial strategies are urgently needed. The present study investigated the silymarin-loaded metal-organic frameworks (MOFs) as a new nano-delivery system to treat liver damage instigated by CCl 4 in broiler chickens. A total of 105 broilers were randomly placed in seven groups (n=15 each): control group (A), CCl 4 -treated group (B), CCl 4 +conventional silymarin group (C), MOF-only group to evaluate biocompatibility (D), and three CCl 4 -intoxicated groups (E, F, and G) treated with different concentrations of Silymarin@ZIF-8 (5, 10, and 15 mg/kg), respectively. Hepatotoxicity was induced using CCl 4, followed by a 20-day treatment period. The different tissues from each experimental bird were collected and evaluated on days 10 and 20 of the trial. Comprehensive assessments included changes in body weight, relative weight of liver, hematological indices, liver function tests, oxidative and antioxidant biomarkers, histopathological analysis of hepatic tissues, and DNA damage analysis through the comet assay. Results revealed that CCl 4 exposure induced substantial hepatic dysfunctions as manifested by the altered hematological parameters, elevated contents of liver function tests, pronounced histological ailments and increased percentile rate of DNA damage. Treatment with silymarin@ZIF-8 1(0 and 15 mg/kg) conferred dose-dependent hepatoprotection and superior therapeutic efficacy compared with conventional silymarin administration. The nano-formulation effectively restored the levels of liver enzymes, histoarchitecture, minimized oxidative DNA damage, and normalized hematological profiles. Comet assay results showed a significant attenuation of DNA damage, indicating effective protection against CCl4-induced oxidative stress. The MOF carriers showed high biocompatibility, with no undesirable effects observed in the MOF-only birds. Among the tested doses, silymarin at 15 mg/kg produced the most pronounced hepatoprotective effects, which can be attributed to a higher bioavailability and specific delivery of the active ingredient. These results suggest that silymarin@ZIF-8 represents a promising therapeutic approach for chemical-induced hepatotoxicity in poultry, offering improved efficacy than silymarin traditional formulations due to better drug delivery and bioavailability.