Honokiol antagonizes cadmium-induced ultrastructural nuclear variation and mitochondrial dysfunction of hepatocytes through targeting Bax protein

Cadmium (Cd) induces oxidative stress and inflammation, leading to hepatotoxicity in animals. Honokiol (HNK) has gained much attention owing to its anti-inflammatory and antioxidant properties, and may offer protection against liver diseases. However, whether HNK can improve Cd-induced ultrastructural and functional variation in hepatocytes is largely unknown. In this study, day-old broiler were divided into four treatment groups including control/untreated group Cd (50mg/L), HNK (50mg/kg), and Cd+HNK (50mg/L+50mg/kg) for 42 days, respectively. In Silico analysis was conducted to reveal the potential interaction of HNK with Bax and Bcl-2 proteins to determine how HNK affected these two protein targets to mediate the effects of Cd toxicity. Results revealed that Cd exposure caused significant damage to the ultrastructure and functional activity of hepatocytes compared to the control group. Notably, HNK treatment helped recover and maintain the integrity of the nucleus and mitochondrial cristae in hepatocytes. In addition, HNK reduced oxidative stress with the increased activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and decreased malondialdehyde (MDA) content in the liver tissue. The HNK prevented lipid accumulation in the liver tissue induced by cadmium toxicity. Furthermore, HNK decreased the expression of apoptotic protein and gene expression of Caspase-3, and increased expression of the anti-apoptotic protein Bcl-2 by immunohistochemistry and qPCR. In conclusion, findings of the present study revealed the potential of HNK to alleviate Cd-induced ultrastructural and functional perturbations that cause hepatotoxicity in chicken, making it a promising therapeutic agent for Cd poisoning in animals.