Aristolochic Acid I-Induced Hepatotoxicity in Tianfu Broilers Is Associated with Oxidative-Stress-Mediated Apoptosis and Mitochondrial Damage

SIMPLE SUMMARY: Aristolochic acid (AA) is a component of traditional Chinese herbs and commonly used in the farm poultry industry in China for anti-infection, anti-viral and anti-bacterial treatment. However, long-term and over-exposure of these drugs has been proven to be associated with serious hepatotoxicity, but the mechanism of AA-I-induced hepatotoxicity remains unknown. Therefore, in this study, a subchronic toxicity test was conducted to evaluate the mechanism of AA-I-induced hepatotoxicity in Tianfu broilers. Subchronic exposure to high doses of AA-I in broilers can cause serious hepatotoxicity by breaking the redox balance to form oxidative stress, along with promoting oxidative-stress-mediated apoptosis and mitochondrial damage. In conclusion, AA-I has been found to damage broilers’ livers in high doses. This study provides suggestions for the clinical application of traditional Chinese medicine containing AA-I in the poultry industry. ABSTRACT: Aristolochic acid (AA) is a component of traditional Chinese herbs and commonly used for farm animals in China. Over-exposure of AA has been proven to be associated with hepatotoxicity; however, the mechanism of action of AA-I-induced hepatotoxicity remains unknown. In the current study, a subchronic toxicity test was conducted to evaluate the mechanism of AA-induced hepatotoxicity in Tianfu broilers. According to the results, AA-I-induced hepatotoxicity in Tianfu broilers was evidenced by the elevation of liver weight, levels of serum glutamic oxalacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT). Furthermore, hepatocyte swelling, vesicular degeneration and steatosis were observed. Additionally, AA-I elevated the production of reactive oxygen species (ROS) and induced oxidative stress, which further led to excessive apoptosis, characterized by mitochondrial depolarization, upregulation of Bax, and down-regulation of Bcl-2 expression. In conclusion, the mechanism of AA-I-induced hepatotoxicity was associated with oxidative-stress-mediated apoptosis and mitochondrial damage.