Immunotoxicity of aristolochic acid I on early zebrafish (Danio rerio) embryos

Aristolochic acids (AAs) are active constituents of many traditional Chinese medicinal herbs. While AAs are known to induce cytotoxicity and pathological changes, such as tissue fibrosis, their specific impact on the immune system remains to be fully elucidated. This investigation used zebrafish as a model animal to evaluate the effects of aristolochic acid I (AAI), the main component of AAs, on the development and function of the early immune system. Our study found that exposure to AAI significantly decreased the numbers of macrophages, neutrophils, and T cells. Moreover, AAI exposure impaired the migratory capacity of immune cells to wound sites and weakened the immune system's response to external stimuli. Further research revealed that AAI exposure induced strong oxidative stress in zebrafish, activated the p53 signaling pathway, and subsequently induced apoptosis of immune cells. Fullerene, a potent antioxidant, is capable of inhibiting the p53 signaling pathway and rescuing the reduction of immune cells induced by AAI. Collectively, our findings indicated that AAI could induce immune cell death and impair immune function during early development via activation of the p53 signaling pathway, thereby uncovering the detrimental effects of AAs on the immune system and their underlying mechanisms. These findings provide a theoretical basis for the rational use of traditional Chinese medicinal herbs containing AAs.