Abstract:
Mycotoxin contamination is a universal agricultural problem and a critical health issue. Fumonisin B1 (FB1) is a kind of the most toxic and extensive fumonisins that exists in various products and foods. Lycopene (LYC) as a natural carotenoid is becoming increasingly favored owing to its oxidation resistance. Mitophagy is a form of selective autophagy triggered by mitochondrial depolarization to remove damaged mitochondria. PANoptosis is a novel concept in the field of cell death, where pyroptosis, apoptosis, and necroptosis simultaneously occur. Here, we aim to explore the mechanism of FB1-induced hepatotoxicity and antagonism of LYC. How FB1 causes liver damage and the role of LYC in it have remained unclear. Here, we aim to explore the mechanism of FB1-induced hepatotoxicity and antagonism of LYC. In this study, we used chicken hepatocytes for in vitro experiments. Our findings indicated that LYC mitigated FB1-induced mitochondrial structure damage and loss of mitochondrial function, reducing apoptosis and oxidative injury in chicken hepatocyte. Furthermore, LYC reduced the expression of PANoptosis-related signal molecules that FB1-upregulated. LYC relieved FB1-induced reduction in SIRT1 and Ac-FOXO1 protein expression, which then facilitated mitophagy effects of engulfing and clearing damaged mitochondria. Most importantly, SIRT1 knockdown inhibited the protective effects of LYC in FB1-induced mitochondrial damage and PANopotisis. There, LYC alleviated FB1-induced chicken hepatocyte PANoptosis by regulating SIRT1-mediated mitophagy. Our study suggested that LYC targeted the SIRT1, alleviating FB1-induced mitophagy decline involving FOXO1-mediated mitophagy, which in turn inhibited the occurrence of PANoptosis in chicken hepatocytes. The findings showed the modulation of SIRT1, expounding the function of SIRT1-FOXO1 axis-mediated mitophagy in chicken hepatocyte injury. More importantly, this study presents a crucial insight into SIRT1 can serve as a target for regulating mycotoxins-induced chicken hepatocyte impairment.
