Hesperidin mitigated deoxynivalenol-induced liver injury by inhibiting ROS/ P53/ PGC-1α-mediated disruption of mitochondrial dynamics and PANoptosis.

BACKGROUND

Deoxynivalenol (DON) is a physico-chemically stable food contaminant that is difficult to destroy during food production and culinary processing. Consumption of food contaminated with DON can impair the liver's antioxidant capacity and trigger various forms of programmed cell death. Hesperidin (HDN) is a highly antioxidant flavonoid compound with excellent biological activity and is a potential drug for treating liver damage. While the various pharmacological actions of HDN have been increasingly clarified over time, its protective role and precise mechanisms in mitigating liver damage caused by DON exposure are still largely shrouded in mystery.

PURPOSE AND

METHODS

To investigate the potential of HDN to mitigate DON-induced liver injury and elucidate its specific mechanisms of action, we established both in vitro and in vivo models of DON exposure and administered HDN intervention.

RESULTS

Our findings revealed that DON exposure triggered oxidative stress in the liver, DNA damage, and P53 pathway activation, resulted in mitochondrial dynamics disorder and dysfunction, and induced PANoptosis in the liver. HDN significantly attenuated these changes. Using COIP, protein-protein molecular docking, and immunofluorescence methods, we discovered that PGC-1α and P53 can connect tightly, regulating the dynamics and function of the mitochondria. In addition, we intervened in vitro using the N-acetyl-l-cysteine, the pifithrin α, and the Mito TEMPO.

CONCLUSION

The findings demonstrated that HDN attenuated PANoptosis induced through mtROS overproduction by inhibiting ROS/ P53/ PGC-1α-mediated mitochondrial damage, which ameliorated DON-induced liver injury.