Hesperidin mitigates deoxynivalenol-induced renal ferroptosis and necroptosis by regulating VDAC3.
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Key Findings
Abstract
BACKGROUND: Deoxynivalenol (DON), a secondary metabolite widespread in cereals and feeds generated by fungi, poses a major threat to the global economy and food safety. DON constituted a serious risk to the health of agricultural animals through biological chain enrichment. Hesperidin (HDN) is renowned for its broad spectrum of sources and exceptional antioxidant capability. Despite the fact that numerous pharmacological activities of HDN have been understood, the underlying ameliorative mechanisms of HDN in reducing kidney damage caused by DON exposure remain unclear. PURPOSE: This study aimed to investigate mechanism of HDN against DON-induced nephrotoxicity. METHODS: We initially established an in vitro DON exposure model and administered two doses of HDN to TCMK-1. Proteomics, TEM, fluorescent probes, AFM, CETSA, and other techniques were employed to investigate whether HDN could mitigate DON-induced nephrotoxicity and specific mechanisms. Subsequently, in vivo validation was performed using C57BL/6 mice. RESULTS: We found that HDN could mitigate DON-induced TCMK-1 ferroptosis and necroptosis. Mechanistically, by targeting voltage-dependent anion channel 3 (VDAC3), HDN restored mitochondrial integrity and lowered mtROS buildup on TCMK-1 brought on by DON. In addition, DON-induced renal injury in mice was alleviated after HDN dosing intervention. CONCLUSIONS: HDN, a VDAC3 target-like chemical, might reduce the vulnerability of the kidney to ferroptosis and necroptosis brought on by DON exposure. Our study offers an innovative therapeutic approach with regard to DON-induced kidney damage.
Affiliation
Xintong Zhou
External References
- PubMed ID:
- 41038147
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