SeMet attenuates zearalenone-induced autophagy in rabbit kidney to alleviate apoptosis through activation of PI3K/Akt/mTOR signaling pathway

Zearalenone (ZEA), a prevalent mycotoxin in moldy feeds, induces apoptosis by disrupting cellular homeostasis, leading to multi-organ damage, particularly in the kidneys, intestines, and reproductive system. Selenomethionine (SeMet), a natural amino acid with antioxidant and anticancer properties, was investigated for its protective effects against ZEA-induced nephrotoxicity. In this study, rabbits were exposed to ZEA and varying concentrations of SeMet, followed by renal tissue analysis. Pathological examination revealed significant structural damage in ZEA-treated kidneys, including glomerular atrophy, fibrosis, impaired glycogenolysis, and inflammatory injury due to dysregulated pro-inflammatory and anti-inflammatory factor expression. Mechanistically, ZEA suppressed PI3K/Akt/mTOR signaling, triggering excessive autophagy initiation but impairing autophagic flux, ultimately disrupting cellular homeostasis. This dysregulation upregulated pro-apoptotic proteins (Cyt C, Caspase-3, Caspase-9) while downregulating Bcl-2, exacerbating renal apoptosis. SeMet supplementation counteracted these effects by restoring PI3K/Akt/mTOR pathway activity, normalizing autophagy, and rebalancing apoptotic protein expression. Notably, 0.35 mg/kg SeMet demonstrated optimal renal protection. These findings highlight SeMet's potential as a dietary supplement to mitigate ZEA-induced kidney injury via modulation of autophagy and apoptosis pathways.