Deoxynivalenol-mediated kidney injury via endoplasmic reticulum stress in mice.

OBJECTIVE

Deoxynivalenol (DON) is a common fungal toxin that poses significant health risks to humans and animals. The present study aimed to investigate the adverse effects and molecular mechanisms of DON-induced kidney injury.

METHODS

Male C57BL/6 mice aged 5-6 weeks were used to establish a DON-induced acute kidney injury model. Histological analysis, biochemical assays, molecular techniques, Western blot, RNA sequencing, and transmission electron microscopy were employed to analyze kidney damage, inflammation, oxidative stress, apoptosis, and endoplasmic reticulum (ER) stress.

RESULTS

DON disrupted kidney morphology, induced inflammatory cell infiltration, and triggered inflammatory responses. DON increased MDA content while decreasing antioxidant enzyme activity (SOD and CAT). It also triggered apoptosis, evidenced by elevated levels of caspase-12, cleaved caspase-3, and BAX, and reduced levels of Bcl-2. Transcriptomic analysis identified distinct expression patterns in 1756 genes in DON-exposed mouse kidneys, notably upregulating ER stress-related genes. Further investigation revealed ultrastructural changes in the ER and mitochondrial damage induced by DON, along with increased levels of p-IRE1, p-PERK, and their downstream targets, indicating unfolded protein response (UPR) activation in the kidney. The ER stress inhibitor 4-Phenylbutyric acid (4-PBA) significantly mitigated DON-induced ER stress, oxidative damage, apoptosis, tissue injury, ER expansion, and mitochondrial damage.

CONCLUSION

Our findings highlight the role of ER stress in DON-induced kidney injury and the protective effect of 4-PBA against these adverse effects.