Inositol-6-phosphate mitigates deoxynivalenol nephrotoxicity in pig kidney explants

Abstract

Abstract Deoxynivalenol (DON) is a mycotoxin that frequently contaminates food crops and negatively impacts human and animal health. While inositol-6-phosphate (IP6) is known to counteract DON-induced intestinal damage, inflammation, and oxidative stress, its ability to alleviate DON-caused kidney injury is yet unexplored. This study assessed DON’s kidney effects and IP6’s protective capability using an ex vivo renal explants model. From 360 explants taken from six pigs, four groups were formed: control (culture medium), DON (10 μM equivalent to 3 mg/kg of feed), IP6 group (5 mM), and DON + IP6 (10 μM + 5 mM). DON elevated creatinine levels and γ-glutamyl transferase activity in the culture medium. It led to cytoplasmic vacuolation in convoluted tubular epithelial cells and tubular necrosis, a drop in antioxidant potential (ABTS) and a rise in interleukin (IL)-8 mRNA. The introduction of IP6 restored renal histological and functional parameters, bolstered antioxidant status, enhanced IL-10 gene expression, and reduced superoxide anion levels. These results indicate that within the model of renal explants, IP6 significantly alleviates the nephrotoxic effects of DON while efficiently regulating the antioxidative and anti-inflammatory response within the kidneys.