Dietary genistein alleviates arsenic trioxide-induced ionoregulatory disruption, oxidative and endoplasmic reticulum stress, and apoptotic gene expression in the gills and kidneys of Oreochromis niloticus.

Arsenic trioxide (ATO) is a widespread aquatic pollutant known to induce oxidative stress and impair physiological functions in fish. This study examined the protective role of dietary genistein (GN, 500 mg/kg diet), a natural isoflavone, against waterborne ATO (10 µg/L)-induced gills and kidneys toxicity in Oreochromis niloticus through biochemical, molecular, and histopathological assessments over 60 days. ATO exposure significantly impaired antioxidant gills and kidneys defense mechanisms, reduced Ca²⁺-ATPase and Na⁺/K⁺-ATPase activities, disrupted ion homeostasis, elevated serum levels of uric acid, creatinine, urea, cortisol, and glucose, and increased As accumulation in the gill tissues. Additionally, ATO markedly downregulated ion transport gene expression (atp6v1ab, slc4a4a, and nka-α3) in gill tissues and upregulated apoptotic and endoplasmic reticulum (ER) stress markers (casp3, chop, jnk, and xbp1). Similarly, antioxidant-related genes (gpx, cat, and sod) were downregulated in the posterior kidney, while hsp70 and hsp90 were significantly induced. Dietary GN significantly ameliorated ATO-induced alterations, partially restoring antioxidant enzyme activities, enhancing antioxidant gene expression, attenuating stress markers, and reducing tissue As levels. Notably, GN attenuated the ATO-induced alteration in the ion homeostasis and the expression of ion transport and ER stress-related genes. Moreover, GN induced partial protection in gills but provoked more pronounced improvements in kidney architecture, reflecting tissue-specific responses. These findings revealed the protective effects of GN against ATO-induced toxicity in O. niloticus, highlighting its prospective as a dietary supplement in aquaculture to mitigate metal-induced stress and organ dysfunction.