Vitamin D restores redox balance and modulates irisin and spexin expression in a rat model of streptozotocin-induced diabetic nephropathy

Background In the background Diabetic nephropathy (DN) is progressive complication of diabetes mellitus characterised by oxidative stress, altered metabolic regulation, and structural renal damage. Irisin and spexin are emerging peptide hormones involved in energy homeostasis and redox balance, and their role in DN remains insufficiently defined. This study therefore aims at investigating if vitamin D supplementation can attenuate the DN progression by regulating the expression of irisin and spexin toward their restoration to redox homeostasis. Method Thirty-two male Wistar rats were divided into four groups: control, vitamin D (50 IU/day), DN, and DN + vitamin D. DN was induced via streptozotocin (50 mg/kg, i.p.). After 8 weeks of vitamin D administration, renal function markers (creatinine, BUN, LDH), oxidative stress parameters (TOS, TAS), and level of irisin/spexin (serum and renal tissue) were assessed. Histopathological and immunohistochemical evaluations were performed to assess renal tissue injury and peptide localisation. Results Serum creatinine, BUN, LDH, and TOS increased significantly due in diabetic nephropathy. Moreover, the disease caused a decrease in TAS, irisin, and spexin (p < 0.05 vs control). The pathological changes were reversed with vitamin D supplementation, which also ameliorated renal histology and restored serum and kidney tissue levels of irisin and spexin (p < 0.05 vs DN). Immunohistochemistry analysis showed that the expression of these peptides was reduced in DN and partially restored by vitamin D. Conclusion The present discoveries reveal that vitamin D is described as renoprotective to diabetic nephropathy, purportedly by redox stabilization and upregulation of irisin and spexin. These peptides may become promising therapeutic targets or novel biomarkers in the pathophysiology of diabetic kidney disease.