Phenethyl isothiocyanate alleviates renal injury in STZ‐induced diabetic rats: Effect on oxidative stress, glycative stress and inflammation

Abstract

Background Diabetic nephropathy (DN) is a serious microvascular complication of diabetes mellitus (DM) and the major cause of end-stage renal disease. The pathogenesis of DN is multifactorial. Indeed, advanced glycation end products, inflammation and oxidative stress were shown to significantly contribute to DN development/progression. Aim of the work Given the reported beneficial biological effects of phenethyl isothiocyanate (PEITC), the present study aims to evaluate the potential protective effects of PEITC in streptozotocin (STZ)-induced diabetic Sprague Dawley rats. Methods PEITC was administrated at 3, 10, 30 mg/kg/day for 8 weeks after confirming experimental induction of DM. Renal function (creatinine, urea, proteinuria), hypertrophy index, inflammation (NLRP3/TXNIP/Caspase-1 and pro-inflammatory cytokines IL-1β,TNF-α, IL-6), redox homeostasis (Nrf2/Keap1/HO1/γGCS, lipid peroxidation, total antioxidant capacity, and antioxidants GSH, SOD) and protein glycation (AGE/RAGE/GLO1) were assessed by spectrophotometry, ELISA and immunohistochemistry. Moreover, renal structural and ultra-structural alterations were evaluated. Results According to our results, PEITC administration improved renal function, restored oxidant/antioxidant balance, diminished TXNIP/NLRP3-dependent inflammation and suppressed glycative stress in a dose dependent manner. Furthermore, results from histological and electron microscopy studies revealed preservation of renal structure by PEITC treatment. Conclusion These findings underline for the first time that PEITC confers a considerable protection against diabetes-induced kidney injury, suggesting potential use of PEITC as early therapeutic intervene that might slow down the progression of DN via multifactorial pathways targeting.