Protective effect of resveratrol in di-n-butyl phthalate-induced nephrotoxicity: Immunohistochemical and ultrastructural studies

Abstract

OBJECTIVE: To explore the renoprotective nature of resveratrol by assessing markers of antioxidant competence in di–n-butyl phthalate (DBP)–injured rat kidneys with immunohistochemistry and electron microscopic techniques and as well as biochemical analyses. STUDY DESIGN: A total of 36 adult female 20-day-old Wistar albino rats were given a diet containing either 500 mg/kg/day DBP (low-dose group) or 1,000 mg/kg/day DBP (high-dose group) dissolved in corn oil for 4 weeks. To study the potential protective effects of resveratrol and the effects of a solvent for resveratrol, other groups were used as controls and were given a solvent (carboxymethyl cellulose [CMC], 10 mL/kg), 500 mg/kg/day DBP+20 mg/kg/day resveratrol, or 1,000 mg/kg/day DBP+20 mg/kg/day resveratrol. RESULTS: DBP and CMC treatment increased renal lipid peroxidation significantly and decreased the RSH level. TEM and SEM results showed degenerative changes such as deletion, folding and thickening of basement membrane, appearance of electron-dense intramembranous and mesangial deposits, and deletion of foot processes in the high-dose DBP-treated group. Treatment with resveratrol led to an improvement in both biochemical and histological alterations induced by DBP or CMC. Immunohistochemical results also supported our electron microscopic findings. CONCLUSION: DBP caused renal toxicity by inducing lipid peroxidation and morphological alterations, and resveratrol protects against DBP-induced nephro-toxicity. (Anal Quant Cytopathol Histpathol 2017; 39:17–34) Keywords: butyl phthalate, CASP3, Caspase-3, di-n-butyl phthalate, ET1 protein, kidney, resveratrol, scanning transmission electron microscopy tomography, TEM tomography, transmission electron microscopy.