Phenethyl isothiocyanate protects against cyclophosphamide-induced nephrotoxicity via nuclear factor E2–related factor 2 pathway in rats

Abstract

Phenethyl isothiocyanate (PEITC), a secondary metabolite in Cruciferous plants, exerts chemopreventive and antioxidant effects. However, its therapeutic potential in cyclophosphamide (CP)-induced nephrotoxicity is not clear. So, we focused to research on the effect of PEITC against renal toxicity caused by CP and its relationship to the Nrf2 signaling mechanism. Thirty female Wistar albino rats were allocated to three groups: control (n = 10), CP (n = 10), and PEITC-pretreated group (150 µmol/kg b.w. orally; n = 10). The antioxidant enzyme activities and levels of malondialdehyde (MDA), sirtuin 1 (SIRT1), glutathione-S-transferase (GST), nuclear factor E2–related factor 2 (Nrf2), nuclear factor kappa B (NF-κB), serum urea, and creatinine (Cr) were measured. In the CP group, serum urea and Cr, MDA, and NF-κB levels have risen, and the activities of antioxidant enzymes and SIRT1, Nrf2, and GST levels have reduced significantly (P < 0.05). PEITC diminished levels of Cr, urea, MDA, and NF-κB while it enhanced antioxidant enzyme activities and GST, Nrf2, and SIRT1 levels significantly (P < 0.05). Pretreatment with PEITC ameliorated kidney tissue injury. The renal protective effect of the PEITC was supported by the histological analysis of the kidney. PEITC prevented CP-induced nephrotoxicity by decreasing oxidative damage through Nrf2 and SIRT1 activation and NF-κB inhibition. Therefore, we have suggested that PEITC may be a useful agent for protection against CP-induced renal injury.