Nephroprotective Effects of Benzyl Isothiocyanate and Resveratrol Against Cisplatin-Induced Oxidative Stress and Inflammation.

Abdelazim Ibrahim,Fahad A. Al-Hizab,Abdelrahman Ibrahim Abushouk,Mohamed M. Abdel-Daim

doi:10.3389/fphar.2018.01268

Abdelazim Ibrahim, Fahad A. Al-Hizab + Show 2 more

Open Access

https://doi.org/10.3389/fphar.2018.01268

Copy DOI

Abstract

This study was performed to compare the nephroprotective effects of benzyl isothiocyanate (BITC) and resveratrol (RES) and investigate the nephroprotective efficacy of their combination against cisplatin-induced acute renal injury. Five animal groups (each of eight) received either normal saline, a single intraperitoneal injection of cisplatin (20 mg/kg) at the sixth day, cisplatin plus oral RES (30 mg/kg) or BITC (100 mg/kg in diet), or a combination of both for 10 days. Compared to saline-treated mice, cisplatin-intoxicated mice had significantly higher (p < 0.05) serum levels of urea, creatinine, interleukin-1β (IL-1β), and tumor necrosis factor-α. Moreover, biochemical analysis of kidney tissue homogenates showed that cisplatin intoxication was associated with significantly higher (p < 0.05) tissue levels of malondialdehyde (MDA) and lower levels of reduced glutathione and activities of endogenous antioxidant enzymes (glutathione peroxidase, superoxide dismutase, and catalase) in comparison to normal controls. Histopathological and immunohistochemical examinations of renal tissue slices from cisplatin-intoxicated mice showed interstitial leukocytic infiltration, tortuous tubules with vacuolated epithelium, luminal casts, and overexpression of cyclooxygenase-II enzyme. On the other hand, treatment with RES or BITC ameliorated all the previous parameters. The effects of both compounds were comparable in all assessed parameters, except IL-1β serum concentration and renal tissue MDA concentration (which were significantly lower in the RES group). Interestingly, treatment with BITC and RES combination restored the normal concentrations of all the aforementioned biochemical parameters, as well as near normal histological and immunohistochemical pictures. In conclusion, BITC exerted nearly comparable nephroprotective, antioxidant, and anti-inflammatory effects to RES and the combination of both agents showed more potent nephroprotective effects against cisplatin than each one alone.

Highlights

Cisplatin (Cis-diamminedichloroplatinum) is a potent chemotherapeutic drug (Figure 1A), used in the management of several malignancies, such as advanced bladder carcinoma and metastatic ovarian and testicular tumors (Galanski, 2006)
Cisplatin-intoxicated mice, treated by RES and benzyl isothiocyanate (BITC), alone or in combination, had significantly lower (p < 0.05) serum levels of the aforementioned parameters than those treated with cisplatin alone
The effects of both compounds were comparable in all assessed parameters, except IL-1β serum concentration

Summary

Introduction

Cisplatin (Cis-diamminedichloroplatinum) is a potent chemotherapeutic drug (Figure 1A), used in the management of several malignancies, such as advanced bladder carcinoma and metastatic ovarian and testicular tumors (Galanski, 2006). Its clinical use is restricted due to tumor resistance and major dose-related side effects, such as nephrotoxicity, ototoxicity, and bone marrow depression (Arany and Safirstein, 2003; Sastry and Kellie, 2005; Dasari and Tchounwou, 2014). With the early clinical application of cisplatin, more than 50% of patients reported dose-related renal insufficiency (Goldstein and Mayor, 1983); using saline hydration and diuresis during cisplatin administration reduced these rates to about 20% (Hartmann et al, 1999). Among the several mechanisms that were proposed for cisplatin-induced renal damage, the oxidative stress-mediated cytotoxicity has been prominent. Cisplatin directly interacts with glutathione (GSH), suppressing its antioxidant effect (Arany and Safirstein, 2003; Siddik, 2003)

Methods

Results

Conclusion