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

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          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.

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          Most cited references35

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          Mechanisms of Cisplatin Nephrotoxicity

          Cisplatin is a widely used and highly effective cancer chemotherapeutic agent. One of the limiting side effects of cisplatin use is nephrotoxicity. Research over the past 10 years has uncovered many of the cellular mechanisms which underlie cisplatin-induced renal cell death. It has also become apparent that inflammation provoked by injury to renal epithelial cells serves to amplify kidney injury and dysfunction in vivo. This review summarizes recent advances in our understanding of cisplatin nephrotoxicity and discusses how these advances might lead to more effective prevention.
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            Biological effects of resveratrol.

            L Frémont (2000)
            Resveratrol (3, 4', 5 trihydroxystilbene) is a naturally occuring phytoalexin produced by some spermatophytes, such as grapevines, in response to injury. Given that it is present in grape berry skins but not in flesh, white wine contains very small amounts of resveratrol, compared to red wine. The concentrations in the form of trans- and cis- isomers of aglycone and glucosides are subjected to numerous variables. In red wine, the concentrations of the trans-isomer, which is the major form, generally ranges between 0.1 and 15 mg/L. As phenolic compound, resveratrol contributes to the antioxidant potential of red wine and thereby may play a role in the prevention of human cardiovascular diseases. Resveratrol has been shown to modulate the metabolism of lipids, and to inhibit the oxidation of low-density lipoproteins and the aggregation of platelets. Moreover, as phytoestrogen, resveratrol may provide cardiovascular protection. This compound also possesses anti-inflammatory and anticancer properties. However, the bioavailability and metabolic pathways must be known before drawing any conclusions on the benefits of dietary resveratrol to health.
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              Resveratrol scavenges reactive oxygen species and effects radical-induced cellular responses.

              Scavenging or quenching of the reactive oxygen species (ROS) involved in oxidative stress has been the subject of many recent studies. Resveratrol, found in various natural food products, has been linked to decreased coronary artery disease and preventing cancer development. The present study measured the effect of resveratrol on several different systems involving the hydroxyl, superoxide, metal/enzymatic-induced, and cellular generated radicals. The rate constant for reaction of resveratrol with the hydroxyl radical was determined, and resveratrol was found to be an effective scavenger of hydroxyl, superoxide, and metal-induced radicals as well as showing antioxidant abilities in cells producing ROS. Resveratrol exhibits a protective effect against lipid peroxidation in cell membranes and DNA damage caused by ROS. Resveratrol was also found to have a significant inhibitory effect on the NF-kappaB signaling pathway after cellular exposure to metal-induced radicals. It was concluded that resveratrol in foods plays an important antioxidant role.
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                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                21 November 2018
                2018
                : 9
                : 1268
                Affiliations
                [1] 1Department of Pathology, College of Veterinary Medicine, King Faisal University , Al-Hasa, Saudi Arabia
                [2] 2Department of Pathology, College of Veterinary Medicine, Suez Canal University , Ismailia, Egypt
                [3] 3Faculty of Medicine, Ain Shams University , Cairo, Egypt
                [4] 4Department of Pharmacology, Faculty of Veterinary Medicine, Suez Canal University , Ismailia, Egypt
                Author notes

                Edited by: Paola Patrignani, Università degli Studi G. d’Annunzio Chieti e Pescara, Italy

                Reviewed by: Marta Chagas Monteiro, Universidade Federal do Pará, Brazil; Mohamed Aboubakr, Benha University, Egypt

                These authors have contributed equally to this work and share first authorship

                This article was submitted to Inflammation Pharmacology, a section of the journal Frontiers in Pharmacology

                Article
                10.3389/fphar.2018.01268
                6258716
                e00244eb-bc6e-4ca0-ae33-9b3a67f5b99a
                Copyright © 2018 Ibrahim, Al-Hizab, Abushouk and Abdel-Daim.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 11 September 2018
                : 17 October 2018
                Page count
                Figures: 6, Tables: 1, Equations: 0, References: 51, Pages: 9, Words: 0
                Categories
                Pharmacology
                Original Research

                Pharmacology & Pharmaceutical medicine
                benzyl isothiocyanate,cisplatin,kidney,resveratrol,mice
                Pharmacology & Pharmaceutical medicine
                benzyl isothiocyanate, cisplatin, kidney, resveratrol, mice

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