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Al Mansoori, Al Shamri, Al Kendi, Al Jaberi, Sheikh, Amir, Nalin, and Ojha: Bisabolol ameliorates cisplatin-induced nephrotoxicity in rats

Introduction: Cisplatin (CSP) is a commonly used anticancer drug, but its notable side-effect (nephrotoxicity) limits its use in the clinic. Bisabolol (BSB), a natural monocyclic sesquiterpene alcohol, has garnered attention in recent years because of its antioxidant, anti-inflammatory and antitumorigenic activities.

Objectives: To investigate whether BSB can prevent the nephrotoxic effect of CSP in a clinically relevant murine model, and determine the mechanisms involved.

Material and methods: Male Wistar rats were randomly divided into four groups: Control group, BSB group, CSP group and CSP + BSB group. Intraperitoneal injection of CSP (6 mg/kg) was administered to induce nephropathy, in which the tubular injury is largely dependent on inflammation and oxidative/nitrative stress. The test drug, BSB, was given at 0, 3, 6, 9, 12, 24, 36, 48, 60, 72, 96 and 120 hours of the CSP injection, and on Day 5 rats were sacrificed following the final dose of BSB.

Results: CSP-induced injury of the renal tissue was evident from (i) histopathological damage of the renal tissues, (ii) increases in serum uric acid, urea and creatinine, (iii) increases in malondialdehyde (MDA) and nitric oxide (NO), (iv) decreases in the level of glutathione and activities of superoxide dismutase, catalase and reduced form of glutathione and (v) increases in the inflammatory cytokines (IL-1β, IL-6 and TNF-α). However, the BSB treatment significantly reduced oxidative/nitrosative stress and prevented the kidney dysfunction supported by preserved histopathological changes.

Conclusions: Based on present study findings, it can be concluded that BSB may be an excellent therapeutic agent to prevent CSP-induced nephrotoxicity. Given the wide beneficial effects and safety profile of BSB along with its antitumorigenic activity, BSB has tremendous therapeutic potential in a multitude of other diseases associated with inflammation and oxidative stress.

Acknowledgements: CMHS for funding the research grant and Dr Shreesh Ojha for supervising this project.

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