Abstract

The aim of this study is to examine the protective effect of naringenin-oxime (NOX) on cisplatin-induced major organ toxicity and DNA damage in rats. Thirty-five male Wistar albino rats were equally split into five groups as follows: control (i.p., 0.1 ml of saline), Cis administration (i.p., 7 mg/kg b.w.), NOX treatment (i.p., 20 mg/kg b.w., daily for ten days), Cis + NOX20, and Cis + NOX40 combination (i.p., 20 and 40 mg/kg b.w., daily for ten days). Serum and peripheral blood mononuclear leukocytes (PBMC) were obtained from blood. Malondialdehyde, glutathione, total antioxidant and oxidant status, and catalase were measured in serum, liver, and kidney, and oxidative stress index was calculated. In parallel, paraoxonase and arylesterase activities were tested in liver and serum. We used 8-OHdOG as a marker for DNA damage in serum via ELISA and in PMBC via comet assay. Treatment with Cis elevated the levels of serum biochemical parameters, oxidative stress, and DNA damage. Pretreatments of NOX restored biochemical and oxidative stress parameters in serum, renal, and liver tissues (p < 0.01) and reduced 8-OHdG level, a finding further supported by comet assay in PBMC. Observations of the present study support the fact that treatment with NOX prevents Cis-induced hepatotoxicity, nephrotoxicity, and genotoxicity by restoring antioxidant system.

Highlights

  • Cisplatin (Cis) is a widely used chemotherapeutic agent in treatment regimens for some human malignant tumors [1, 2]

  • Malondialdehyde (MDA) level is commonly used as an indicator for measuring free radical induced by LPO

  • A statistically significant (p < 0.01) increase was detected in MDA levels of kidney, serum, and liver of rats administered with Cis when compared to the control group

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Summary

Introduction

Cisplatin (Cis) is a widely used chemotherapeutic agent in treatment regimens for some human malignant tumors [1, 2]. Increase in free radical production and decrease in antioxidant defense systems, involving antioxidant enzymes and nonenzymatic molecule called glutathione (GSH), have been shown to mediate the toxicity caused by Cis [11,12,13]. Those decrements may cause impairment in antioxidant defense mechanisms securing tissue harm, which are induced by free radicals, and mutagenic capacity of Cis. lipid peroxidation and DNA damage [14] which are formed in response to Cis administration are reported [15, 16]. There are many studies which demonstrated the use of antioxidants in mitigating the adverse effects related to Cis [1, 17, 19,20,21]

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