Quercitrin, a natural flavonoid glycoside, protects against cisplatin‐induced injury in rats without hindering cisplatin beneficial cytotoxic activity

Abstract

Objectives The present study aimed to evaluate the possible nephroprotective and hepatoprotective effects of quercitrin (a natural flavonoid glycoside) against cisplatin‐induced toxicity in rats. The study extended to evaluate the effect of quercitrin on the beneficial cytotoxic activity of cisplatin. Background Cisplatin is a widely used cytotoxic agent whose benefits are limited by its nephrotoxic and hepatotoxic potentials. Quercitrin has a wide variety of pharmacological actions including anti ‐ oxidant, anti‐inflammatory and immunomodulatory activities. Methods Cisplatin toxicity was induced by a single 7.5 mg/kg i.p injection. Quercitrin (10 and 20 mg/kg) was orally administrated for 1 week starting one day before cisplatin. Assessment of cisplatin injury was performed by measuring serum creatinine (Cr) and blood urea nitrogen (BUN) as renal injury markers, while serum alanine transaminase (ALT) and aspartate transaminase (AST) were assessed as hepatic injury markers. In addition, serum total cholesterol (TC) and triglycerides (TG) were determined as dyslipidemic markers. Renal and hepatic tissue malondialdehyde (MDA), reduced glutathione (GSH) and total nitrate/nitrite (NOx) levels were measured as oxidative and inflammatory markers., Western blot analysis of renal and hepatic phospho‐Akt (p‐Akt) and nuclear factor‐kappa B (NF‐κB) expression were determined as tissue inflammatory and immunological markers, coupled with histopathological examination of renal and hepatic tissues. Animal handling protocol was approved by Ethics Committee of the Faculty of Pharmacy, Beni‐Suef University, following guidelines of the National Institute of Health (NIH) Guide for Care and Use of Laboratory Animals. Results Quercitrin significantly ameliorated cisplatin‐induced renal and hepatic injury evidenced by corrections of serum Cr, BUN, ALT, AST, TC and TG levels as well as renal and hepatic MDA, GSH, NOx contents and p‐Akt and NF‐κB expression levels, in addition to correction of histopathological alterations. Cytotoxicity assay on breast adenocarcinoma (MCF‐7) cells using the thiazolyl blue tetrazolium bromide (MTT) revealed that quercitrin did not inhibit the cytotoxic activity of cisplatin in vitro . Conclusions Our data showed the ability of quercitrin to protect against cisplatin‐induced nephrotoxicity, hepatotoxicity and dyslipidemia without interfering with Cisplatin's beneficial anticancer activity, suggesting the effective use of quercitrin during cisplatin course treatment permitting dose scaling required in some resistant cancer types.