Abstract

BackgroundCisplatin (CP) or cis-diammine dichloroplatinum (II) is a platinum based standard antineoplastic drug which is used against variety of solid tumors and neoplasms. The present study aimed to evaluate the shielding effects of rutin against CP induced testicular toxicity in rats.Methods28 male rats were divided into four groups. First group was given saline orally while second group received intra-peritoneal (i.p) injection of cisplatin (7 mg/kg) on day first and received saline for next 13 days. Third group received i.p injection of cisplatin at day one and treated with rutin (75 mg/kg) orally for next 13 days. Fourth group was treated with rutin orally for 13 days. Animals were sacrificed on 14th day and reproductive organs were analyzed for various parameters.ResultsCisplatin treatment resulted in a significant decrease in daily sperm production, decrease in head length and % DNA in head, reduction of epithelial cell height, tubular diameter, reduction of the number of spermatogonia, spermatocytes and spermatids, increase in the thiobarbituric acid reactive substances (TBARS) and oxidative stress in testicular tissues, and change of the intra-testicular testosterone concentrations. Rutin co-treatment resulted in reversing cisplatin effect on DNA damage, sperm count, histological and biochemical parameters.ConclusionThese results indicated that rutin co-treatment could ameliorate cisplatin-induced reproductive toxicity in male rats.

Highlights

  • Cisplatin (CP) or cis-diammine dichloroplatinum (II) is a platinum based standard antineoplastic drug which is used against variety of solid tumors and neoplasms

  • Third group of rats was injected with CP (7 mg/kg) at first day followed by daily oral dose of rutin dissolved in normal saline (0.9% saline), throughout the experimental period

  • Sperm production (DSP) A significant decrease (p < 0.01) in daily sperm production × 105 and efficiency of daily sperm production × 105 was observed in CP-treated group vs the control group

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Summary

Introduction

Cisplatin (CP) or cis-diammine dichloroplatinum (II) is a platinum based standard antineoplastic drug which is used against variety of solid tumors and neoplasms. The present study aimed to evaluate the shielding effects of rutin against CP induced testicular toxicity in rats. It is generally accepted that CP is a DNA alkylating agent that kills cells by several mechanisms including DNA damage, production of reactive oxygen species (ROS), and inducing apoptosis [1,2,3]. Rutin is widely present in plants but is relatively rare in their edible parts It was first discovered in nineteenth century in buckwheat which contain approximately 2– 10% of total dry weight and 15% in young leaves. The pharmacokinetics study of rutin (0.2080, 1.664 and 4.160 μg·ml− 1) in rat plasma showed that it is more stable and less degradable under different conditions [14]. Cisplatin involve c-Jun N-terminal kinases (JNK-mediated) apoptosis, inhibitor of apoptosis proteins (IAP) and c-FLIPL degradation, Ripoptosome formation and autophagy-mediated apoptosis [21]

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