Abstract

Cisplatin is an effective chemotherapeutic drug used to treat many types of tumours. However, it may cause male reproductive toxicity. Gallic acid exhibits beneficial effects such as antioxidant, anti-inflammatory and antitumor. The current study investigated the beneficial effects of gallic acid against testis and epididymis toxicity induced by cisplatin. Male rats were divided into 4groups as follows (n=7): Control, cisplatin (a single dose of 8mg/kg), Gallic acid (50mg/kg) and cisplatin +Gallic acid groups. Testis was examined morphometrically by stereological methods. In addition, apoptosis, DNA damage, oxidative stress parameters in testis and testosterone in serum were measured. Epididymis was histopathologically evaluated. As a result, a significant decrease was observed in the number of spermatogonia, Leydig and Sertoli cells, testicular volume, height of germinal epithelial, Bcl-2 immunopositive cell number, activity of CAT, GSH and SOD enzymes and serum testosterone levels compared with the cisplatin group control group, while a significant increase was observed in the number of Caspase-3, Bax and 8-OHdG immunopositive cells and the MDA levels. However, Gallic acid significantly restored these parameters. Our study reveals that Gallic acid may improve Cisplatin-induced male reproductive toxicity by reducing oxidative stress, suppressing apoptosis and DNA damage and restoring structural and functional deterioration.

Highlights

  • Cisplatin (CP) is a powerful neoplastic drug widely used to improve various cancer such as bladder, lung, and testis cancer (Azarbarz et al 2020)

  • Our study reveals that Gallic acid (GA) may improve CP-induced male reproductive toxicity by reducing oxidative stress, suppressing apoptosis and DNA damage, and restoring structural and functional deterioration

  • Height of germinal epithelium significantly decreased in the CP group compared to the control group, while a significant increase was observed in the CP + GA group compared to the CP group (p < 0.05) (Table 1)

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Summary

Introduction

Cisplatin (CP) is a powerful neoplastic drug widely used to improve various cancer such as bladder, lung, and testis cancer (Azarbarz et al 2020). The testis has become the target of chemotherapeutic agents due to the occurrence of spermatogenesis and spermiogenesis, where testicular cell division and morphological changes occur, and these agents can damage the testis (Ceylan et al 2020). The permanent side effects of CP cause disruption of the Sertoli cell and seminiferous epithelium, resulting in impaired spermatogenesis (Whirledge et al 2015). CP causes epididymal toxicity resulting in decreased epididymal sperm count (Kohsaka et al 2020). The underlying mechanism of CP on the testis and epididymis is not fully understood, one of its basic mechanisms is estimated to be related to its induction of reactive oxygen species (ROS) production and the decrease in the level of testicular antioxidants (Eren et al 2020). Antioxidant and functional foodstuffs have been applied to reduce or prevent CP-induced toxicity (Kohsaka et al 2020)

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