May-June 2019 Indian Journal of Pharmaceutical Sciences 514 Research Paper Vincristine (VCR) also known as leurocristine is a Vinca alkaloid derived from the Catharanthus roseus (Madagascar periwinkle) formerly Vinca rosea. VCR has been widely used as an anticancer drug because of its ability to inhibit cell division through prevention of polymerization of tubulin of the microtubules, which constitute the spindle fibre and the disassociation of the existing microtubules [1] . Although being a potent anticancer drug its use is limited due to a wide spectrum of side effects such as neurotoxicity, alopecia, colicky abdominal pain, myocardial infarction, optic atrophy and diplopia [2,3] . The male reproductive system consisted of actively dividing cells has also shown to be affected by VCR, thus compromising fertility [4] . Epididymis being the site for sperm maturation is very important for the development of mature and motile sperm with fertilizing ability. The array of proteins and ions in the epididymis plays a vital role in maintaining the epididymal function [5] ; even a slight modification would effects the metabolic pathways and ultimately result in compromised epididymal function. Several reports have suggested the impairment of epididymal functions and spermatogenesis on VCR administration [6] thereby affecting the levels of sperm maturation and transit proteins. It has also been shown that apart from conventional male reproductive toxicity assessment by measuring the weight of reproductive organs such as testis, epididymis and prostate, analysis of sperm motility and viability, macroscopic and histological examination and changes in hormone levels [7,8] , the protein profile can also be used to evaluate the male reproductive toxicity [9-12] . The present study was aimed to evaluate the alterations in the sperm count, ion concentration and pattern of protein profile in cauda and caput after treatment with VCR thus leading to compromised epididymal functions. MATERIALS AND METHODS Male Wistar rats of proven fertility weighing 150-200 g Epididymal Toxicity Associated with Vincristine Treatment T. SONAWANE*, S. AZAZ 1 , K. HEMANT 1 AND T. LIJI 1 Amity Institute of Biotechnology, Amity University, Mumbai-410 206, 1 School of Biotechnology and Bioinformatics, D. Y. Patil Deemed to be University, Mumbai-400 706, India Sonawane et al.: Epididymal Toxicity Associated with Vincristine Vincristine, a major player in front line combination chemotherapy of cancer reduces testosterone levels contributing to reproductive toxicity. Much is known about testicular toxicity of vincristine as compared to its effect on epididymis; hence, the present study aimed to evaluate the epididymal toxicity associated with vincristine treatment, which also contributes to the overall reproductive toxicity associated with vincristine. Vincristine was intraperitoneally injected to adult male Wistar rats of proven fertility with a dose of 40 mg/kg/day dissolved in 0.5 ml of physiological saline for 30 days. The epididymal weight was found to be unaltered after treatment whereas sperm count was reduced significantly. Significant changes were noted in ion concentrations of cauda and caput of epididymis with changes in protein profile of the tissue, sperm and luminal protein from cauda and caput region, which plays a significant role in sperm maturation and sperm transport. Infertility associated with vincristine could be attributed to its effects on various epididymal proteins involved in sperm protection and various stages of sperm development such as cytoplasmic extrusion and membrane stabilization, which had contributed to the abnormal sperm count and impaired function. Key words: Vincristine, epididymis, toxicity, ion concentration, sperm count *Address for correspondence E-mail: tdsonawane@mum.amity.edu This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms Accepted 20 April 2019 Revised 27 December 2018 Received 21 September 2018 Indian J Pharm Sci 2019;81(3):514-520