Ameliorative Role of Grape Seed Extract (Vitis Vinifera) on Gemcitabine- Induced Testicular Damage in Rabbits

Spermatogenesis is a highly conserved and regulated process and it is sensitive to fluctuations in the physical and chemical environment. Gemcitabine is a novel antimetabolic anticancer drug used frequently in the treatment of many cancers. Gemcitabine may disrupt spermatogenesis by targeting various testicular cell types. Grape seed extract is a natural product, recently identified as one of the most powerful antioxidants. In addition, it has been reported to exert anticarcinogenic effects.

This current work aimed to study the effect of gemcitabine on the testicular tissue of local adult rabbits and to evaluate the possible protective role of Grape seed extract.

A experimental study was performed on twenty seven  adult male local rabbits, were divided into three  groups,  nine rabbit in each group as following: group (A): animals of control group received normal saline injection,  group (B): animals of treated group received therapeutic dose of gemcitabine alone in a dose of 25 mg/kg body weight intraperitoneally once per week for six successive weeks and group (C): served as protective group and was concomitantly treated with grape seeds extract by oral gavages in a dose of 250 mg/kg body weight  and gemcitabine in a dose of 25 mg/kg body weight intraperitoneally once per week for six successive weeks.

The results of the present investigation showed that gemcitabine toxicity produced significant structural changes in the testis of group B, gemcitabine treated group, in the form of multiple distortion of the seminiferous tubules, with cellular disorganization, testicular tubular cell degeneration, necrosis, tubular atrophy, desquamation and sloughing of the seminiferous epithelium which was accumulated in the centre of the seminiferous tubules in the form of degenerated tissue.  Many seminiferous tubules showed widely spaced spermatogenic cells. Karyopyknosis, disappearance of interstitial cells of Leydig and necrotic Sertoli cells, progressive tubular and interstitial testicular damage together with spermatogenic arrest was an initial necrotic change induced by gemcitabine exposure. Disorganization of spermatogenic cells, an interruption in spermatogenesis process and the seminiferous tubules are devoid of sperms was also showed in this study.

Sections from the testes of animals received therapeutic dose of gemcitabine and treated by grape seed extract, group (C) were showing partial preservation of the normal structure of the seminiferous tubules. Most of them more or less resembled the normal structure.

It could be concluded that gemcitabine caused marked alterations in the structure of the seminiferous tubules of the rabbit testis that may be minimized by administration of grape seed extract. Our findings simply revealed that grape seeds extract treatment significantly inhibits testicular cell apoptosis, which suggests that apoptosis may be one of the underlying mechanisms by which grape seeds extract protects against gemcitabine induced defective spermatogenesis.