Reprotoxic activities of vildagliptin administration in male Wistar rats

Vildagliptin is an oral hypoglycemic agent used in the management of diabetes. Some oral antidiabetic drugs have been implicated in reproductive toxicity.The objective of this study was to investigate the effects of daily administration of vildagliptin at different dosages (0.35 mg/kg B.W., 0.70 mg/kg B.W. and 1.40 mg/kg B.W.) to male Wistar rats for 8 weeks. Sperm parameters, serum concentrations of testosterone, follicle stimulating hormone and luteinizing hormone and the histology of the testis of the rats were assessed. Another set of rats were also treated for 8 weeks and allowed to recover and the same parameters were assessed in them. Fertility study was conducted by determining their litter size. The results showed that vildagliptin administration significantly reduced sperm count and motility of the treated rats. It also significantly increased the number of abnormal sperms. Serum level of testosterone was significantly decreased while luteinizing hormone and follicle stimulating hormone levels showed no significant change. The histoarchitecture of the testis of the treated rats appeared visibly normal. The litter size was also significantly reduced. Most of the changes observed were dose dependent. However, these parameters were restored towards normal in the recovery group. Our results suggest that vildagliptin adversely affected sperm parameters, affected litter size and disrupted the pituitary - gonadal axis. These changes were however reversed upon cessation of drug administration.

Prolonged administration of proguanil induces reproductive toxicity in male rats.

The toxicity of proguanil was studied on reproductive activities in male rats using in vivo and in vitro methods. Groups of ten to twelve-week-old rats were administered proguanil (2.9 mg/kg body weight) daily for 5 days and 6 weeks respectively. Thereafter, body and reproductive organ weights were taken, sperm parameters were analyzed, while the histology of the testis and epididymis were carried out. Also, serum levels of testosterone, luteinizing hormone and follicle stimulating hormone were determined. Sertoli cells obtained from sixteen to eighteen day-old-rats were cultured and treated with 0.3 µM to 10 µM of proguanil for 5 days after which Sertoli cell viability and nuclei integrity were determined. Also, the genetic expressions of transferrin and Glial cell line-derived neurotrophic factor (G.D.N.F.) were assessed. The data obtained were analyzed using the analysis of variance (ANOVA) with Students-Newman-Keuls multiple comparison test. The results showed duration dependent significant decrease in body and organ weights and also in sperm parameters. Serum testosterone level was significantly decreased while luteinizing hormone and follicle stimulating hormone showed no significant change. Duration dependent degeneration was also observed in the testis and epididymis of treated rats. These changes were restored in recovery experiment. Viability and DNA integrity of treated Sertoli cells reduced in a dose and duration dependent manner. However, the genetic expressions of transferrin and Glial cell line-derived neurotropic factor were normal. These results show that proguanil could induce infertility in rats which may act by distorting the blood-testis barrier formed by the Sertoli cells.