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.
Department of Physiological Sciences, Obafemi Awolowo University, Ile-Ife, Osun State, Nigeria. stolakin@yahoo.co.uk
Akinsomisoye Olumide
AO
Stephen
Raji
R
Yinusa
D000818:Animals; D000962:Antimalarials / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004822:Epididymis / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005298:Fertility / Q000187:drug effects*; D015870:Gene Expression / Q000187:drug effects; D005837:Genitalia, Male / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006065:Gonadotropins, Pituitary / Q000097:blood; D008297:Male; D008856:Microscopy, Fluorescence; D009929:Organ Size / Q000187:drug effects; D002727:Proguanil / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012708:Sertoli Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013091:Spermatogenesis / Q000187:drug effects / Q000235:genetics; D013094:Spermatozoa / Q000187:drug effects / Q000473:pathology; D013737:Testis / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013739:Testosterone / Q000097:blood; D013997:Time Factors; D036401:Toxicity Tests, Chronic
D000962:Antimalarials; D006065:Gonadotropins, Pituitary; D013739:Testosterone; D002727:Proguanil