Reversal of the toxic effects of cyclosporine on male reproduction and kidney function of rats by simultaneous administration of hCG + FSH.
We have shown earlier that the administration of cyclosporine impairs testicular function and causes a decrease in sperm counts, sperm motility and fertility. In order to determine whether or not the deleterious effects of CsA could be reversed by hormonal therapy, we injected sexually mature male Sprague Dawley rats with cremaphor + saline or CsA (40 mg./kg./d) alone or in combination with human chorionic gonadotropin (hCG; five micrograms./d/rat) and follicle stimulating hormone (FSH; five micrograms./d/rat). The injections were given subcutaneously for 14 days. As expected, CsA administration decreased the body and reproductive organ weights, testicular and epididymal sperm counts, sperm motility and fertilizing ability. Serum levels of LH were elevated and testosterone was decreased. The administration of FSH + hCG to the CsA treated rats restored the body and reproductive organ weights, sperm counts and motility. Seventy five percent of gonadotropin treated males were fertile as compared to 25% in the CsA treated group. In the hormone treated group, the blood levels of CsA were 50% of that of CsA treated group. In order to verify whether or not the decline in the blood levels of CsA was the cause for the amelioration of CsA-induced changes in the reproductive function, we compared the CsA + hormone treated group with another group treated with five mg./kg./d CsA which had blood levels of CsA comparable to the former group. In the five mg./kg./d group the reproductive functions were significantly lower than the CsA + hormone treated group suggesting, therefore, that the restoration of reproductive functions in the CsA + hormone treated group is a result of hormonal treatment. Administration of CsA (40 mg./kg./d) reduced the kidney weight and increased the levels of serum creatinine: these changes were also ameliorated by the administration of hCG + FSH.
Seethalakshmi
L
L
Division of Urologic Transplantation and Surgery, University of Massachusetts Medical Center, Worcester 01655.
Flores
C
C
Diamond
D A
DA
Menon
M
M
D000818:Animals; D006063:Chorionic Gonadotropin / Q000627:therapeutic use*; D003524:Cyclosporins / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D004359:Drug Therapy, Combination; D005298:Fertility / Q000187:drug effects*; D005640:Follicle Stimulating Hormone / Q000627:therapeutic use*; D005837:Genitalia, Male / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013094:Spermatozoa / Q000187:drug effects; D013739:Testosterone / Q000097:blood
D006063:Chorionic Gonadotropin; D003524:Cyclosporins; D013739:Testosterone; D005640:Follicle Stimulating Hormone