Leuprolide acetate prevents toxic effects of cisplatin on the kidneys and gastrointestinal tract.
We examined the protective effects of medical castration by means of gonadotropin-releasing hormone analogue (GnRHA) on the toxic effects of cisplatin in rats. Twelve days after a s.c. injection of a slowly-releasable form of leuprolide acetate (GnRHASR), rats were injected i.p. with cisplatin daily (3 mg/kg body weight (BW) for males and 4 mg/kg BW for females) for four days and sacrificed 24 h after the last injection. The doses caused acute tubular necrosis and gastrointestinal (GI) symptoms, i.e., diarrhea and fluid retention and bleeding in GI tract. GnRHASR pretreatment reduced serum urea nitrogen (SUN) and serum creatinine (SCre) increase and the incidence of GI symptoms. Histological analysis showed that rats pretreated with GnRHASR had noticeably less kidney damage. GnRHA thus demonstrated its ability to protect the kidneys and GI tract against cisplatin toxicity in both male and female rats. This finding suggests a potential clinical application of GnRHA in antineoplastic chemotherapy.
Nomura
K
K
Department of Medicine, Tokyo Women's Medical College, Japan.
Ando
T
T
Demura
H
H
D000818:Animals; D002945:Cisplatin / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced / Q000517:prevention & control*; D007674:Kidney Diseases / Q000139:chemically induced / Q000517:prevention & control*; D016729:Leuprolide / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344
D016729:Leuprolide; D002945:Cisplatin