Preventive effect of zelandopam, a dopamine D1 receptor agonist, on cisplatin-induced acute renal failure in rats.
To elucidate the role of peripheral dopamine D1 receptors in cisplatin-induced acute renal injury, effect of zelandopam (YM435, (-)-(S)-4-(3,4-dihydroxyphenyl)-7,8-dihydroxy-1,2,3,4-tetrahydroisoquinoline hydrochloride hydrate), a selective renal dopamine D1 receptor agonist, on cisplatin-induced acute renal failure in rats was studied. Rats were divided into six groups: control, cisplatin and cisplatin plus zelandopam (30, 100, 300 mg/kg p.o. twice, 75 and 15 min before cisplatin injection) or the free radical scavenger CV-3611 (2-O-octadecylascorbic acid, 10 mg/kg p.o., 75 min before cisplatin injection) treated groups. Rats received intraperitoneal injection of cisplatin at a dose of 5 mg/kg. Four days after cisplatin injection, plasma creatinine, blood urea nitrogen and body weight were measured and the kidneys were removed for histological examination. Cisplatin induced acute renal failure characterized by the increases in plasma creatinine and blood urea nitrogen with tubular damage, and decreased body weight. Zelandopam dose-dependently prevented all these changes. The free radical scavenger CV-3611 significantly attenuated a decrease in body weight and renal dysfunction without reducing tubular damage. The present study is the first demonstration for that a selective dopamine D1 receptor agonist is effective in preventing acute renal failure induced by cisplatin.
Yatsu
Takeyuki
T
Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co, Ltd, 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan. yatsu@yamanouchi.co.jp
Aoki
Motonori
M
Inagaki
Osamu
O
D058186:Acute Kidney Injury / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D000818:Animals; D001205:Ascorbic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D001806:Blood Urea Nitrogen; D001835:Body Weight / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage; D003404:Creatinine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D007546:Isoquinolines / Q000494:pharmacology*; D007684:Kidney Tubules / Q000187:drug effects / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000819:agonists*; D044005:Tetrahydroisoquinolines
D007546:Isoquinolines; D017447:Receptors, Dopamine D1; D044005:Tetrahydroisoquinolines; C061185:2-O-octadecylascorbic acid; D003404:Creatinine; C073504:zelandopam; D001205:Ascorbic Acid; D002945:Cisplatin