Effects of cisplatin on erythropoietin production in rats.
The effects of cisplatin on erythropoietin (EPO) production were investigated in comparison with the effects of phenylhydrazine in rats. Cisplatin (4.5 mg/kg i.p. bolus) decreased red blood cell count (RBC), hematocrit (Hct) and hemoglobin concentration (Hgb) for 14 days after dosing. These decreases were accompanied with increases of blood urea nitrogen (BUN) and serum creatinine (s-CRE). Both serum EPO concentration and kidney EPO mRNA content were significantly decreased in cisplatin-treated rats. On the other hand, phenylhydrazine (10 mg/kg p.o. once a day for 8 days) decreased RBC, Hct and Hgb, and increased serum EPO concentration and kidney EPO mRNA content. Phenylhydrazine had little effect on BUN or s-CRE. These results suggest that a suppression of EPO production is involved in the pathophysiology of cisplatin-induced renal anemia and that measurement of serum EPO concentration and kidney EPO mRNA content is available for distinguishing renal anemia from hemolytic anemia.
Toxicology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan.
A
A
Unami
N
N
Nishina
T
T
Terai
S
S
Sato
T
T
Tamura
K
K
Noda
Y
Y
Mine
D000740:Anemia / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D001806:Blood Urea Nitrogen; D002945:Cisplatin / Q000633:toxicity*; D003404:Creatinine / Q000097:blood; D004906:Erythrocyte Count / Q000187:drug effects; D004921:Erythropoietin / Q000096:biosynthesis* / Q000097:blood; D006400:Hematocrit; D006454:Hemoglobins / Q000187:drug effects; D007124:Immunoenzyme Techniques; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007674:Kidney Diseases / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology; D008297:Male; D010659:Phenylhydrazines; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014158:Transcription, Genetic
D000970:Antineoplastic Agents; D006454:Hemoglobins; D010659:Phenylhydrazines; D012333:RNA, Messenger; C030299:phenylhydrazine; D004921:Erythropoietin; D003404:Creatinine; D002945:Cisplatin