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 decrease...

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Bibliographic Details
Published in:Journal of toxicological sciences 1996/08/25, Vol.21(3), pp.157-165
Main Authors: UNAMI, Akira, NISHINA, Noriko, TERAI, Takao, SATO, Susumu, TAMURA, Takayuki, NODA, Kohsei, MINE, Yasuhiro
Format: Article
Language:English
Subjects:
Anemia - blood
Anemia - chemically induced
Anemia - physiopathology
Animals
Antineoplastic Agents - toxicity
Biological and medical sciences
Blood Urea Nitrogen
Cisplatin
Cisplatin - toxicity
Creatinine - blood
Drug toxicity and drugs side effects treatment
Erythrocyte Count - drug effects
Erythropoietin - biosynthesis
Erythropoietin - blood
Hematocrit
Hemoglobins - drug effects
Immunoenzyme Techniques
Kidney - drug effects
Kidney - metabolism
Kidney Diseases - blood
Kidney Diseases - chemically induced
Kidney Diseases - physiopathology
Male
Medical sciences
Pharmacology. Drug treatments
Phenylhydrazines
Polymerase Chain Reaction
Rats
Rats, Sprague-Dawley
RNA, Messenger - metabolism
Toxicity: blood
Transcription, Genetic
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Summary: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.
ISSN:0388-1350
1880-3989
DOI:10.2131/jts.21.3_157