Effect of Recombinant Human Erythropoietin on New Anaemic Model Rats Induced by Gentamicin

Author:

Nagano Nobuo1,Koumegawa Jun-Ichi1,Arai Hirofumi1,Wada Michihito1,Kusaka Masaru1

Affiliation:

1. Pharmaceutical Laboratory, Kirin Brewery Co. Ltd, 3 Miyahara-cho Takasaki-shi, Gunma 370-12, Japan

Abstract

Abstract The effects of recombinant human erythropoietin (r-HuEPO) on haematological parameters were studied in rats in which uraemia and anaemia had been induced by gentamicin, an aminoglycoside antibiotic and a nephrotoxic agent. After the occurrence of slight polycythaemia, the red blood cell count, haematocrit and haemoglobin concentration decreased by 20–30% compared with those of the control (saline-injected) rats. At the end of gentamicin treatment, the endogenous serum EPO level had decreased to about 40% compared with that of control rats. Gentamicin-treated rats showed marked elevation of blood urea nitrogen, extensive tubular necrosis in the kidney and haemosiderin deposition in the spleen. In the osmotic fragility test, the fragility of erythrocytes significantly increased compared with that of control rats. These findings indicate that the anaemia induced by gentamicin is due not only to a deficiency of EPO but also to an enhancement of fragility of erythrocytes in an azotaemic environment. The administration of r-HuEPO during anaemia markedly increased red blood cell count, haematocrit and haemoglobin concentration. It is suggested that a gentamicin-treated rat is a useful and convenient anaemic model and r-HuEPO is useful for treatment of anaemia in acute renal failure.

Publisher

Oxford University Press (OUP)

Subject

Pharmaceutical Science,Pharmacology

Reference28 articles.

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3. Decreased responsiveness of hematopoietic tissue to erythropoietin in acutely uremic rats;Bozzini;J. Lab. Clin. Med.,1966

4. Effect of gentamicin on renal function in the rat;Cohen;J. Pharmacol. Exp. Ther.,1975

5. Regulation of erythropoietin production is related to proximal tubular function;Eckardt;Am. J. Physiol.,1989

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