Effect of recombinant human erythropoietin on new anaemic model rats induced by gentamicin.
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.
Nagano
N
N
Pharmaceutical Laboratory, Kirin Brewery Co. Ltd., Gunma, Japan.
Koumegawa
J
J
Arai
H
H
Wada
M
M
Kusaka
M
M
D000740:Anemia / Q000139:chemically induced* / Q000188:drug therapy; D000818:Animals; D001810:Blood Volume / Q000187:drug effects; D004921:Erythropoietin / Q000097:blood / Q000172:deficiency / Q000627:therapeutic use*; D005839:Gentamicins / Q000633:toxicity*; D006400:Hematocrit; D007683:Kidney Tubular Necrosis, Acute / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D009996:Osmotic Fragility / Q000187:drug effects; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000627:therapeutic use; D013154:Spleen / Q000187:drug effects* / Q000473:pathology; D014511:Uremia / Q000139:chemically induced* / Q000188:drug therapy
D005839:Gentamicins; D011994:Recombinant Proteins; D004921:Erythropoietin