Possible mechanism for the anaemia induced by gentamicin in rats

Abstract

Getamicin, was administered subcutaneously to 6-week-old male F344/M rats at a dose of 100 mg/kg/day for 3 weeks, and the possible mechanism for gentamicin-induced anaemia was investigated. In the dosing group, the erythrocyte count, haematocrit value and haemoglobin concentration were decreased by 15%-17% compared with the values in the control group at the end of the dosing period. The reticulocyte count and plasma erythropoietin (Epo) level were decreased on days 7 and 14. No evidence of haemorrhage, haemolysis or compensatory erythropoiesis was observed in haematology, blood chemistry, gross pathology, organ weights or histopathology. Erythrocyte morphology and osmotic fragility showed no treatment-related changes. On the other hand, histopathological examination of the kidney revealed necrosis and regeneration of the renal tubules on days 14 and 21, suggesting extensive renal injury. Hypocellularity in the bone marrow was seen on day 21, and slightly decreased extramedullary haematopoiesis in the spleen was seen on day 14. It was considered that Epo production was suppressed because the renal peritubular cells are thought to be the site of Epo production. These results suggest that the major cause of the anaemia induced by gentamicin treatment is Epo deficiency following injury to the kidney, the site of Epo production.