Hypoxia-induced megaloblastosis in vitamin B12-deficient rats

In rats, in contrast with human subjects who develop megaloblastic anaemia due to vitamin B-12 deficiency, haematological abnormalities with anaemia were not observed under normoxic conditions even though plasma vitamin B-12 concentration was reduced to <15 % of a normal concentration by depleting dietary vitamin B-12. To elucidate whether erythropoiesis was affected by vitamin B-12 deficiency in rats, these vitamin B-12-deficient rats were exposed to hypoxia (10.5 % O-2) to stimulate erythropoiesis. In the vitamin B-12-sufficient control rats, erythrocyte count was significantly (P<0.05) increased 1 week after starting the hypoxic exposure. However, the hypoxia-induced erythropoiesis was affected by vitamin B-12 deficiency, and no significant increase in the erythrocyte count was observed even after 6-week exposure to hypoxia in the vitamin B-12-deficient rats. In the vitamin B-12-deficient rats in hypoxia, erythrocytes became abnormally enlarged, and haemoglobin concentration in peripheral blood was increased in proportion to the increase of mean corpuscular volume. However, the level of the increase in the haemoglobin concentration was significantly (P<0.05) lower in the vitamin B-12-deficient rats compared with that in the -sufficient controls. In addition, in the vitamin B-12-deficient rats, in contrast to the -sufficient rats, serum erythropoietin concentration was not normalized even after 6-week exposure to hypoxia. These results indicate that a megaloblastic anaemia-like symptom is induced when the vitamin B-12-deficient rats are exposed to hypoxia.