Effect of indomethacin on red cell volume, iron kinetics and red cell survival in mice.

The time-response curve for hematocrit following s.c. injection of 400 microgram of indomethacin (IM) in a single dose into adult female mice showed a maximal depression at 3 days after IM with return to normal values by 11-12 days. The effect was dose-related showing a plateau with doses of IM above 400 microgram. The total circulating red cell volume was 68% of control and the plasma volume 117% of control 3 days after IM injection, recovering thereafter. At the same time, erythroid tissue iron uptake (microgram/h) was 67% higher in IM-treated than in non-injected mice. In mice with suppressed erythropoiesis due to daily i.p. injections of 0.06 microgram/g of actinomycin D, injection of IM induced a marked and rapid loss of cells from the circulation. Macroscopic and microscopic examinations of IM-treated mice at autopsy showed no indication of internal bleeding or other abnormalities. Serum non-conjugated bilirubin concentration was 2.2 times higher in IM-injected mice than in controls 3 days after drug administration. These results indicate that IM injection into mice in the experimental conditions reported here appears to induce a transient hemolytic state which is responsible for the depression of the red cell mass and the subsequent increase in the erythropoietic rate to compensate it. Both the decreased red cell volume and the increased plasma volume are responsible for the depression of the hematocrit value.