Effects of malotilate on rat erythrocytes.
Rats developed anemia during treatment with high doses of malotilate, a hepatotropic agent. A repeated dose of 1,000 mg/kg caused a 20-30% decrease in the number of red blood cells and in hematocrit and hemoglobin values within the first week. In response to the anemia, the reticulocyte count increased, and target cells, acanthocytes and Howell-Jolly bodies appeared in the peripheral blood. In the spleen, hemosiderin deposition was enhanced. The life span of 51Cr-labelled erythrocytes was shortened from 15 to 2 days in the high-dose group, whereas plasma iron disappearance and hemoglobin synthesis were significantly potentiated. Hemorrheological examinations revealed an increase in blood viscosity. Hemolytic resistance to mechanical stimuli was reduced, but that to osmotic stimuli was enhanced. At the same time as the onset of the anemia, serum and red cell membrane cholesterol and phospholipid began to increase on day 4 or 6. Incorporation of cholesterol into red cell membranes in vitro was significantly potentiated when serum obtained from rats after a single administration of 1,000 mg/kg was added to the culture. These results suggest that malotilate causes an increase in the surface area of the erythrocytes by accelerating the incorporation of cholesterol into their membranes, and such erythrocytes might be rheologically impaired and captured more easily by the spleen.
Akahane
K
K
Drug Safety Research Center, Research Institute, Daiichi Seiyaku Co., Ltd., Tokyo, Japan.
Furuhama
K
K
Inage
F
F
Onodera
T
T
D000740:Anemia / Q000139:chemically induced; D000818:Animals; D001809:Blood Viscosity / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D004907:Erythrocyte Deformability / Q000187:drug effects; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000378:metabolism; D004912:Erythrocytes / Q000187:drug effects* / Q000648:ultrastructure; D005954:Glucosephosphate Dehydrogenase / Q000097:blood; D005978:Glutathione / Q000097:blood; D007501:Iron / Q000097:blood; D050356:Lipid Metabolism; D008297:Male; D008314:Malonates / Q000494:pharmacology*; D008708:Methemoglobinemia / Q000139:chemically induced; D008855:Microscopy, Electron, Scanning; D051381:Rats
D008314:Malonates; D002784:Cholesterol; D007501:Iron; D005954:Glucosephosphate Dehydrogenase; D005978:Glutathione; C024808:diisopropyl 1,3-dithiol-2-ylidenemalonate