Biochemical Changes in Rat Erythrocytes Caused by Ethylene Oxide Exposure

Biochemical Changes in Rat Erythrocytes Caused by Ethylene OxideExposure. MORI, K., INOUE, N., FUJISHIRO, K., KIKUCHI, M., ANDCHIBA S. (1990). Fundam. Appl. Toxicol. 15, 441–447. WhenWistar male rats were exposed to ethylene oxide (EtO) at a concentrationof about 500 ppm, 6 hr a day, 3 days a week for 2, 6, or 13weeks, hematological examination showed macrocytic, normochromicanemia with a high reticulocyte count This result raised thepossibility that the hemolytic process was responsible for theanemia. Thus, the following possible causes of hemolysis wereinvestigated with erythrocytes obtained from control and EtO-exposedrats. (1) Metabolism in erythrocytes; (a) Hexose monophosphatecycle: The activity of glucose-6-phosphate dehydrogenase, 6-phosphogluconatedehydrogenase, or glutathione perox-idase was not affected,but the activity of glutathione reductase (GR) significantlydecreased and did not recover by the addition of flavin adeninedinucleotide. Reduced glutathione content also decreased andthe glutathione stability test was positive, (b) Embden-Meyerhofpathway: Adenosine triphosphate content did not decrease, (c)Lapoport-Luebering cycle: 2,3-Diphos-phoglycerate content wasnot affected. (2) Membrane alterations: Osmotic fragility wasnot affected and the activity of acetylcholine esterase in theghost membranes of the exposed group increased. (3) Hemoglobinstability: The heat test and the isopropanol test were negative.GR has an important function in maintaining the reducing powerin erythrocytes, and the decrease in the activity caused byEtO induced an alteration of the glutathione stability. Althoughthe mechanism of EtO-induced anemia could not be clearly explained,the inhibition of GR activity might be related to the anemia.