| 6668618 |
Farooqui MY, Ahmed AE: The effects of acrylonitrile on hemoglobin and red cell metabolism. . Regul Toxicol Pharmacol. 2007 Mar;47(2):171-83. Epub 2006 Oct 10.
The effects of acrylonitrile (VCN) on hemoglobin and red cell metabolism were studied in vitro and in vivo using male Sprague-Dawley rats. Reduced glutathione (GSH) was rapidly depleted by VCN. The reaction between VCN and GSH to form S-cyanoethyl glutathione is both enzymic and nonenzymic. GSH depletion induced oxidation of considerable amount of hemoglobin to methemoglobin. Incubation of nitrite-treated erythrocytes with VCN (2-10 mM) resulted in a significant decrease in methemoglobin reduction. VCN initiated hemolysis in vitro at a concentration of 0.05 M, and at concentrations lower than 0.05 M rendered erythrocytes susceptible to osmotic fragility even at higher concentration of NaCl. Following oral administration of VCN (80 mg/kg), significant perturbations of levels of red-cell GSH, 2,3-diphosphoglycerate, adenosine triphosphate, pyruvate, lactate, and oxidized glutathione occurred within 1 h. These changes returned to normal levels between 6 and 24 h. A strong correlation between the depletion of GSH in vivo and covalent binding [2,3-14C] VCN to hemoglobin was observed. These in vivo and in vitro results suggest that chronic exposure to VCN may lead to methemoglobinemia and consequently may cause impaired delivery of oxygen to various tissues. |
64(0,2,2,4) |