The effects of acrylonitrile on hemoglobin and red cell metabolism

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Abstract
The effects of acrylonitrile (VCN) on Hb 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 was enzymic and nonenzymic. GSH depletion induced oxidation of most Hb 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 0.05 M, and at < 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, ATP pyruvate, lactate and oxidized glutathione occurred within 1 h. These changes returned to normal levels between 6-24 h. A strong correlation between the depletion of GSH in vivo and covalent binding [2,3-14C] VCN to Hb was observed. These in vivo and in vitro results suggested that chronic exposure to VCN may have led to methemoglobinemia and caused impaired delivery of O2 to various tissues.