Farooqui M Y, Ahmed A E
J Toxicol Environ Health. 1983 Oct-Dec;12(4-6):695-707. doi: 10.1080/15287398309530461.
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.
利用雄性斯普拉格-道利大鼠，在体外和体内研究了丙烯腈（VCN）对血红蛋白和红细胞代谢的影响。VCN可迅速消耗还原型谷胱甘肽（GSH）。VCN与GSH反应形成S-氰基乙基谷胱甘肽的过程既有酶促反应也有非酶促反应。GSH的消耗导致大量血红蛋白氧化为高铁血红蛋白。用VCN（2 - 10 mM）处理经亚硝酸盐处理的红细胞后，高铁血红蛋白还原显著减少。VCN在体外浓度为0.05 M时引发溶血，在低于0.05 M的浓度下，即使在较高浓度的氯化钠存在下，也会使红细胞对渗透脆性敏感。口服VCN（80 mg/kg）后，红细胞内GSH、2,3 - 二磷酸甘油酸、三磷酸腺苷、丙酮酸、乳酸和氧化型谷胱甘肽水平在1小时内出现显著波动。这些变化在6至24小时内恢复到正常水平。观察到体内GSH的消耗与[2,3 - 14C]VCN与血红蛋白的共价结合之间存在很强的相关性。这些体内和体外研究结果表明，长期接触VCN可能导致高铁血红蛋白血症，进而可能导致向各种组织输送氧气受损。
