Costa L G, Deng H, Calleman C J, Bergmark E
University of Washington, Department of Environmental Health, Seattle 98195, USA.
Toxicology. 1995 Apr 12;98(1-3):151-61. doi: 10.1016/0300-483x(94)02986-5.
Acrylamide is an important chemical used in the synthesis of polyacrylamides, which have a wide variety of industrial applications. The principal toxic effect of acrylamide, both in animals and in humans, is neurotoxicity. Peripheral nervous system effects are most prominent, but central nervous system effects have also been reported. Acrylamide is metabolized to the epoxide glycidamide, whose adducts to hemoglobin and to DNA have been identified in animals and humans. This metabolite may be involved in the reproductive and carcinogenic effects of acrylamide. In the present study we investigated whether glycidamide would exert neurotoxic effects similar to those caused by its parent compound. Male rats were injected i.p. with acrylamide (25 or 50 mg/kg) or glycidamide (50 or 100 mg/kg) daily for 8 days. Reduced weight gain was evident in animals exposed to glycidamide or to the higher dose of acrylamide. Both compounds induced lethargy and ataxia, but the posture of glycidamide-treated rats differed from that of animals treated with acrylamide. At the high doses, both compounds significantly affected rats' behavior in the rotarod test; on the other hand, only acrylamide was effective in the hindlimb splay test. Acrylamide inhibited activity of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in sciatic and tibial nerves, as well as in brain. Glycidamide inhibited GAPDH activity only in brain and activity of creatine kinase in both peripheral and central tissues. Acrylamide also caused profound urinary retention and distended bladders, while the effects of glycidamide were minimal. Morphological abnormalities were seen in sciatic nerves and dorsal root ganglion cells of rats treated with acrylamide (50 mg/kg x 12), but not in rats exposed to glycidamide (100 mg/kg x 11). These results indicate that the toxicities of acrylamide and glycidamide differ and suggest that acrylamide itself may be primarily responsible for its peripheral neurotoxicity.
丙烯酰胺是一种用于合成聚丙烯酰胺的重要化学物质，聚丙烯酰胺有广泛的工业应用。丙烯酰胺对动物和人类的主要毒性作用是神经毒性。外周神经系统的影响最为显著，但中枢神经系统的影响也有报道。丙烯酰胺代谢为环氧化物缩水甘油酰胺，其与血红蛋白和DNA的加合物已在动物和人类中得到鉴定。这种代谢产物可能与丙烯酰胺的生殖和致癌作用有关。在本研究中，我们调查了缩水甘油酰胺是否会产生与其母体化合物相似的神经毒性作用。雄性大鼠每天腹腔注射丙烯酰胺（25或50mg/kg）或缩水甘油酰胺（50或100mg/kg），持续8天。暴露于缩水甘油酰胺或较高剂量丙烯酰胺的动物体重增加明显减少。两种化合物均诱导嗜睡和共济失调，但缩水甘油酰胺处理的大鼠的姿势与丙烯酰胺处理的动物不同。在高剂量下，两种化合物均显著影响大鼠在转棒试验中的行为；另一方面，只有丙烯酰胺在下肢外展试验中有效。丙烯酰胺抑制坐骨神经、胫神经以及脑中甘油醛-3-磷酸脱氢酶（GAPDH）的活性。缩水甘油酰胺仅抑制脑中GAPDH的活性以及外周和中枢组织中肌酸激酶的活性。丙烯酰胺还导致严重的尿潴留和膀胱扩张，而缩水甘油酰胺的影响最小。在用丙烯酰胺（50mg/kg×12）处理的大鼠的坐骨神经和背根神经节细胞中观察到形态学异常，但在暴露于缩水甘油酰胺（100mg/kg×11）的大鼠中未观察到。这些结果表明丙烯酰胺和缩水甘油酰胺的毒性不同，并表明丙烯酰胺本身可能是其外周神经毒性的主要原因。
