Ghanayem B I, Maronpot R R, Matthews H B
National Institute of Environmental Health Sciences, Research Triangle Park, NC.
Toxicol Lett. 1991 Feb;55(2):215-21. doi: 10.1016/0378-4274(91)90136-t.
Acute administration of a single dose of ethyl acrylate (EA) to F344 rats by gavage caused time- and dose-dependent forestomach edema. Evidence from our laboratory and others suggested that EA is hydrolyzed to acrylic acid (AA) and ethanol both in vivo and in vitro. The major metabolites detected in teh urine of rats treated with EA were derivatives of the glutathione conjugates of EA and AA. The current work was undertaken to investigate the effects of sulfhydryl-depleting agents (diethylmaleate and fasting) and sulfhydryl-containing agents (cysteine and cysteamine) on EA-induced forestomach edema. Results presented in this report revealed that pretreatment of rats with sulfhydryl-containing chemicals such as cysteine or cysteamine has potentiated EA-induced forestomach edema. In contrast, depletion of indigenous sulfhydryls by fasting of rats or pretreatment with diethylmaleate (DEM) protected against EA-induced forestomach edema. Furthermore, repetitive daily administration of EA by gavage induced mucosal forestomach hyperplasia. Co-administration of cysteamine and EA resulted in a significant enhancement of the severity of EA-induced forestomach mucosal hyperplasia. In conclusion, current data suggest that modulation of indigenous sulfhydryls play a role in EA-induced forestomach toxicity; however, the exact mechanism underlying this role remains to be characterized.
通过灌胃法给F344大鼠一次性急性给予单剂量丙烯酸乙酯（EA）会导致前胃水肿呈现时间和剂量依赖性。我们实验室及其他机构的证据表明，EA在体内和体外均会水解为丙烯酸（AA）和乙醇。在用EA处理的大鼠尿液中检测到的主要代谢物是EA和AA的谷胱甘肽缀合物衍生物。开展当前这项研究是为了调查巯基耗竭剂（马来酸二乙酯和禁食）和含巯基剂（半胱氨酸和半胱胺）对EA诱导的前胃水肿的影响。本报告中呈现的结果显示，用含巯基化学物质如半胱氨酸或半胱胺对大鼠进行预处理会增强EA诱导的前胃水肿。相反，通过大鼠禁食或用马来酸二乙酯（DEM）预处理来耗尽内源性巯基可预防EA诱导的前胃水肿。此外，通过灌胃法每日重复给予EA会诱导前胃黏膜增生。半胱胺与EA共同给药会显著增强EA诱导的前胃黏膜增生的严重程度。总之，当前数据表明内源性巯基的调节在EA诱导的前胃毒性中起作用；然而，这一作用背后的确切机制仍有待阐明。
