Nagayama S, Yokoi T, Kawaguchi Y, Kamataki T
Division of Drug Metabolism, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
J Toxicol Sci. 1994 Aug;19(3):155-61. doi: 10.2131/jts.19.3_155.
The occurrence of an autoantibody to protein disulfide isomerase (PDI) in rats after administration of various hepatotoxic drugs was investigated by immunoblotting and radioimmunoassay. An anti-PDI autoantibody was detected with high frequency in rats treated with D-galactosamine, acetaminophen with diethylmaleate, and carbon tetrachloride with diethylmaleate. The antibody-positive rate was relatively low in the groups of rats given carbon tetrachloride, acetaminophen or DL-ethionine alone. The anti-PDI antibody was not detected in rats treated with diethylmaleate alone. Although the mechanism of the production of the anti-PDI autoantibody is unclear, the occurrence of anti-PDI antibody correlated with high serum GPT activities. It is suggested that the autoantibody plays an important role in the development and persistence of drug-induced hepatitis.
通过免疫印迹法和放射免疫测定法,研究了各种肝毒性药物给药后大鼠体内蛋白二硫键异构酶(PDI)自身抗体的产生情况。在用D-半乳糖胺、对乙酰氨基酚与马来酸二乙酯、四氯化碳与马来酸二乙酯处理的大鼠中,高频检测到抗PDI自身抗体。在单独给予四氯化碳、对乙酰氨基酚或DL-乙硫氨酸的大鼠组中,抗体阳性率相对较低。在仅用马来酸二乙酯处理的大鼠中未检测到抗PDI抗体。虽然抗PDI自身抗体产生的机制尚不清楚,但抗PDI抗体的出现与高血清谷丙转氨酶活性相关。提示该自身抗体在药物性肝炎的发生和持续发展中起重要作用。