期刊
CHEMICO-BIOLOGICAL INTERACTIONS
卷 142, 期 1-2, 页码 57-71出版社
ELSEVIER SCI IRELAND LTD
DOI: 10.1016/S0009-2797(02)00054-6
关键词
adenosine triphosphate; hepatocytes; troglitazone
We report here our studies on troglitazone and rosiglitazone cytotoxicity in human hepatocytes isolated from multiple donors to investigate factors responsible for individual differences in sensitivity to the known hepatotoxicity of these antidiabetic drugs. Using cellular adenosine triphosphate (ATP) content as an endpoint, cytotoxicity of both drugs was evaluated in cryopreserved human hepatocytes from 37 donors. We confirmed reports of others that troglitazone was cytotoxic to human hepatocytes using cellular ATP content as an endpoint. In addition, we found that rosiglitazone, although less toxic in the study population, was cytotoxic to hepatocytes in some donors (EC50 < 100 muM). ATP content, 3-[4,5-dimethylthiazol-2-yl]-2.5-diphenyltetrazolium bromide (MTT) metabolism, depletion of intracellular glutathione. Alamar Blue metabolism, and neutral red uptake were used as endpoints in a single donor study using freshly isolated human hepatocytes. Troglitazone appeared to be more toxic than rosiglitazone by all endpoints. From the demographic data provided to us for each donor, we were able to establish no direct correlation between cytotoxicity (expressed as EC50 values) and age, sex, smoking status, or alcohol consumption. We conclude that troglitazone and rosiglitazone are differentially toxic to human hepatocytes, and that toxicity may be independent of age, sex, tobacco use, and alcohol use. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据