| RRC ID |
39944
|
| Author |
Yamamoto Y, Nakajima M, Yamazaki H, Yokoi T.
|
| Title |
Cytotoxicity and apoptosis produced by troglitazone in human hepatoma cells.
|
| Journal |
Life Sci
|
| Abstract |
Troglitazone is an antidiabetic agent that increases the insulin sensitivity of target tissues in non-insulin-dependent diabetes mellitus. It has been reported that troglitazone causes severe hepatic injury in certain individuals. In the present study, the mechanism for the hepatic injury by troglitazone was investigated with human hepatoma cell lines. HepG2 cells were incubated with troglitazone, its metabolites M-1 (sulfate), M-2 (gulucronide), M-3 (quinone), and other thiazolidinediones (pioglitazone and rosiglitazone). Troglitazone exhibited time- and concentration-dependent cytotoxicity and M-3 also exhibited weak cytotoxicity. Troglitazone induced apoptotic cell death characterized by internucleosomal DNA fragmentation and nuclear condensation. As other thiazolidinediones, pioglitazone and rosiglitazone, did not induce cell death and apoptosis in the present study, the affinity to PPARgamma may not affect the induction of apoptosis by troglitazone. These results suggest that troglitazone induces apoptotic hepatocyte death which it may be one of the factors of liver injury in humans.
|
| Volume |
70(4)
|
| Pages |
471-82
|
| Published |
2001-12-14
|
| DOI |
10.1016/s0024-3205(01)01432-1
|
| PII |
S0024-3205(01)01432-1
|
| PMID |
11798015
|
| MeSH |
Apoptosis / drug effects*
Carcinoma, Hepatocellular
Cell Survival / drug effects
Chromans / metabolism
Chromans / toxicity*
DNA Fragmentation
Dose-Response Relationship, Drug
Humans
Hypoglycemic Agents / metabolism
Hypoglycemic Agents / toxicity*
Pioglitazone
Rosiglitazone
Tetrazolium Salts / metabolism
Thiazoles / metabolism
Thiazoles / toxicity*
Thiazolidinediones*
Troglitazone
Tumor Cells, Cultured / drug effects
Tumor Cells, Cultured / metabolism
Tumor Cells, Cultured / pathology
|
| IF |
3.647
|
| Times Cited |
74
|
|
WOS Category
|
PHARMACOLOGY & PHARMACY
MEDICINE, RESEARCH & EXPERIMENTAL
|
| Resource |
| Human and Animal Cells |
HuH-7(RCB1366) |
