論文 - 詳細
| RRC ID | 42877 |
|---|---|
| 著者 | Sasaki A, Oshima Y, Fujimura A. |
| タイトル | An approach to elucidate potential mechanism of renal toxicity of arsenic trioxide. |
| ジャーナル | Exp Hematol |
| Abstract |
OBJECTIVE:To investigate arsenic trioxide's renal toxicity, we analyzed the gene-expression patterns of primary renal and human kidney cells (HEK293 cell line) following exposure to arsenic trioxide. Moreover, we examined a potential renal toxic mechanism(s) of arsenic trioxide by using a toxicity-related gene and investigated potential treatments to reduce the renal toxicity of arsenic trioxide. MATERIALS AND METHODS:Arsenic trioxide was exposed to primary renal and HEK293 cells, and the gene-expression analysis was conducted using DNA microarray. Then, reactive oxygen species inhibitors or alpha-lipoic acid were added to HEK293 cells exposed arsenic trioxide and cell viability was determined. RESULTS:Expression of HMOX1 mRNA increased in a time- and dose-dependent manner, and translation of heme oxygenase 1 protein was also induced. Arsenic trioxide-induced cytotoxicity was inhibited by reactive oxygen species inhibitors. Moreover, superoxide anion was detected in arsenic trioxide-treated HEK293 cells. alpha-Lipoic acid ameliorated arsenic trioxide-induced cytotoxicity and reduced superoxide anion production in HEK293 cells, whereas it had no effect in promyelocytic leukemia cells (HL-60 cells and NB4 cells) and myeloma cells (KMS12BM cells and U266 cells). CONCLUSIONS:Arsenic trioxide-induced renal toxicity is strongly associated with the increased expression of HMOX1, and the cytotoxic mechanisms of arsenic trioxide involves reactive oxygen species production as well as another pathway. These preliminary results suggest that alpha-lipoic acid may be a suitable agent for prevention or treatment of arsenic trioxide-induced renal toxicity. |
| 巻・号 | 35(2) |
| ページ | 252-62 |
| 公開日 | 2007-2-1 |
| DOI | 10.1016/j.exphem.2006.10.004 |
| PII | S0301-472X(06)00655-2 |
| PMID | 17258074 |
| MeSH | 1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt / pharmacology Arsenic Trioxide Arsenicals / antagonists & inhibitors Catalase / pharmacology Catecholamines / pharmacology Cell Death / drug effects Cell Survival / drug effects Cells, Cultured Cluster Analysis Dose-Response Relationship, Drug Gene Expression Profiling Gene Expression Regulation / drug effects* Gene Expression Regulation / genetics HL-60 Cells Heme Oxygenase-1 / drug effects* Heme Oxygenase-1 / genetics Heme Oxygenase-1 / metabolism Humans Imidazolines / pharmacology Kidney Cortex / cytology Kidney Cortex / drug effects* Oligonucleotide Array Sequence Analysis / methods Oxides / antagonists & inhibitors Oxides / toxicity* RNA, Messenger / drug effects RNA, Messenger / genetics RNA, Messenger / metabolism Reactive Oxygen Species / antagonists & inhibitors Reactive Oxygen Species / metabolism Reverse Transcriptase Polymerase Chain Reaction / methods Superoxides / antagonists & inhibitors Superoxides / metabolism Thioctic Acid / pharmacology Time Factors |
| IF | 2.82 |
| 引用数 | 33 |
| WOS 分野 | MEDICINE, RESEARCH & EXPERIMENTAL HEMATOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | |