Mitochondria and plasma membrane as targets of UVA-induced toxicity of neuroleptic drugs fluphenazine, perphenazine and thioridazine
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- 作者：Bastianon ; Chiara ; Zanoni ; Roberta ; Miolo ; Giorgia ; Caffieri ; Sergio ; Reddi ; Elena
- 关键词：D-MEM ; Dulbecco's modified Eagle's medium ; D-PBS ; Dulbecco's phosphate buffered saline ; FCS ; foetal calf serum ; FP ; fluphenazine ; LDH ; lactate dehydrogenase ; NAC ; N-acetylcysteine ; PP ; perphenazine ; SOD ; superoxide dismutase ; TR ; thioridazine ; Mito
- 刊名：International Journal of Biochemistry and Cell Biology
- 出版年：2005
- 出版时间：April, 2005
- 年：2005
- 卷：37
- 期：4
- 页码：901-908
- 全文大小：194 K
文摘
In order to gain insights into the mechanism of phototoxicity of the neuroleptic drugs fluphenazine, perphenazine and thioridazine in cultured cells, studies were performed with murine 3T3 fibroblasts, aimed at identifying some cellular targets responsible for photoinduced cell death and possible cytotoxic reactive species involved in the photosensitization process. 3T3 fibroblasts incubated with 5μM drugs and irradiated with UVA light (up to 8J/cm2) underwent cell death, the extent of which depended on light dose. Of the three drugs, fluphenazine exhibited the highest phototoxicity and 100 % cell death was achieved with a light dose of 5J/cm2. Superoxide dismutase and α-tocopherol exerted a dose-dependent protective effect against drug phototoxicity, whereas N-acetylcysteine failed to do so. These findings indicate that superoxide anion and other free radical intermediates, generated in lipophilic cellular environments, play a role in photoinduced toxicity. Phototreatment of drug-loaded cells induces release of the cytosolic enzyme lactate dehydrogenase and causes loss of activity of mitochondrial NADH dehydrogenase, indicating that plasma membrane and mitochondria are among the targets of the phototoxicity of these drugs.