Antipsychotic drugs scavenge radiation-induced hydroxyl radicals and intracellular ROS formation, and protect apoptosis in human lymphoma U937 cells
| Autor: | Takashi Uehara, Hitoshi Abe, Masayuki Ikeda, Masayoshi Kurachi, Kyo Noguchi, Jun-ichi Saitoh, Hiroko Ito, Takashi Kondo, Michio Suzuki, Qing-Li Zhao |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Olanzapine Antioxidant Lymphoma medicine.drug_class medicine.medical_treatment Atypical antipsychotic Apoptosis Pharmacology Biochemistry 03 medical and health sciences medicine Humans Antipsychotic Clozapine 030102 biochemistry & molecular biology U937 cell Chemistry Hydroxyl Radical General Medicine U937 Cells 030104 developmental biology Reactive Oxygen Species Intracellular medicine.drug Antipsychotic Agents |
| Zdroj: | Free radical research. 53(3) |
| ISSN: | 1029-2470 |
| Popis: | Antioxidant activity has been reported for some atypical antipsychotic drugs; however, the detailed mechanism is not well known. Here, we investigated the effects of atypical antipsychotic drugs on •OH radical formation, intracellular reactive oxygen species (ROS), and apoptosis induced by ionising radiation. The reaction rate constants with •OH radicals were determined for five antipsychotic drugs as follows, in descending order: olanzapine, aripiprazole, clozapine, haloperidol, and risperidone. Experiments with aminophenyl fluorescein, a fluorescent dye, showed that olanzapine and clozapine could scavenge intracellular ROS. However, experiments with hydroxyphenyl fluorescein showed that only olanzapine inhibited ROS generation. X-irradiation-induced apoptosis in human lymphoma U937 cells was inhibited by clozapine at relatively low concentrations and by olanzapine at higher concentrations. Clozapine inhibited caspase-8 and caspase-3 activation and prevented loss of mitochondrial membrane potential. In contrast, olanzapine inhibited X-irradiation-induced p-JNK activation. Although the atypical antipsychotic drugs used here have relatively high reaction rate constants with •OH radicals in aqueous solutions, inhibition of intracellular ROS was not due to •OH radical scavenging. In addition, suppression of X-irradiation-induced apoptosis was not directly linked with intracellular ROS scavenging. When apoptosis signalling pathways were studied, clozapine-mediated inhibition of apoptosis was dependent on caspase-3 and caspase-8. In contrast, olanzapine inhibited apoptosis via down regulation of X-irradiation-induced p-JNK. These results suggested that both olanzapine and clozapine have antioxidative and antiapoptotic activities via distinct pathways, and provide useful information for better understanding of drug characteristics. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
| Nepřihlášeným uživatelům se plný text nezobrazuje | K zobrazení výsledku je třeba se přihlásit. |