اشرفی حافظ, اصغر ، جمالی, ژاله ، خضری, صالح ، سلیمی, احمد (1400) تیموکینون باعث کاهش آسیب میتوکندری و مرگ کاردیومیوسیت های ناشی از کلوزاپین می شود. Naunyn-Schmiedeberg's Archives of Pharmacology ــ 394 (8). ص.ص.1675-1684. شاپا 0028-1298
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آدرس اینترنتی رسمی : https://www.springer.com/journal/210
عنوان انگليسی
Thymoquinone reduces mitochondrial damage and death of cardiomyocytes induced by clozapine
خلاصه انگلیسی
The generation of a reactive nitrenium ion by microsomal/mitochondrial cytochrome P450 (CYPs) from clozapine (CLZ) has been suggested as the main cause of cardiotoxicity by this drug. Previous studies indicated that thymoquinone (TQ) as an active constituent of Nigella sativa has pharmacological effects such as antioxidant, reactive oxygen species (ROS) scavenger, and inhibitory effect on CYPs enzymes. Therefore, we hypothesized that TQ with these pharmacological effects can reduce CLZ-induced toxicity in isolated cardiomyocytes and mitochondria. Rat left ventricular cardiomyocytes and mitochondria were isolated by collagenase perfusion and differential centrifugation respectively. Then, isolated cardiomyocytes and mitochondria were pretreated with different concentrations of TQ (1, 5, and 10 μmol/l) for 30 min and then followed by exposure to CLZ (50 μmol/l) for 6 h. After 6 h of incubation, using biochemical evaluations and flow cytometric analysis, the parameters of cellular toxicity including cytotoxicity, the level of oxidized/reduced glutathione (GSH/GSSG), malondialdehyde (MDA), reactive oxygen species (ROS) formation, lysosomal membrane integrity, mitochondria membrane potential (ΔΨm) collapse, and mitochondrial toxicity including succinate dehydrogenase (SDH) activity and mitochondrial swelling were analyzed. We observed a significant toxicity in isolated cardiomyocytes and mitochondria after exposure with CLZ which was related to ROS formation, oxidative stress, GSH depletion, lysosomal and mitochondrial damages, and mitochondrial dysfunction and swelling, while TQ pretreatment reverted the above toxic effect of CLZ on isolated cardiomyocytes and mitochondria. Our results indicate that TQ prevents and reverses CLZ-induced cytotoxicity and mitochondrial damages in isolated cardiomyocytes and mitochondria, providing an experimental basis for clinical treatment on CLZ-induced cardiotoxicity.
نوع سند : | مقاله |
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زبان سند : | انگلیسی |
نویسنده اول : | اصغر اشرفی حافظ |
نویسنده : | ژاله جمالی |
نویسنده : | صالح خضری |
نویسنده مسئول : | احمد سلیمی |
ضریب تاثیر و نمایه مجلات: | IF: 3 Indexed in:ISI, PubMed/Medline, Scopus, Embase |
کلیدواژه ها (فارسی): | پیشگیری؛ تیموکینون سیتوکروم P450؛ کاردیومیوپاتی ؛ میوکاردیت |
کلیدواژه ها (انگلیسی): | Prevention; Thymoquinone; Cytochrome P450; Cardiomyopathy; Myocarditis |
موضوعات : | QV فارماکولوژی > QV 600 سم شناسی QV فارماکولوژی |
بخش های دانشگاهی : | دانشکده داروسازی > بخش سم شناسی |
کد شناسایی : | 14452 |
ارائه شده توسط : | دکتر احمد سلیمی |
ارائه شده در تاریخ : | 31 خرداد 1400 11:24 |
آخرین تغییر : | 25 فروردین 1401 09:28 |
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