کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5859940 1562633 2014 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Triptolide-induced oxidative stress involved with Nrf2 contribute to cardiomyocyte apoptosis through mitochondrial dependent pathways
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Triptolide-induced oxidative stress involved with Nrf2 contribute to cardiomyocyte apoptosis through mitochondrial dependent pathways
چکیده انگلیسی


- Triptolide (TP) has potential toxicity on heart.
- Cardiotoxicity of TP involves ROS-mediated mitochondria-dependent apoptosis pathway.
- Nrf2 pathway is an important mediator in TP-induced oxidative stress.
- Nrf2 may be a promising cardioprotective target against TP-induced cardiac injury.

Triptolide (TP), a major active ingredient extracted from the widely used Chinese herb Tripterygium wilfordii Hook f. (TWHF), has been demonstrated to possess various biological activities. However, the clinical applications of TP are limited by its narrow therapeutic window and severe toxicity. The current study aimed to investigate the roles of reactive oxygen species (ROS) and mitochondria in TP-induced cardiac injury. Male BALB/C mice were intravenously (i.v.) treated with a single dose of TP (1.2 mg/kg). After 24 h, TP induced the oxidative stress, mitochondrial dysfunction, apoptotic damage, and pathological changes of heart tissue. In vitro studies also indicated that the cytotoxic effects of TP involved the ROS-mediated mitochondria-dependent pathway in H9c2 cells. TP treatment increased the accumulation of ROS and subsequently triggered cell apoptosis by depolarizing the mitochondrial membrane potential (ΔΨm), reduced the ratio of Bax/Bcl-2, released cytochrome c and, ultimately, activated caspase-3. Nrf2, as well as its downstream antioxidants, were also suppressed by TP. Taken together, these results suggest that TP induces cardiotoxicity in vivo and in vitro via oxidative stress, which was associated with down regulated Nrf2 activation, and the mitochondria-mediated apoptotic signaling pathway.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology Letters - Volume 230, Issue 3, 4 November 2014, Pages 454-466
نویسندگان
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