کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
9034572 1562442 2005 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The effect of ursodeoxycholic acid on glycochenodeoxycholic acid-induced apoptosis in rat hepatocytes
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
The effect of ursodeoxycholic acid on glycochenodeoxycholic acid-induced apoptosis in rat hepatocytes
چکیده انگلیسی
Ursodeoxycholic acid (UDCA) has been widely used for treating cholestatic liver diseases. However, in a recent review of clinical trial articles, its therapeutic benefits were not proven. Therefore, we investigated whether UDCA prevents or potentiates glycochenodeoxycholic acid (GCDCA)-induced apoptosis in isolated rat hepatocytes. Hepatocellular cytotoxicity was assessed by lactate dehydrogenase (LDH) release, and apoptosis evaluated by DNA fragmentation, caspase activities, release of cytochrome C from mitochondria, and mitochondrial membrane potential change (Δψ). When hepatocytes were co-incubated with GCDCA and UDCA for a short time (2-6 h), GCDCA-induced LDH release was significantly reduced, while prolonged co-incubation (12-20 h) increased it. Similarly, the same co-incubation for a short time resulted in the inhibition of caspase activities and cytochrome C release, while prolonged incubation enhanced them compared with the incubation with GCDCA alone. Furthermore, UDCA significantly promoted the GCDCA-induced Δψ decline after 4 h of incubation. These results demonstrated that UDCA reduced GCDCA-induced apoptosis in short incubation, but potentiated it in prolonged incubation. Based on these, we propose a hypothesis that induction of Δψ decrease from earlier stage of incubation may be responsible for the aggravation of GCDCA-induced apoptosis in long-term exposure, and would like to raise caution about clinical long-term use of UDCA.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology - Volume 214, Issues 1–2, 15 October 2005, Pages 77-86
نویسندگان
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