کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6109600 1211209 2009 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Resolution of inflammation-related apoptotic processes by the synthetic tellurium compound, AS101 following liver injury
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی بیماری‌های گوارشی
پیش نمایش صفحه اول مقاله
Resolution of inflammation-related apoptotic processes by the synthetic tellurium compound, AS101 following liver injury
چکیده انگلیسی

Background/AimsFulminant hepatic failure is a dangerous condition, which occurs when large parts of the liver become damaged beyond repair, and the liver is no longer able to function. This syndrome is induced by inflammatory processes, resulting in acute liver failure. Recently, the organotellurium compound, trichloro(dioxoethylene-O,O′) tellurate (AS101), has been found by our group to be able to directly inhibit caspases, due to its Te(IV)-thiol chemistry. The aim of this study was to examine the potential of AS101 as an anti-inflammatory and anti-apoptotic compound in vitro and in vivo following liver injury.MethodsPropionibacterium acnes-primed LPS-induced liver injury was performed in Balb/c mice. ALT/AST, cytokines, caspase-1,-3 and-8 activities, and liver histology were assessed.ResultsAS101 inhibited TNFα or anti-FAS-induced apoptotic processes in hepatocytes in vitro. A P. acnes + LPS in vivo liver injury model revealed lower serum ALT and AST and reduced necrosis and apoptosis in AS101-treated mice. IL-18 and IL-1β reduced levels in AS101-treated mice were associated with caspase-1 activity inhibition. Our findings suggest IL-6, IL-17 and pSTAT3 as additional novel players in the pathogenicity of FHF. Inhibition of caspase-3, and-8 activities by AS101 treatment contributed to decreased hepatocyte death, resulting in increased survival.ConclusionsWe suggest that due to its interaction with key-target cysteine residues, AS101 mediates anti-inflammatory and anti-apoptotic effects in this FHF model, which may serve as a potent treatment for mitigation of hepatic damage.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Hepatology - Volume 51, Issue 3, September 2009, Pages 491-503
نویسندگان
, , , ,