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Pentoxifylline attenuates methionine- and choline-deficient-diet-induced steatohepatitis by suppressing TNF-α expression and endoplasmic reticulum stress.

Authors
 Min Kyung Chae ; Sang Gyu Park ; Byung-Wan Lee ; Hyun Chul Lee ; Bong Soo Cha ; Eun Seok Kang ; Sun-Ok Song 
Citation
 Experimental Diabetes Research, Vol.2012 : 762565, 2012 
Journal Title
 Experimental Diabetes Research 
ISSN
 1687-5214 
Issue Date
2012
Abstract
BACKGROUND: Pentoxifylline (PTX) anti-TNF properties are known to exert hepatoprotective effects in various liver injury models. The aim of this study was to investigate whether PTX has beneficial roles in the development of methionine- and choline-deficient-(MCD-) diet-induced NAFLD SD rats in vivo and TNF-α-induced Hep3B cells in vitro. METHODS: SD Rats were classified according to diet (chow or MCD diet) and treatment (normal saline or PTX injection) over a period of 4 weeks: group I (chow + saline, n = 4), group II (chow + PTX), group III (MCD + saline), and group IV (MCD + PTX). Hep3B cells were treated with 100 ng/ml TNF-α (24 h) in the absence or presence of PTX (1 mM). RESULTS: PTX attenuated MCD-diet-induced serum ALT levels and hepatic steatosis. In real-time PCR and western blotting analysis, PTX decreased MCD-diet-induced TNF-alpha mRNA expression and proapoptotic unfolded protein response by ER stress (GRP78, p-eIF2, ATF4, IRE1α, CHOP, and p-JNK activation) in vivo. PTX (1 mM) reduced TNF-α-induced activation of GRP78, p-eIF2, ATF4, IRE1α, and CHOP in vitro. CONCLUSION: PTX has beneficial roles in the development of MCD-diet-induced steatohepatitis through partial suppression of TNF-α and ER stress.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/90278
DOI
10.1155/2012/762565
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Yonsei Biomedical Research Center
1. 연구논문 > 1. College of Medicine > Dept. of Internal Medicine
Yonsei Authors
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