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Experimental Diabetes Research
Volume 2012 (2012), Article ID 762565, 8 pages
http://dx.doi.org/10.1155/2012/762565
Research Article

Pentoxifylline Attenuates Methionine- and Choline-Deficient-Diet-Induced Steatohepatitis by Suppressing TNF-α Expression and Endoplasmic Reticulum Stress

1Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea
2College of Biomedical Sciences, CHA University, Seongnam 463-836, Republic of Korea
3Advanced Institutes of Convergence Technology (AICT), Seoul National University, Suwon 443-270, Republic of Korea

Received 7 June 2011; Revised 27 September 2011; Accepted 20 October 2011

Academic Editor: Lalit P. Singh

Copyright © 2012 Min Kyung Chae et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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, ), 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.