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- Title
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; Sun-Ok Song; Eun Seok Kang; Bong Soo Cha; Hyun Chul Lee; Byung-Wan Lee
- Abstract
Background. Pentoxifylline (PTX) anti-TNF properties are known to exert hepatoprotective effects in various liver injury models. The aimof 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 (1mM). Results. PTX attenuated MCD-diet-induced serumALT 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 bene?cial roles in the development of MCD-diet-induced steatohepatitis through partial suppression of TNF-a and ER stress.
- Subjects
PENTOXIFYLLINE; LIVER diseases; FATTY degeneration; METHIONINE; LABORATORY rats; THERAPEUTICS
- Publication
Experimental Diabetes Research, 2012, p1
- ISSN
1687-5214
- Publication type
Article
- DOI
10.1155/2012/762565