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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  ;  Sun-Ok Song  ;  Eun Seok Kang  ;  Bong Soo Cha  ;  Hyun Chul Lee  ;  Byung-Wan Lee 
Citation
 Experimental Diabetes Research, Vol.2012 : 762565, 2012 
Journal Title
 Experimental Diabetes Research 
ISSN
 1687-5214 
Issue Date
2012
MeSH
Alanine Transaminase/blood ; Animals ; Cell Line ; Choline Deficiency/complications* ; Diet ; Endoplasmic Reticulum Stress/drug effects* ; Fatty Liver/drug therapy* ; Fatty Liver/etiology ; Male ; Methionine/deficiency* ; Non-alcoholic Fatty Liver Disease ; Pentoxifylline/therapeutic use* ; Phosphodiesterase Inhibitors/therapeutic use* ; Rats ; Rats, Sprague-Dawley ; Signal Transduction/drug effects ; Tumor Necrosis Factor-alpha/antagonists & inhibitors* ; Tumor Necrosis Factor-alpha/biosynthesis ; Tumor Necrosis Factor-alpha/pharmacology ; Unfolded Protein Response/drug effects
Keywords
Alanine Transaminase/blood ; Animals ; Cell Line ; Choline Deficiency/complications* ; Diet ; Endoplasmic Reticulum Stress/drug effects* ; Fatty Liver/drug therapy* ; Fatty Liver/etiology ; Male ; Methionine/deficiency* ; Non-alcoholic Fatty Liver Disease ; Pentoxifylline/therapeutic use* ; Phosphodiesterase Inhibitors/therapeutic use* ; Rats ; Rats, Sprague-Dawley ; Signal Transduction/drug effects ; Tumor Necrosis Factor-alpha/antagonists & inhibitors* ; Tumor Necrosis Factor-alpha/biosynthesis ; Tumor Necrosis Factor-alpha/pharmacology ; Unfolded Protein Response/drug effects
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.
Files in This Item:
T201203070.pdf Download
DOI
22319522
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kang, Eun Seok(강은석) ORCID logo https://orcid.org/0000-0002-0364-4675
Song, Sun Ok(송선옥)
Lee, Byung Wan(이병완) ORCID logo https://orcid.org/0000-0002-9899-4992
Lee, Hyun Chul(이현철)
Cha, Bong Soo(차봉수) ORCID logo https://orcid.org/0000-0003-0542-2854
Chae, Min Kyung(채민경)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/90278
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