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Cited 9 time in webofscience Cited 12 time in scopus
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Fast food diet-induced non-alcoholic fatty liver disease exerts early protective effect against acetaminophen intoxication in mice

Authors
Kim, Tae HyungChoi, DaheeKim, Joo YoungLee, Jeong HyeonKoo, Seung-Hoi
Issue Date
28-Nov-2017
Publisher
BMC
Keywords
Acetaminophen; Non-alcoholic fatty liver disease; Drug-induced liver injury; Peroxisome proliferator-activated receptor gamma
Citation
BMC GASTROENTEROLOGY, v.17
Indexed
SCIE
SCOPUS
Journal Title
BMC GASTROENTEROLOGY
Volume
17
URI
https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/4427
DOI
10.1186/s12876-017-0680-z
ISSN
1471-230X
Abstract
Background: Acetaminophen (APAP) is a readily available and safe painkiller. However, its overdose is the most common cause of acute liver injury (ALI). Many predisposing factors contribute to susceptibility to APAP-induced ALI. Non-alcoholic fatty liver disease (NAFLD), the major cause of chronic liver disease, is considered an important predictor of APAP-induced ALI, although the exact mechanism controversial. In this study, we aimed to elucidate the effects of NAFLD on APAP-induced ALI. Methods: Two groups of mice, normal chow (NC) diet-fed and fast food (FF) diet-fed mice for 14 weeks, were further divided into two subgroups: intraperitoneally injected with either saline (NC-S and FF-S groups) or APAP (NC-A and FF-A groups). Biochemical tests, histological analysis, quantitative PCR, and western blotting were conducted. Results: Alanine aminotransferase (ALT) level (199.0 +/- 39.0 vs. 63.8 +/- 7.4 IU/L, p < 0.05) and NAFLD activity score (0 vs. 4.5 +/- 0.22) were significantly higher in mice in FF-S group than those in NC-S group. ALI features such as ALT level (8447.8 +/- 1185.3 vs. 836.6 +/- 185.1 IU/L, p < 0.001) and centrizonal necrosis were prominent and mRNA levels of Trib3 (RR, 1.81) was high in mice in the NC-A group. Levels of CYP2E1 and anti-inflammatory molecules such as PPAR-gamma, p62, and NRF2 were high in mice in the FF-A group. Conclusions: Our results showed that while the FF diet clearly induced non-alcoholic steatohepatitis and metabolic syndrome, NAFLD also attenuates APAP-induced ALI by inducing anti-inflammatory molecules such as PPAR-gamma.
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Kim, Tae Hyung
안산병원 (Department of Gastroenterology and Hepatology, Ansan Hospital)
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