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 14weeks, 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±7.4IU/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±185.1IU/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-γ, 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-γ.
| Original language | English |
|---|---|
| Article number | 124 |
| Journal | BMC Gastroenterology |
| Volume | 17 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2017 Nov 28 |
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Keywords
- Acetaminophen
- Drug-induced liver injury
- Non-alcoholic fatty liver disease
- Peroxisome proliferator-activated receptor gamma
ASJC Scopus subject areas
- Gastroenterology
Cite this
Fast food diet-induced non-alcoholic fatty liver disease exerts early protective effect against acetaminophen intoxication in mice. / Kim, Tae Hyung; Choi, Dahee; Kim, Joo Young; Lee, Jeong Hyeon; Koo, Seung-Hoi.
In: BMC Gastroenterology, Vol. 17, No. 1, 124, 28.11.2017.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Fast food diet-induced non-alcoholic fatty liver disease exerts early protective effect against acetaminophen intoxication in mice
AU - Kim, Tae Hyung
AU - Choi, Dahee
AU - Kim, Joo Young
AU - Lee, Jeong Hyeon
AU - Koo, Seung-Hoi
PY - 2017/11/28
Y1 - 2017/11/28
N2 - 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 14weeks, 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±7.4IU/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±185.1IU/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-γ, 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-γ.
AB - 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 14weeks, 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±7.4IU/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±185.1IU/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-γ, 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-γ.
KW - Acetaminophen
KW - Drug-induced liver injury
KW - Non-alcoholic fatty liver disease
KW - Peroxisome proliferator-activated receptor gamma
UR - http://www.scopus.com/inward/record.url?scp=85035115764&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85035115764&partnerID=8YFLogxK
U2 - 10.1186/s12876-017-0680-z
DO - 10.1186/s12876-017-0680-z
M3 - Article
C2 - 29179698
AN - SCOPUS:85035115764
VL - 17
JO - BMC Gastroenterology
JF - BMC Gastroenterology
SN - 1471-230X
IS - 1
M1 - 124
ER -