Abstract
BackgroundAcetaminophen (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.MethodsTwo 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.ResultsAlanine 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-γ, p62, and NRF2 were high in mice in the FF-A group.ConclusionsOur 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.
Highlights
Acetaminophen (APAP) is a readily available and safe painkiller
Mice in the fast food (FF)-S group had higher Alanine aminotransferase (ALT) level compared with the counterparts in the normal chow (NC)-S group (199.0 ± 39.0 vs. 63.8 ± 7.4 IU/L, p 0.017; Fig. 1B)
Non-alcoholic fatty liver disease (NAFLD) activity score that integrated the findings of histological analysis was significantly different between mice in the FF diet with saline injection (FF-S) and NC diet with saline injection (NC-S) groups (p < 0.001; Table 2)
Summary
Acetaminophen (APAP) is a readily available and safe painkiller. its overdose is the most common cause of acute liver injury (ALI). Non-alcoholic fatty liver disease (NAFLD), the major cause of chronic liver disease, is considered an important predictor of APAP-induced ALI, the exact mechanism controversial. Acetaminophen (APAP) is a readily available and commonly used antipyretic and analgesic drug worldwide [1,2,3]. It is safe when administered within its therapeutic dose; its overdose is the most common (50%) cause of acute liver failure in the US and other Western countries [2, 3]. Non-alcoholic fatty liver disease (NAFLD) is considered as a risk factor for APAP-induced ALI [7]. Non-alcoholic steatohepatitis (NASH), severe form of NAFLD, accompanies with oxidative stress, which were considered to lead severe APAP-induced ALI
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
