Coffee prevents IQ-induced liver damage by regulating oxidative stress, inflammation, endoplasmic reticulum stress, autophagy, apoptosis, and the MAPK/NF-κB signaling pathway in zebrafish

2-Amino-3-methylimidazole[4,5-f]quinoline (IQ), one of heterocyclic amines (HCAs) produced in proteinaceous foods upon heating, is recognized as a carcinogen. Previous studies have confirmed that IQ intake can cause liver damage in zebrafish. In the current study, we revealed the protective effects of coffee against IQ-induced liver damage. We exposed one-month-old wild-type zebrafish to IQ (80 ng/mL) and coffee at 50 mg/L, 100 mg/L, and 300 mg/L for 35 days. Markers of oxidative stress, inflammation, endoplasmic reticulum stress (ERS), autophagy, and apoptosis in the liver were assessed to explore the potential mechanisms of the protective effects. The results showed that coffee effectively improved IQ-induced liver damage by reducing ALT, AST, TC, TG, and LDL-C levels, increasing HDL-C level, and restoring hepatic morphology. Moreover, coffee showed an antioxidative effect by increasing GSH, GSH-Px, GST, CAT, and SOD levels and attenuating ROS and MDA contents. Additionally, coffee reduced the NO, iNOS, TNF-α, IL-6, IL-1β, and IL-12 expression levels, presenting an anti-inflammatory effect. Furthermore, coffee protected against ERS, autophagy dysfunction, and apoptosis by decreasing the GRP78, CHOP, and p62 while increasing the Atg5-Atg12, Beclin1, LC3-II, and Bcl-2 expression levels. TUNEL results showed that coffee rescued IQ-induced hepatocyte apoptosis. In addition, coffee interrupted the MAPK/NF-κB signaling pathway by suppressing the phosphorylation expressions of JNK, ERK, p38, p65, and IκB. These findings indicated that coffee prevents IQ-induced liver damage with antioxidative, anti-inflammatory, anti-ERS, anti-apoptotic, and pro-autophagic effects, thus to serve as a functional beverage with potential health benefits.