Triiodothyronine alleviates alcoholic liver disease injury through the negative regulation of the NLRP3 signaling pathway

The aim of the present study was to investigate the effect and mechanism of triiodothyronine (T3) on alcoholic liver disease (ALD)-induced injuries in mice. A total of 40 male C57/BL6 mice were randomly divided into the Control, ALD, ALD+T3 and ALD+T3+AMP-activated protein kinase inhibitor (CC) groups. Mice were administered alcohol (4 g/kg/day) intragastrically for 4 weeks except for Control group. Mice in the ALD+T3 group were given T3 (0.1 mg/kg/day) while mice in ALD+T3+CC group were given T3 (0.1 mg/kg/day) and CC (10 mg/kg/day) for 1 week. Control and ALD groups were treated with saline. Liver tissue and blood samples were obtained for testing. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBIL) levels were determined and morphological changes in the liver tissues were observed under the optical microscope. Inflammatory factors, including IL-1β and transforming growth factor (TGF)-β/1, α-smooth muscle actin (SMA) and protein levels of nucleotide-binding oligomerization domain, leucine rich repeat containing family, pyrin domain containing 3 (NLRP3), caspase-1 and pro-IL-1β were measured. Serum ALT, AST and TBIL levels in the ALD+T3 group were significantly reduced compared with the ALD group, while they were significantly increased in the ALD+T3+CC group (P<0.05). The number of hepatic lobules in the ALD+T3 group was significantly reduced compared with the ALD group, whereas the number in the ALD+T3+CC group was significantly increased (P<0.05). IL-1β and TGF-β1 levels in the ALD+T3 group were significantly decreased compared with the ALD group; however, levels in the ALD+T3+CC group were significantly increased compared with the ALD+T3 group (P<0.05). In addition, it was revealed that the expression of α-SMA mRNA and protein in the ALD+T3 group was significantly decreased compared with the ALD group, whereas it was significantly increased in the ALD+T3+CC group compared with the ALD+T3 group. Expression of NLRP3, caspase-1, IL-1β and TGF-β1 in the ALD+T3 group was significantly decreased compared with the ALD group, while expression was significantly increased in the ALD+T3+CC group. Conversely, compared with the ALD group, expression of pro-IL-1β was significantly increased in the ALD+T3 group and decreased in the ALD+T3+CC group. In conclusion, T3 may reduce the inflammatory response and severity of liver cirrhosis in mice with ALD by negatively regulating the NLRP3 signaling pathway.