Conclusion
Our results speculated that by inhibiting the SIRT1- NF-κB pathway and NLRP3 inflammasome, SAL defends against LPS-induced liver injury and inflammation.
Methods
Six to eight-week-old male C57BL/6 wild-type mice were intraperitoneally treated with 10 mg/kg LPS for 24 hr and 50 mg/kg SAL two hours before LPS administration. Mice were categorized into control, LPS, and LPS + SAL groups. To evaluate liver injury, biochemical and TUNNEL staining test studies were performed. The Elisa assay analyzed interleukin- 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) pro-inflammatory cytokine expression levels. RT-qPCR and western blotting measured mRNA and protein expression of SIRT1, NF-кB, NLRP3, cleaved caspase-1, and GSDMD, respectively.
Results
Analysis of the serum alanine/aspartate aminotransferases (ALT/AST), malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) revealed that SAL protected against hepatotoxicity induced by LPS. The pathological evaluation of the liver supported the protection provided by SAL. SAL treatment reversed IL-1β, TNF-α, and IL-6 pro-inflammatory cytokines after being induced by LPS (all, P<0.001). The western blotting examination results demonstrated that SAL increased the levels of Sirtuin 1 (SIRT1) expression but markedly reduced the phosphorylation of Nuclear Factor Kappa B (NF-B) and the expressions of NLRP3, cleaved caspase-1, and gasdermin D (GSDMD) induced by LPS (all, P<0.001).