Abstract
Cholestatic liver injury, due to obstruction of the biliary tract or genetic defects, is often accompanied by progressive inflammation and liver fibrosis. Methane-rich saline (MRS) has anti-inflammatory properties. However, whether MRS can provide protective effect in cholestatic liver injury is still unclear. In this study, Sprague-Dawley rats received bile duct ligation (BDL) to generate a cholestatic model followed by MRS treatment (10 mL/kg, ip treatment) every 12 h after the operation to explore the potential protective mechanism of MRS in cholestatic liver injury. We found that MRS effectively improved liver function, alleviated liver pathological damage, and localized infiltration of inflammatory cells. MRS treatment decreased the expression of hepatic fibrosis-associated proteins to alleviate liver fibrosis. Furthermore, MRS treatment suppressed the TLR4/NF-κB pathway and further reduced the levels of proinflammatory factors. Downregulation of NF-κB subsequently reduced the NLRP3 expression to inhibit pyroptosis. Our data indicated that methane treatment prevented cholestatic liver injury via anti-inflammatory properties that involved the TLR4/NF-κB/NLRP3 signaling pathway.
Highlights
Due to obstruction of the biliary tract or genetic defects, cholestasis is a widespread clinical liver disease
Cholestatic liver injury occurs in many diseases, such as cholestasis during pregnancy, primary sclerosing cholangitis (PSC), druginduced cholestasis liver disease, and cholestasis liver disease caused by various types of viral hepatitis [1]
TLR4 recognizes the LPS leading to the activation of NF-κB, translocating NF-κB to the nucleus, and secreting the proinflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) [4]
Summary
Due to obstruction of the biliary tract or genetic defects, cholestasis is a widespread clinical liver disease. The accumulation of highly toxic bile acid causes cholestatic liver damage, hepatic inflammation, proliferation of hepatic stellate cells (HSCs), and hepatic fibrosis, cirrhosis, and death [2]. The detailed mechanism of the initiation of inflammation induced by toxic bile acid is still unknown [3]. Toll-like receptors (TLRs) are a key member of the cellular transmembrane receptors and pathogenic membrane recognition receptors in the innate immunity. TLRs activate the immune response by recognizing invasive pathogens and promote the release of inflammatory cytokines via interactions with NF-κB. TLR4 recognizes the LPS leading to the activation of NF-κB, translocating NF-κB to the nucleus, and secreting the proinflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) [4]. NLRP3, activated by Oxidative Medicine and Cellular Longevity
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