Amantadine attenuates LPS-associated acute hepatic injury through anti-inflammatory and antiapoptotic responses: potential involvement of TXNIP/NLRP3-related signaling.

The hepatoprotective potential of amantadine (AMN) against lipopolysaccharide (LPS)-triggered hepatic injury was investigated by evaluating inflammation, inflammasome activation, and apoptosis-related signaling pathways. The study consists of four groups: Control, LPS, LPS + AMN, and AMN. Histopathological changes were evaluated in hematoxylin and eosin-stained liver sections. Immunohistochemical analyses were performed to assess C-reactive protein (CRP), serum amyloid A (SAA), and tumor necrosis factor-alpha (TNF-α). Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were measured as biochemical indicators of liver injury. Interleukin-1 beta (IL-1β), interleukin-18 (IL-18), NLR family pyrin domain containing 3 (NLRP3), thioredoxin-interacting protein (TXNIP), and Bcl-2-associated X protein (BAX) gene expression was determined liver tissue. LPS administration caused severe histopathological damage, inflammatory cell infiltration, and significant elevations in AST and ALT activities. Increased immunoreactivity of CRP, SAA, and TNF-α, together with upregulated IL-1β, IL-18, NLRP3, TXNIP, and BAX expression, indicated enhanced inflammatory and apoptotic responses. Administration of AMN was associated with attenuation of tissue damage, accompanied by lower inflammatory marker levels, decreased serum transaminase activities, and altered expression of key genes related to inflammasome activation and apoptotic pathways. No significant differences were detected between the LPS + AMN groups and controls groups. The present findings are consistent with an association between AMN administration and attenuation of LPS-associated hepatic injury, accompanied by changes in inflammatory responses, inflammasome-related signaling, and apoptosis-related pathways. These findings are consistent with a potential hepatoprotective effect of AMN in inflammation-associated liver injury and warrant further investigation.