Akademik Veri Yönetim Sistemi
57TH CONGRESS OF THE EUROPEAN SOCIETIES OF TOXICOLOGY, Ljubljana, Slovenya, 10 - 13 Eylül 2023, cilt.384, sa.2609, ss.295-296
Excessive and chronic alcohol consumption is the most important cause of liver diseases and of liver cirrhosis in particular [1]. And it is a worrying global health problem in many parts of the world as the leading cause of preventable illnesses. Annually, alcohol consumption results in approximately 3 million deaths [2]. Inflammasomes are multi-protein complexes that essential for liver defense against pathogens and danger signals but overactivation plays a role in the pathogenesis of various liver diseases. NLRP3 inflammasome is the most studied inflammasome to date which is characterized by its ability to recognize almost any hazard signal. [3]. The purpose of the study was aimed to examine the effects and compared therapeutic effects of coenzyme Q10 (CoQ10) and it's analogue idebenone (IDE) on ethanol-induced liver fibrosis via NLRP3/Caspase-1/IL-1β signaling pathway. For this purpose, to induce liver fibrosis in rats gradually increasing dosages of ethanol (from 2 to 6 g/kg/day) were administered orally over 30 days. Thereafter, two different doses of CoQ10 (10 mg/kg and 20 mg/kg) and IDE (50 mg/kg and 100 mg/kg) were given with ethanol to evaluate the protective effect on ethanol-induced liver fibrosis rat model. Serum alanine transaminase (ALT) and aspartate transaminase (AST) levels were performed and tissue oxidative parameters superoxide dismutase (SOD) activity and glutathione (GSH) levels were evaluated. To evaluate NLRP3/Caspase-1/IL-1β pathway and the fibrosis in liver; molecular analysis of NLRP3, caspase-1, IL-1β and TGF-β mRNA expressions were also studied with RT-PCR method. Ethanol toxicity led to increase in hepatotoxicity markers ALT and AST (both, p<0.001) and also reduced oxidative stress parameters SOD activity and GSH levels (both, p<0.001). TGF-β mRNA expressions increased as an indicator of fibrosis in parallel to increased NLRP3, caspase-1 and IL-1β mRNA expressions significantly (both, p<0.001). CoQ10 and IDE improved in a dose-dependent manner of all these parameters and prevent ethanol-induced liver fibrosis through NLRP3/caspase-1/IL-1β pathway inhibition but CoQ10 is clearly more effective. Both are promising preventing agents but CoQ10 is more effective in ethanol-induced liver fibrosis by inhibiting NLRP3/Caspase-1/IL-1β inflammasome pathway.