Sıçanlarda Subakut Alkol Kullanımına Bağlı Gelişen Karaciğer Fibrozisinde İdebenon ve Koenzim Q10’un Etkisinin NLRP3 İnflamazom Aktivitesi Üzerinden İncelenmesi

Abstract

YOLADI, F.B., Investigation of the Effects of Idebenone and Coenzyme Q10 on Liver Fibrosis Due to Subacute Alcohol Use in Rats through NLRP3 Inflammasome Activity, Hacettepe University Graduate School of Health Sciences, Pharmaceutical Toxicology Program PhD Thesis, Ankara, 2024. One of the main causes of liver fibrosis, a serious health problem, is excessive chronic alcohol consumption. Antifibrotic treatments that can slow, stop or reverse the progression of liver fibrosis are very important. Chronic ethyl alcohol consumption triggers liver damage through excessive NLRP3 inflammasome activation. Coenzyme Q10 (CoQ10) and its synthetic analogue idebenone (IDE) are known for their strong antioxidant effects. However, the hepatoprotective effects of CoQ10 and IDE on the NLRP3 inflammasome signalling pathway in ethyl alcohol-induced liver fibrosis have not yet been investigated. Liver fibrosis was induced in Wistar rats by oral administration of ethyl alcohol in gradually increasing doses (2-6 g/kg/day) over 30 days. The effects of CoQ10 (10 and 20 mg/kg) and IDE (50 and 100 mg/kg) on serum markers of hepatotoxicity (ALT, AST, GGT, ALP ve TBIL) and markers of tissue oxidative stress (superoxide dismutase, glutathione and malondialdehyde) were investigated in rats with fibrosis. Masson's trichrome staining was used to visualize fibrosis in liver tissue. For molecular analysis, mRNA expressions of TGF-β, NF-κB, IL-1β, IL-18, NLRP3 and caspase-1 were measured by RT-PCR method. The findings showed that ethyl alcohol exposure activated the NLRP3/caspase-1/IL-1β pathway, causing hepatotoxicity. It was shown that CoQ10 and IDE caused a dose-dependent improvement in all evaluated parameters, but CoQ10 was more effective. The results were interpreted that CoQ10 and IDE prevented ethyl alcohol-induced liver fibrosis through inhibition of NLRP3 activation.