Is rat liver affected by non‐alcoholic steatosis more susceptible to the acute toxic effect of thioacetamide?

摘要: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic in developed countries and its prevalence increasing. NAFLD refers to a wide spectrum of damage, ranging from simple steatosis non-alcoholic steatohepatitis, advanced fibrosis, cirrhosis or even cancer. Insulin resistance seems be key ethiopathogenic factor development (Chitturi et al. 2002). Mitochondrial dysfunction (Vendemiale 2001), increased oxidative stress (Gambino 2010) changes glutathione content (Videla 2004), cytokine adipokine imbalance (Tarantino play also important roles pathogenesis NAFLD. These factors may enhance sensitivity acute toxic injury. Despite that, there are only few experiments demonstrating enhanced susceptibility injury In addition, some authors were not successful finding with damage (Avni 2004). Thioacetamide (TAA) thiono-sulphur-containing compound, which has been frequently used industry past. Administration one dose TAA leads characterized by centrilobular necrosis subsequent regenerative response (Mangipudy 1995; Chen 2008). Chronic exposure causes hepatic tumours develop (Natarajan 2006). Metabolic activation TAA, cytochrome P450 (esp. 2E1), but unlikely flavin adenine dinucleotide monooxygenases (Wang 2000), required for effect. After metabolic activation, TAA-intermediates reactive oxygen species can covalently bind biologically molecules increase cellular (Chilakapati 2007; Pallottini 2006), lipid peroxidation, deplete (Sanz Both apoptosis appear process cell death after application (Apte Acute effect dependent, well reproducible, specific region liver, thus often as model hepatotoxin vivo (Cervinkova & Drahota 1998; Shapiro 2006) less vitro (Staňkovaet experiments. The aim this project was compare on intact rat affected high-fat diet-induced find out whether more sensitive caused TAA. Because exerts high similarity human failure (Belanger Butterworth 2005), we chose our study.