Role of oxidative stress in the pathogenesis of nonalcoholic steatohepatitis

Physiological concentrations of unconjugated bilirubin prevent oxidative stress-induced hepatocanalicular dysfunction and cholestasis

“…Another example is non-alcoholic fatty liver disease. Even when OS is critically involved in both onset and progression of the disease (Rolo et al 2012), histological images reveal that the few patients displaying cholestatic features have ductular rather than hepatocellular damage (Sorrentino et al 2005). The discrepancy between the relatively low cholestatic impact of OS in clinical hepatopathies and the well-established evidence that OS is highly cholestatic when studied in in vitro models (e.g.…”

Efficacy of Tumor Necrosis Factor and Interleukin-10 Analysis in the Follow-up of Nonalcoholic Fatty Liver Disease Progression

“…NAFLD is the most common growing public health problem worldwide presenting a wide spectrum of conditions ranging from fatty liver, that in general follows a benign nonprogressive clinical course, to nonalcoholic steatohepatitis (NASH), a serious form of NAFLD, that may progress to cirrhosis and end-stage liver disease with an increasing incidence in obesity, hyperlipidemia and insulin resistance (higher than normal insulin concentrations are needed to achieve normal metabolic responses) [1,11,19]. In this regard, fatty liver disease is a major contributor to cardiovascular and overall obesity-related morbidity and mortality [20].…”

“…Thus, it evident that the increase in serum TNF-a and the decrease in serum IL-10 becomes more prominent as the case becomes complicated during progression of the NAFLD. In addition, TNF-a accelerates the hepatic synthesis of other cytokines, enhances neutrophils chemotaxis and leads to a severe inflammatory response, which results in hepatosteatosis and necrosis in the liver [11]. These results are confirmed with Uysal et al [36] who suggest that liver iron and fat accumulation, oxidant stress, and inflammatory cytokines are closely related in which levels of serum ferritin, malonaldehyde, IL-6, TNF-a and IL-8 could represent the indices of activity and progression of NASH.…”

“…NASH progression is mediated by an inflammatory process in the liver with concomitant tissue damage and fibrosis [7]. The gene expression of proinflammatory cytokines like tumor necrosis factor-alpha (TNF-a) and TNF receptors is increased in the liver of patients with NASH compared with both normal liver and fatty liver, and the expression is higher in those patients with more severe NASH [11].…”

“…Therefore, the balance between pro-and antiinflammatory acting cytokines appears to play a key role in hepatic and systemic insulin action, and they are supposed to have important functions in the development of NAFLD [15]. Neutralization of TNF-a activity improves insulin resistance and fatty liver disease in animals [11]. Therefore, the aim of the present study was to investigate the levels of proinflammatory cytokine (TNF-a) along with the anti-inflammatory cytokine (IL-10) in development and progression of NAFLD from simple steatosis to NASH and fibrosis in Egyptian diabetic patients, and to correlate the relationship between cytokine levels and progression of NAFLD.…”