Oxidative stress is implicated in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). In the present study, hepatic and plasma oxidative stress-related parameters were measured and correlated with clinical and histological findings in 31 NAFLD patients showing increased body mass index. Liver protein carbonyl content was enhanced by 403% in patients with steatosis (n=15) compared with control values (n=12), whereas glutathione content, superoxide dismutase (SOD) activity and the ferric reducing ability of plasma (FRAP) were decreased by 57%, 48% and 21% (P<0.05) respectively. No changes in microsomal p-nitrophenol hydroxylation and the total content of cytochrome P450 (CYP) or CYP2E1 were observed. Patients with steatohepatitis (n=16) exhibited protein carbonyl content comparable with that of controls, whereas glutathione content, SOD and catalase activities were decreased by 27%, 64% and 48% (P<0.05). In addition, FRAP values in patients with steatohepatitis were reduced by 33% and 15% (P<0.05) when compared with controls and patients with steatosis respectively, whereas p-nitrophenol hydroxylation (52%) and CYP2E1 content (142%) were significantly increased (P<0.05) compared with controls. It is concluded that oxidative stress is developed in the liver of NAFLD patients with steatosis and is exacerbated further in patients with steatohepatitis, which is associated with CYP2E1 induction. Substantial protein oxidation is followed by proteolysis of the modified proteins, which may explain the co-existence of a diminished antioxidant capacity and protein oxidation in the liver of patients with steatohepatitis.

Non-alcoholic fatty liver disease (NAFLD) is the most important cause of chronic liver disease that is characterized by hepatocyte triacylglycerol accumulation (steatosis), which can progress to inflammation, fibrosis, and cirrhosis (steatohepatitis). Overnutrition triggers the onset of oxidative stress in the liver due to higher availability and oxidation of fatty acids (FA), with development of hyperinsulinemia and insulin resistance (IR), and n-3 long-chain polyunsaturated FA (n-3 LCPUFA) depletion, with enhancement in the n-6/n-3 LCPUFA ratio favouring a pro-inflammatory state. These changes may lead to hepatic steatosis by different mechanisms, namely, (i) IR-dependent higher peripheral lipolysis and FA flux to the liver, (ii) n-3 LCPUFA depletion-induced changes in DNA binding activity of sterol regulatory element-binding protein 1c (SREBP-1c) and peroxisome proliferator-activated receptor α (PPAR-α) favouring lipogenesis over FA oxidation, and (iii) hyperinsulinemia-induced activation of lipogenic factor PPAR-γ. Supplementation with n-3 LCPUFA appears to reduce nutritional hepatic steatosis in adults, however, other histopathologic features of NAFLD remain to be studied.

Oxidative stress is a redox imbalance between pro-oxidants and antioxidants in favour of the former ones, leading to different responses depending on the level of pro-oxidants and the duration of the exposure. In this article, we discuss the damaging or cytoprotective signaling mechanisms associated with oxidative stress by addressing (1) the role of prolonged and severe oxidative stress and insulin resistance as determinant factors in the pathogenesis of non-alcoholic fatty liver disease associated with obesity, which, with the concurrence of nutritional factors, may determine the onset of fatty liver and its progression to steatohepatitis; and (2) the development of an acute and mild pro-oxidant state by thyroid hormone administration, which elicits the redox up-regulation of the expression of proteins affording cell protection, as a preconditioning strategy against ischemia-reperfusion liver injury.

Non-alcoholic fatty liver disease (NAFLD) is the main cause of liver disease worldwide. NAFLD is linked to circumstances such as type 2 diabetes, insulin resistance, obesity, hyperlipidemia, and hypertension. Since the obesity figures and related comorbidities are increasing, NAFLD has turned into a liver problem that has become progressively more common. Currently, there is no effective drug therapy for NAFLD; therefore, interventions in lifestyles remain the first line of treatment. Bearing in mind that adherence rates to this type of treatment are poor, great efforts are currently focused on finding novel therapeutic agents for the prevention in the development of hepatic steatosis and its progression to nonalcoholic steatohepatitis and cirrhosis. This review presents a compilation of the scientific evidence found in the last years showing the results of interventions in lifestyle, diet, and behavioral therapies and research results in human, animal and cell models. Possible therapeutic agents ranging from supplementation with vitamins, amino acids, prebiotics, probiotics, symbiotics, polyunsaturated fatty acids and polyphenols to interventions with medicinal plants are analyzed.