**1.1 Oxidative stress**

Oxidative stress is recognized as a disproportion between the production of free radicals (FR) and the antioxidant defenses [8]. Increased levels of prooxidants result in damage to the cell in terms of lipid peroxidation as well as oxidative DNA damage

#### **Figure 1.**

*Molecular mechanisms explaining the hepatoprotective effect of food bioactives. Development of NAFLD/ NASH is induced by different risk factors, such as Western-type diet, physical inactivity, and genetic predisposition. In the presence of obesity and IR, there is an increased flux of FFAs to the liver. These FFAs are stored as TG in lipid droplets leading to hepatic fat accumulation or undergo β-oxidation increasing oxidative stress and the inflammatory pathway. The damaged hepatocyte leads to a further increase of inflammatory signaling (IL-1, TNFa, IL-6) and the recruitment of circulating and residual macrophages (KCs). All of these mechanisms can directly induce the activation of HSCs, the major cell type involved in extracellular matrix deposition and liver fibrosis. The bioactive compounds may exert beneficial effects on NAFLD development and progression by inhibiting lipogenesis, β-oxidation of FFAs, inflammation, and HSCs activation. In the cartoon, we have listed the food bioactives indicating the putative mechanisms by which they may improve liver damage in NAFLD [1].*

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**Figure 2.**

*increasing mitochondrial ROS production [15].*

*Dietary Antioxidants in Experimental Models of Liver Diseases*

and thus protein damage [9]. One or more unelectrified FR atoms or molecules may be present as radical cations or radical anions. They are usually unstable and highly reactive because they can react with molecules and abstract electrons. Oxygen can reduce and produce reactive oxygen species (ROS) with exciting electrons, secondary to the interaction of transition metals or by the addition of energy [9, 10]. Oxidative stress causes fibrogenesis by increasing transforming cytokines including transforming grown factor-beta-1 (TGFβ1), interleukin-6 (IL-6), and tumor necrosis factoralpha (TNFα) [3]. Disruption of the liver metabolism arises from increased quantity of ROS to amplified electron transfer in mitochondrial B-oxidation and increased expression and activity of Cyp2el that is from CYP450 family [11]. Intense production of Cyp2e1 is present because of much more consumption of ethanol which is produced by virtue of a lot of direct and indirect mechanisms [12–14] (**Figure 2**).

Cells produce FR as a result of metabolic events; however, this is not the only source that can cause oxidative stress in body. The pollutants in the environment such as toxic chemicals as well as radiation cause a significant increase in amount of FR, ROS, and reactive nitrogen species (RNS) [10]. In the body, variety of different cell types and chemical reactions produce ROS, the most important metabolism is the cytochrome P450 metabolism and mitochondria-catalyzed electron transport reactions. Most of the inflammatory conditions are also responsible from ROS production, and important cell types in these processes are neutrophils, eosinophils,

*Mechanisms of enhanced ROS production during hepatocyte damage. Ethanol metabolism promotes strong ROS production in the ER by the inducible CYP. It impairs GSH import in the mitochondria, preventing ROS removal. It also impairs B-oxidation promoting lipid accumulation. ETOH induces lipid-raft clustering and increases iron uptake, promoting Fe2+ leakage from lysosomes and increased Fe2+ loads in mitochondria and ER, resulting in ROS production. Ethanol also reduced the autophagic removal of damaged cellular components. Viral infection challenges the ER protein folding process leading to ROS production and Ca2+ leakage in the cytosol and mitochondria. Increased MAMs formation promotes Ca2+ efflux from ER into mitochondria,* 

*DOI: http://dx.doi.org/10.5772/intechopen.83485*

**1.2 Basic sources of free radicals**

*Dietary Antioxidants in Experimental Models of Liver Diseases DOI: http://dx.doi.org/10.5772/intechopen.83485*

and thus protein damage [9]. One or more unelectrified FR atoms or molecules may be present as radical cations or radical anions. They are usually unstable and highly reactive because they can react with molecules and abstract electrons. Oxygen can reduce and produce reactive oxygen species (ROS) with exciting electrons, secondary to the interaction of transition metals or by the addition of energy [9, 10]. Oxidative stress causes fibrogenesis by increasing transforming cytokines including transforming grown factor-beta-1 (TGFβ1), interleukin-6 (IL-6), and tumor necrosis factoralpha (TNFα) [3]. Disruption of the liver metabolism arises from increased quantity of ROS to amplified electron transfer in mitochondrial B-oxidation and increased expression and activity of Cyp2el that is from CYP450 family [11]. Intense production of Cyp2e1 is present because of much more consumption of ethanol which is produced by virtue of a lot of direct and indirect mechanisms [12–14] (**Figure 2**).
