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Received Aug 7, 2017; Accepted Jan 23, 2018
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1. Introduction
According to the Harmann theory of aging, oxidative stress is at the base of the mechanisms involved in aging processes [1] and contributes to the development of many age-related diseases including cancer, atherosclerosis, hypertension, diabetes, and neurodegenerative disorders [2–4]. Oxidative stress is defined as the imbalance of the production of free radicals, and the efficiency of antioxidant enzyme systems and the ability to activate antioxidant-promoting intracellular pathways. ROS/RNS are usually produced by living organisms as a result of normal cellular metabolism, but they can also be induced by different endogenous and exogenous insults [5]. Thus, during the life span, the organism is continuously at risk to be exposed to ROS/RNS beyond such a threshold level which the body tissues fail to counteract the damage. It is well known that ROS/RNS take part in physiological cell processes from low to moderate concentrations, but at high concentrations, they produce adverse modifications to the cellular macromolecules such as lipids, proteins, and DNA, affecting cell functions and survival [3, 6]. Antioxidant enzyme cascade such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) acts as the first line of protection in counteracting ROS/RNS generation. These three enzymes work sequentially to neutralize free radicals. SOD catalyzes the dismutation of superoxide anion to H2O2, which is in turn neutralized to H2O by CAT or GPx [7]. In addition, antioxidant-promoting intracellular pathways contribute in maintaining redox steady state and in preventing ROS/RNS detrimental effects induced by stressors. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) transcription factor has emerged as a master regulator of cellular detoxification response and redox status since it protects the organism from pathologies caused or exacerbated by oxidative stress. A key role of the Nrf2 pathway has also emerged in the aging processes and in age-related diseases [8–10]. The Nrf2 pathway is an intrinsic mechanism to defense oxidative stress by inducing the transcription of up to 10% of human genes, which take part in different cellular functions such as ROS/RNS elimination, detoxification,...