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Received Jan 4, 2018; Accepted Feb 19, 2018
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1. Introduction
Reactive oxygen species (ROS) are oxygen-containing chemical species including superoxide anion, hydrogen peroxide (H2O2), and hydroxyl radicals, and most of which are produced by mitochondria and nicotinamide adenine dinucleotide phosphate (NADPH) oxidases [1]. Of note, excess of ROS could lead to oxidative stress in cells. Oxidative stress is associated with the disorder of proteins, lipid oxidation, and nucleic acid breaks, which may further impair cellular physiological functions. Numerous studies suggested that oxidative stress may result in some pathogenic diseases, such as cancer [2], neurological disorders [3], age-related diseases [4], atherosclerosis [5], inflammation [6], and cardiovascular diseases [7]. Mammals have evolved a series of antioxidant defenses to protect vital biomolecules from oxidative damage. On the one hand, antioxidant agents, such as antioxidant enzymes like superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), or nonenzymatic agents, such as glutathione (GSH), vitamin C, and vitamin E, can clean off most of ROS [8]. On the other hand, the excess ROS can also activate many signaling pathways such as mitogen-activated protein kinase (MAPKs), NF-erythroid 2-related factor/antioxidant response element (Nrf2/ARE), and peroxisome proliferator-activated receptor γ (PPARγ), which play a vital role in cellular redox homeostasis and contribute to antioxidative defense [9].
Glutamate, as a precursor of GSH, exerts alleviative effects on oxidative stress in medicine and surgery [10]. AKG, as a precursor of glutamine, is cheaper and more stable than glutamine and acts as an antioxidant instead of glutamine in many cellular processes. Many reports demonstrated that AKG can be converted into glutamine by glutamate dehydrogenase (GDH) and glutamine synthetase (GS), which is a sign of antioxidative function. It is evident that AKG could improve antioxidative capacity by promoting glutamine content and antioxidative systems [11, 12]. Additionally, Chen et al. showed that AKG could significantly improve SOD activity but reduce malondialdehyde (MDA) level, suggesting an improvement of intestinal antioxidative capacity [13]. Recently, more and more studies indicated that AKG could improve antioxidative function against oxidative imbalance in cells, which further contributed to the...