Oxidative Stress Case Study

Normally, there is a balance between tissue oxidant and antioxidant activity. The latter is achieved by the antioxidant scavenger system, which includes enzymes like superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and antioxidant vitamins (C, A, E and other carotenoids) (Gil et al., 2017) . Oxidative stress is a

[98, 99]. The detrimental effects of ROS become more pronounced with age due to the limits of cellular antioxidant defense systems.

Usually, the body is able to cope with free radicals, however, if there are lots of free radicals being produced, great damage can be done unless something is done. Vitamins E and C are two antioxidants that are used to stop, or

Superoxide dismutase (SOD) is an enzyme that alternately catalyzes the partitioning of superoxide anion O2− to convert it to hydrogen peroxide H2O2 and molecular oxygen O2 [79, 80]. SOD plays significant protective roles versus cellular and histological damage that occur by ROS. It facilitates the transformation of superoxide radicals to hydrogen peroxide H2O2, and in the existence of other enzymes it converts H2O2 to O2and H2O [81]. In mammalian tissues there are three forms of SOD: Cu-Zn-SOD, Mn-SOD, and EC-SOD, and each form of them are having a special gene [82, 83]. Cu-Zn-SOD called SOD is centralized in cytosol, Mn-SOD also known SOD 2 found in mitochondria, and EC-SOD or SOD 3 localized in extracellular space [84, 85]. Superoxide interacts rapidly with nitric oxide (NO), decrease the activity of NO and generating the oxidative peroxy nitrite radical [86].

Glutathione helps to protect cells from reactive oxygen species. GSH checks free radical damage and helps detoxification by conjugating with chemicals. Increase in reactive oxygen species protection causes GSH depletion. GSH acts as cofactor for Glutathione Peroxidase (GPx) and Glutathione-S-transferase (GST). Glutathione-S-transferase is thought to play a physiological role in initiating the detoxification and these enzymes catalyse the reaction of such compounds with the -SH group of glutathione, thereby neutralizing their electrophilic sites and rendering the products more water-soluble. GPx is present throughout the tissues as four different isoenzymes, cellular, extracellular glutathione peroxidase, as phospholipid hydroperoxide glutathione peroxidase and gastrointestinal glutathione peroxidase (Alam et al 2013). GPx low activity is one of the early consequences of a disturbance of the prooxidant or antioxidant balance due to toxic exposure. Glutathione reductase plays an important role in maintaining a basic GSH pool, via catalysing the reduction of glutathione disulfide (GSSG) to GSH in NADPH-dependent reaction (Yao Chen et al

Abstract: Atherosclerosis is a disease in which plaque builds up inside the arteries. Arteries are blood vessels that carry oxygen-rich blood to the heart and other parts of the body. Reactive oxygen species are common by-products of many oxidative biochemical and physiological processes. They can be released by NAD(P)H oxidase, nitric oxide synthase and xanthine oxidase and activates various signaling pathways that underlie vascular inflammation in atherogenesis thus leading to oxidative stress induced tissue injury. Therefore, it is important to consider the sources of oxidants in the context of available antioxidants such as ascorbic acid, tocopherol, β-carotene, superoxide

However, an imbalance in the production and elimination of ROS is associated with human diseases (68). ROS molecules are produced by the host enzyme NADPH oxidase (NOX). Seven NOX homologues are encoded in the human genome. NOX2 (otherwise known as gp91Phox) is the best-characterized family member in terms of its regulation. Gp91Phox is the catalytic unit of this multicomponent oxidase whereas p22Phox, p40Phox, p47Phox, p67Phox and the small GTPase RAC are regulatory subunits. Exposure of cells to pathogens triggers the assembly of cytosolic regulatory subunit (p40Phox, p47Phox, p67Phox and RAC) with transmembrane protein complex formed by gp91Phox and p22Phox (47). NOX2 mediates the transfer of an electron from NADPH to O2, forming the superoxide radical (O2̇ ˉ) (47). The superoxide radical is converted to hydrogen peroxide by superoxide dismutase. In the phagolysosome of neutrophils, myeloperoxidase (MPO) catalyzes the generation of hypochlorite (HOCl) from hydrogen peroxide. HOCl dramatically enhances the microbicidal activity of hydrogen peroxide (92). Pro-inflammatory cytokines such as IL-1 and TNF-α upregulate the expression of inducible nitric oxide synthase (iNOS), which produces nitric oxide from the amino acid L-arginine. Nitric oxide reacts with superoxide to generate peroxynitrite (OONO-), a potent nitrating agent and oxidant (Figure 2D) (31). Both RNS and ROS

X.-M. Li, Department of Psychiatry, Faculty of Medicine, University of Manitoba, PZ432-771 Bannatyne Avenue, Winnipeg, Manitoba, Canada

For the treatment of many diseases, particularly cancer, substantial attention is presently focused on the use of drugs without side effects and to study the underlying mechanisms of their actions. Precisely, the action of endogenous enzymatic antioxidants capable of eliminating the oxidants and free radicals accountable for cancer initiation and progression, have been extensively debated [27]. Molecular uncovering of the antioxidant physiognomies of different anticancer drugs in addition to food and environmental substantces have been implemented [28]. Cellular antioxidantive enzymes have been inspected for their role in inhibition of diseases such as cancer, coronary heart disease and also altitude sickness [29]. The antioxidant

The consumption of oxygen that is incompletely used in the human body may lead to cellular damages. This can happen due to interaction of free radicals oxygen molecules with the certain problematic molecules in the body cell, such as toxins. Free radicals are made up of unpaired or odd numbers of electrons where it will exist as a reactive trouble maker toward the body cell by start a chain reaction of damage to healthy cells. This condition will stimulates and change the character and function of free radicals as they combine in unnatural ways, then causing a DNA and cellular damages simultaneously. Thus, the healthy cells will be function poorly or even die.

Renal injury due to KBrO3 intoxication could be evaluated by assessment of serum urea, creatinine, and uric acid, which were used as early indicators of renal dysfunction [39].The significant increase in serum urea, creatinine and uric acid in the KBrO3 -treated rats indicate the development of renal dysfunction and reduced glomerular filtration rate. The increase in uric acid level also may be due to degradation of purines and pyrimidines which strongly related to the significant increase in xanthine oxidase activity resulted in overproduction of uric acid. The increase in xanthine oxidase activity does not only catalyze the formation of uric acid but also generate ROS. Therefore, the elevated xanthine oxidase activity could explain the

The present study indicated that increase activation ROS, p-JNK, p-ERK, p-p38 levels in CA group as compared to sham group at 72h of reperfusion. Compared to CA group, only treatment with inhibitor of p38 induced ROS increased, survival rate and NDS reduced and hippocampal injury while treatment with JNK inhibitor or ERK inhibitor reduced markedly ROS, increased survival rate and NDS and didn’t lead hippocampal cell injury. The results indicated that activation JNK and ERK may be involved in neuronal cell death while activation of p38 may be involved in neuroprotection in rat subjected to CA/CPR.

To address this possibility, SK-N-BE(2)M17 and MN9D cells will be exposed to 50, 100, and 200 µM H2O2 for 4 days (concentration course) or 200 µM H2O2 for 1, 2 and 4 days (time course). After several sets of exposures, cells will be harvested for different measurements: intracellular ROS by DCFH2-DA assay, reduced form of glutathione (GSH) by the fluorescent probe monochlorobimane assay, levels of Cu/Zn superoxide dismutase 1 (SOD1) by western blotting and cell viability (MTT assay), respectively. Similar experiments and measurements will be carried out in primary cultures from the mouse ventral mesencephalon and LC to verify the findings in cell lines.

The high MDA level mentioned in Cd-group our investigation was associated with a marked depletion of renal GSH by Cd exposure due to the direct binding of Cd to enzyme active sites, if it contains –SHgroups77. Significant decrease in the levels of these non-enzymatic antioxidants in Cd toxicity could lead to increased susceptibility of the renal tissue to free radical damage .GSH is a non-enzymatic antioxidant which acts as a first line of defense against oxidative stress78. The significant reduction in GSH levels that was recorded can be attributed to the increased use of GSH (by the renal tissues) to mop up excessive ROS that were generated during the process of Cd-induced renal injury 60. The depletion of GSH also seems to be a prime

induced renal toxicity(Bozkurt et al., 2014). Garlic has been selected due to its antioxidant and antiradical