Taking a Look at Oxidative Stress

With all living organisms, a process known as cell respiration is integral in order to provide the body with an essential form of energy, adenosine triphosphate (ATP). Oxygen, although an essential part of this process, can form reactants from colliding with electrons associated with carrier molecules. (pb101.rcsb.org, 2017). Hydrogen peroxide is an integral product of this reaction but is known to impose negative effects on the body if high levels are introduced. Explicitly, this reaction is caused “If oxygen runs into (one of these) carrier molecules, the electron may be accidentally transferred to it. This converts oxygen into dangerous compounds such as superoxide radicals and hydrogen peroxide, which can attack the delicate sulphur atoms and metal ions in proteins.” (pdbh101.rcb.org, 2017). Research has suggested that the hydrogen peroxide can be converted into hydroxyl radicals, known to mutate DNA, which can potentially cause bodily harm due to DNA’s role in the synthesis of proteins. These radicals can cause detrimental effects on the human body, and studies have suggested a link to ageing. Due to the harmful effects of these H2o2, it is important that the body finds a way to dispose of hydrogen peroxide before concentrations are too great.

Xenobiotic metabolism is usually divided to phase I and II, where polar function groups are unmasked or introduced to the chemical structure (phase I or activation), followed by the conjugation between the xenobiotic and endogenous molecules, notably glucuronic acid, to further improve hydrophilicity (phase II or conjugation) (Golan 2012). Hepatic microsomal P450 are the enzymes that dominate the catalysis of phase I metabolism of xenobiotics (Table 1 and 2) (Anzenbacher and Anzenbacherova 2001). Therefore,

As a widely used analgesic and antipyretic agent, acetaminophen (APAP) overdose induced hepatotoxicity is one of the most common causes of acute liver failure in the USA and in most Western European countries [1]. Although a number of studies have forced on the influences of N-acetyl-p-benzoquinone imine (NAPQI), a highly reactive metabolite of APAP that depletes hepatic glutathione, and increases in oxidative stress during APAP toxicity [2], other mechanisms such as immune response also raise the susceptibility in the early stages of APAP-induced liver injury [3]. Accumulating evidence demonstrates a critical role of inflammatory cytokine released in early liver damage after APAP intoxication [4, 5]. Kupffer cells (KCs), the liver resident macrophages, are major sources of reactive oxygen species (ROS) and inflammatory

Main compounds of the enzymatic antioxidant system are three, namely, SOD, CAT and tT which have an important role in detoxifying of H2O2 and superoxide anion in cells. Ample of hepatotoxic drugs induces the liver damage by lipid peroxidation indirectly or directly. The proxy radicals are main factors that mediate lipid peroxidation leading to liver injury and kidney damage(41). MDA as a main reactive aldehyde appears during polyunsaturated fatty acid peroxidation in the biological

Several Ames tests have shown that ClPAH has mutagenic potential in Salmonella typhimurim TA98 and TA100 (Bhatia et al., 1987; Nilson and Oestman, 1993). It has also been proven in yeast that ClPAHs function by binding to and activating the Aryl Hydrocarbon Receptor (AhR) and transporting it to the nucleus, where it forms a heterodimer with the AhR nuclear translator protein (ARNT) and transcribes many genes, including several P450 enzymes (Blankenship et al., 2000). In this study, Kakimoto et al. attempted to determine the adverse effects on human health of 1-chloropyrene (ClPyr) by treating it with P450 enzymes 1A1, 1B1, and 1A2 to produce three different oxidative metabolites. These oxidative metabolites are also able to bind to and activate human AhR. The authors believe that the ClPyr metabolites can be used as biomarkers to determine human exposure

These superoxides may be dangerous because they alter the structure of iron and protein via reduction. They may also undergo dismutation to form hydrogen peroxide which, in turn, gives rise to hydroxyl radicals, the most reactive ROS (Gulumian and Van Wyk, 1987; Agarwal et al., 2005). Hydrogen peroxide is not a free radical but its neutral charge allows it to pass through cell membranes and so this makes it very dangerous (Kurutas, 2015). Other internal or endogenous sources for these free radicals are inflammation, xanthine oxidase, peroxisomes, phagocytosis, exercise and ischaemia. Exogenous factors which lead to the development of these ROS include smoking, ozone, environmental pollutants, radiation, pesticides and drugs (Lobo et al.,

In Phase I, we explained how the liver turns a lipid-soluble toxin into a water-soluble compound. But there is a problem. First, the Phase I reactions are just intermediate.

Superoxide dismutase 1 is the most commonly ALS aggregated protein to be identified since its discovery over two decades ago (Rosen et al., 1993; Tortelli et al., 2013). SOD1 is a 153 amino acid homodimer with a copper-zinc active site (Brotherton et al., 2013; Dangoumau et al., 2014). Mutant SOD1 is responsible for the loss of motor neurons and constitutes an estimated 20% of the familial ALS (fALS) cases (Brotherton et al., 2013; Tortelli et al., 2013). Wild type SOD1 is universally expressed in all cells and is responsible for the removal of free radicals often in the form of reactive oxygen species (ROS) (Brotherton et al., 2013; Chiang et al., 2017). Damage to DNA and degradation to metabolic processes occur due to accumulation of ROS

Victims of Tylenol poisoning were reported to suffer from hypoxia, lack or suffocation of oxygen. This is because the victims tested positive for cyanide. Cyanide is a poison that affects complex IV (cytochrome c oxidase) of the electron transport chain . The cytochrome c oxidase accepts electrons from cytochrome c. It then reduced O2 to two molecules of H2O . Cyanide attaches to the iron (Fe) in this protein, and prevents the process from continuing normally. The bond is tight and does not allow any transport of electrons to oxygen. In a domino effect, this stops the production of ATP because ATP synthase does not receive the H+ ions it needs, causing the electron transport chain to stop working properly .

T2DM is the most common form of diabetes, and is caused by a progressive insulin secretory defect against a background of insulin resistance [7]. Its relationship with oxidative stress may reflect the excess levels of reactive oxygen species in hyperglycemia. Oxidative stress has a huge impact on the etiology, pathogenesis, and complications of T2DM [8, 9]. In T2DM the major antioxidant enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) have an altered activity [5] and [6].In its protective role against oxidative stress, selenium has drawn increasing attention for preventing type 2 diabetes mellitus (T2DM), cardiovascular disease, cancer, and other chronic diseases [4, 5, 6]. Low selenium levels are thought to contribute to disease etiology, or may be a consequence of disease that aggravates the condition further [1].

To fully understand the biological role of isoketals in oxidative injury and counter their detrimental effects, efforts to identify selective scavengers of isoketals were undertaken. A lead compound, pyridoxamine (PM) was first discovered as a carbonyl scavenger in 1996 by Billy G. Hudson and colleages (Booth, Khalifah et al. 1996), and identified through initial screens, where Amarnath and colleagues determined second-order reaction rates for a series of primary amines relative to N-α-acetyl-lysine (Amarnath, Amarnath et al. 2004). Pyridoxamine is a vitamer in the vitamin B6 family, and through our studies, PM was found to effectively intercept isoketals from adducting to cellular amines. Through the initial screen, pyridoxamine was found

one) of ATP. This happens in the mitochondria of muscle cells; the increase of size and quantity will

In 1990, Morrow, Roberts, and colleagues reported the formation of prostaglandin (PG)-like compounds in vivo, termed isoprostanes, by free radical-induced peroxidation of arachidonic acid (Morrow, Harris et al. 1990). Analogous to the cyclooxygenase enzymatic pathway, intermediates in the IsoP pathway are PGH2-like bicyclic endoperoxides. In aqueous media, PGH2 is unstable and undergoes rearrangement to form -ketoaldehydes, levulinaldehyde derivatives termed levuglandin E2 and D2 (Salomon, Miller et al. 1984). Levuglandins comprise approximately 20% of the total rearrangement products of PGH2. Considering that the IsoP endoperoxides undergo rearrangement in vivo to form E2-IsoPs, D2-IsoPs, and isothromboxanes along with F2-IsoPs (Morrow, Minton et al. 1994, Morrow, Awad

The authors could use CYP27A1 knocked out mice to find the effect of the drugs on cholesterol conversion without the CYP27A1 enzyme activity. In addition to that, they also could measure the CYP27A1 mRNA expression for the drug treatments, to find the effect on CYP27A1 enzyme

The reactivity of HOCl has been comprehensively assessed with in a wide range of cellular systems, including yeast (Carmona-Gutierrez et al., 2013) and bacteria (Winterbourne and Kettle, 2013; Winterbourne et al., 2006; Chapman et al., 2002), together with many studies focused on specific mammalian cell types and tissues. It is clear from the numerous invitro studies that HOCl is highly reactive and destructive, inducing cell death via both necrotic and programmed apoptotic pathways, depending on the oxidant concentration and cell type under study.