Oxidative stress, arsenic

Hughes, M.F. and Kitchin, K.T. (2006) Arsenic, oxidative stress and carcinogenesis, in Oxidative Stress, Disease and Cancer (ed. K.K. Singh), Imperial College Press, London, pp. 825-50. 

Gupta, S. et al., Arsenic trioxide induces apoptosis in peripheral blood T lymphocyte subsets by inducing oxidative stress A role of Bcl-2, Mol. Cancer Then, 2,711, 2003. 

On the other hand, several ROS are highly cytotoxic. Consequently, eukaryotic cells have developed an elaborate arsenal of antioxidant mechanisms to neutrahze their deleterious effects (enzymes such as superoxide dismutases, catalases, glutathione peroxidases, thioredoxin inhibitors of free-radical chain reaction such as tocopherol, carotenoids, ascorbic acid chelating proteins such as lactoferrin and transferrin). It can be postulated that ROS may induce an oxidative stress leading to cell death when the level of intracellular ROS exceeds an undefined threshold. Indeed, numerous observations have shown that ROS are mediators of cell death, particularly apoptosis (Maziere et al., 2000 Girotti, 1998 Kinscherf et al., 1998 Suzuki et al., 1997 Buttke and Sanstrom, 1994 Albina et al., 1993). 

Arsenic compounds are thought to exert their toxic effects by several modes of action. Interference with enzyme function may result from sulfhydryl group binding by trivalent arsenic or by substitution for phosphate. Inorganic arsenic or its metabolites may induce oxidative stress, alter gene expression, and interfere with cell signal transduction. Although on a... 

Arsenic has been shown to induce oxidative stress (Shi, Shi and Liu, 2004 Hughes and Kitchin, 2006). Oxidative stress is a result of an imbalance between reactive oxygen species and the ability of a cell s antioxidant defense apparatus to respond. Oxidative stress can result in the damage of proteins, lipids, RNA, and deoxyribonucleic acid (DNA). In addition, since oxidant species have a role in cell signaling, a state of oxidative stress could potentially alter signaling within and between cells. 

DNA isolated from cells (Kessel et al., 2002) and tissues and urine of animals (Vijayaraghavan et al., 2001 Yamanaka et al., 2001) treated with arsenic show lesions induced by oxidative stress. These lesions include 8-oxo-2 -deoxyguanosine and 8-hydroxy-2 -deoxyguanosine. These DNA lesions may lead to base-pair substitutions (guanine to thymidine and adenine to cytosine) during DNA synthesis, which could lead to altered gene products. 

The mechanism for arsenic-induced oxidative stress injury is not known with certainty. It may occur as a consequence of free radical production due to redox cycling of As(III) and As(V), release of iron from... 

Bhadauria, S., Flora, S.J.S. (2007). Response of arsenic induced oxidative stress, DNA damage and metal imbalance to combined administration of DMSA and monoisoamyl DMSA during chronic arsenic poisoning in rats. Cell Biol. Toxicol. 23 91-104. 

Flora, S.J.S. (1999). Arsenic induced oxidative stress and its reversibility following combined administration of N-acetylcysteine and meso 2,3 dimercaptosuccinic acid in rats. Clin. Exp. Pharmacol. Physiol. 26 865-9. 

Flora, S.J.S., Bhadauria, S., Pant, S.C., Dhaked, R.K. (2005). Arsenic induced blood and brain oxidative stress and its response to some thiol chelators in rats. Life Set 77 2324-37. 

Karman, G.M., Flora, S.J.S. (2006). Combined administration of N-acetylcysteine (NAC) and monoisoamyl DMSA on tissue oxidative stress during arsenic chelation therapy. Biol. Trace Elem. Res. 110 43-60. 

Kinoshita, A., Wanibuchi, H., Wei, M., Yunokl, T., Fukushima, S. (2007). Elevation of 8-hydroxydeoxyguanosine and cell proliferation via generation of oxidative stress by organic arsenicals contributes to their carcinogenicity in the rat liver and bladder. Toxicol. Appl. Pharmacol. 221 295-305. 

Liu, J., Kaduska, M., Liu, Y., Qu, W., Mason, R.P., Walker, M.P. (2000). Acute arsenic induced free radical production and oxidative stress related gene expression in mice. Toxicologists 54 280-1. 

The co-administration of M. oleifera seed powder with arsenic protects animals from arsenic induced oxidative stress and reduce body arsenic burden (49). Exposure of rats to arsenie (2.5 mg/kg, intraperitoneally for 6 weeks) increases the levels of tissue reaetive oxygen species (ROS), metallothionein (MT) and thiobarbitnrie aeid reaetive substance (TEARS) and is accompanied by a decrease in the aetivities in the antioxidant enzymes such as superoxide dismutase (SOD), eatalase and glutathione peroxidase (GPx). Also, Arsenic exposed mice exhibits hver injury as reflected by reduced acid phosphatase (AGP), alkaline phosphatase (ALP) and aspartate aminotransferase (AST) activities and altered heme synthesis pathway as shown by inhibited blood 8-aminolevulinic acid dehydratase (5-ALAD) activity. Co-administration of M. oleifera seed powder (250 and 500 mg/kg, orally) with arsenie significantly increases the activities of SOD, catalase, GPx with elevation in redueed GSH level in tissues (liver, kidney and brain). These ehanges are accompanied by approximately 57%, 64% and 17% decrease in blood ROS, liver metallothionein (MT) and lipid peroxidation respectively in animal eo-administered with M. oleifera and arsenic. There is a reduced uptake of arsenie in soft tissues (55% in blood, 65% in liver, 54% in kidneys and 34% in brain) following eo-administration of M. oleifera seed powder (particularly at the dose of 500 mg/kg). This points to the fact that administration of M. oleifera seed powder could be beneficial during chelation therapy with a thiol chelator (26). 

Menezes, R.A.. Amaral, C., Batista-Nascimento, L., Santos, C., Ferreira, R.B.. Devaux, F., Fleutherio, E.C., and Rodrigues-Pousada, C. (2008) Contribution of Yapl towards S. cerevisiae adaptation to arsenic mediated oxidative stress. The Biochemical Journal, 414 (2), 301-311. 

Kalia, K. Narula, G.D. Kannan, G.M. Flora, S.J.S. Effects of combined administration of captopril and DMSA on arsenite induced oxidative stress and blood and tissue arsenic concentration in rats. Comp. Biochem. Physiol. C. Toxicol. Pharmacol. 2007,144 (4), 372-379. 

The majority of literature on metal-induced stress proteins results from studies employing the arsenic oxides, sodium arsenate and sodium arsenite (Table 2). Although these compounds are very effective inducers of stress proteins, arsenite has been shown to be the more potent inducer (Bournias-Vardiabasis et al. 1990 Bauman et al. 1993). Sodium arsenite has been shown to elicit thermotolerance, self-tolerance, and cross-tolerance in response to a variety of physiologic stresses (see Sect. D). The thermotolerance induced by arsenite treatment has been correlated with the increase in newly synthesized stress proteins (Lee and Dewey 1987). Arsenite has been shown to induce the same proteins as heat in several experimental systems (De Jong et al. 1986 Bournias-Vardiabasis et al. 1990 Cohen et al. 1991 Honda et al. 1992). In contrast, there are reported differences in the stress protein responses produced by these two stressors. 

Kirk, T. Sarfaraz, A. (2003) Oxidative stress as a possible mode of action for arsenic carcinogenesis. Toxicology Letters, 137,3-13. 

Fowler, B. A., M. H. Whittaker, M. Lipsky, et al. 2004. Oxidative Stress Induced by Lead, Cadmium, and Arsenic Mixtures 30-Day, 90-Day, and 180-Day Drinking Water Studies in Rats An Overview. Biometals 17 567-568. 

Arsenic-induced oxidative stress is well established and is known to play important role in onset or progression of various pathological manifestations. Various oxidative stress-related markers may not prove to be specific biomarkers in arsenic toxicity but they may contribute as important parameters to diagnose early signs of arsenic-induced adverse effects [23 ]. A study with 157 participants in China demonstrated a positive correlation between the levels of serum thioredoxinl and the total water arsenic intake or the levels of urinary arsenic species. Authors suggested that since changes in human serum thioredoxinl can be detected before arsenic-specific dermatological symptoms, it may serve as an early biomarker for the same [24 ]. 

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