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Possible mechanisms for induction of oxidative stress and suppression of systemic nitric oxide production caused by exposure to environmental chemicals

  • Review Article
  • Published:
Environmental Health and Preventive Medicine Aims and scope

Abstract

The cytotoxic effects evoked by exposure to environmental chemicals having electrophilic properties are often attributable to covalent attachment to intracellular macromolecules through sulfhydryl groups or enzyme-mediated redox cycling, leading to the generation of reactive oxygen species (ROS). When huge amounts of ROS form they overwhelm antioxidant defenses resulting in the induction of oxidative stress. Nitric oxide (NO) which plays a crucial role in vascular tone, is formed by endothelial NO synthase (eNOS). Since a decrease in systemic NO production is implicated in the pathophysiological actions of vascular diseases, dysfunction of eNOS by environmental chemicals is associated with cardiopulmonary-related diseases and mortality. In this review, we introduce the mechanism-based toxicities (covalent attachment and redox cycling) of electrophiles. Therefore, this review will focus on the possible mechanisms for the induction of oxidative stress and impairment of NO production caused by environmental chemicals.

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Abbreviations

reactive oxygen species:

ROS

NO:

nitric oxide

NOS:

nitric oxide synthase

nNOS:

neuronal NO synthase

M6DH:

morphine 6-dehydrogenase

MDMA:

3,4-methylenedioxymethamphetamine

CYP:

cytochrome P450

DHMA:

3,4-dihydroxymethamphetamine

P450R:

cytochrome P450 reductase

TNT:

2,4,6-trinitrotoluene

DEP:

diesel exhaust particles

8-OHdG:

8-hydroxydeoxyguanosine

E 17 :

one-electron reduction potential

CAM:

calmodulin

BAEC:

bovine aortic endothelial cells

NOx:

nitrite and nitrate

DTT:

dithiothreitol

LPO:

lipid peroxidation

iAsV:

inorganic pentavalent arsenic

BH4 :

(6R)-5,6,7,8-tetrahydrobiopterin

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  1. Department of Environmental Medicine, Institute of Community Medicine, University of Tsukuba, 305-8575, Tsukuba, Ibaraki, Japan

    Yoshito Kumagai & Nobuhiro Shimojo

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  1. Yoshito Kumagai
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Kumagai, Y., Shimojo, N. Possible mechanisms for induction of oxidative stress and suppression of systemic nitric oxide production caused by exposure to environmental chemicals. Environ Health Prev Med 7, 141–150 (2002). https://doi.org/10.1007/BF02897942

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