Mechanisms of the Antioxidant Effects of Nitric Oxide

Duke University, Durham, North Carolina, United States
Antioxidants and Redox Signaling (Impact Factor: 7.41). 05/2001; 3(2):203-13. DOI: 10.1089/152308601300185179
Source: PubMed


The Janus face of nitric oxide (NO) has prompted a debate as to whether NO plays a deleterious or protective role in tissue injury. There are a number of reactive nitrogen oxide species, such as N2O3 and ONOO-, that can alter critical cellular components under high local concentrations of NO. However, NO can also abate the oxidation chemistry mediated by reactive oxygen species such as H2O2 and O2- that occurs at physiological levels of NO. In addition to the antioxidant chemistry, NO protects against cell death mediated by H2O2, alkylhydroperoxides, and xanthine oxidase. The attenuation of metal/peroxide oxidative chemistry, as well as lipid peroxidation, appears to be the major chemical mechanisms by which NO may limit oxidative injury to mammalian cells. In addition to these chemical and biochemical properties, NO can modulate cellular and physiological processes to limit oxidative injury, limiting processes such as leukocyte adhesion. This review will address these aspects of the chemical biology of this multifaceted free radical and explore the beneficial effect of NO against oxidative stress.

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    • "The findings support the hypothesis that oxidative stress is another pathway in gastrointestinal mucosal injury; for instance, NO and MDA concentrations have been experimentally observed in gastric tissue after a single administration of PBZ (Martínez-Aranzales et al., 2014), and plasma concentration of those metabolites has been reported in clinical cases (El-Ashker et al., 2012). NO is involved in maintaining the integrity of gastric mucosa and is considered gastroprotective, as it regulates the production of hydrochloric acid, modulates perfusion, captures free radicals (Wink et al., 2001;Abdallah, 2010), and accelerates mucosal re-epithelialization (Li et al., 2000). Imbalance in the concentration of this metabolite in rat gastric tissue has been described after indomethacin treatment (Słomiany et al., 1999;Polat et al., 2010). "

    Full-text · Article · Jan 2016 · Revista Colombiana de Ciencias Pecuarias
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    • "Nitric oxide is generated by phagocytes and is biosynthesized endogenously from the amino acid L-arginine, oxygen, and NADPH by various nitric oxide synthase (NOS) enzymes (Palmer, Ashton, & Moncada, 1988). In addition to its signalling roles, NO@BULLET has both pro-oxidant and antioxidant activities; excessive NO@BULLET can cause direct oxidative damage, however, NO@BULLET can also scavenge circulating ROS (Joshi, Ponthier, & Lancaster, 1999; Wink et al., 2001). More importantly, O 2 • − can react directly with endothelium-derived NO@BULLET forming the harmful ONOO − molecule. "
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    ABSTRACT: Chronic obstructive pulmonary disease (COPD) is an incurable global health burden and is characterised by progressive airflow limitation and loss of lung function. In addition to the pulmonary impact of the disease, COPD patients often develop comorbid diseases such as cardiovascular disease, skeletal muscle wasting, lung cancer and osteoporosis. One key feature of COPD, yet often underappreciated, is the contribution of oxidative stress in the onset and development of the disease. Patients experience an increased burden of oxidative stress due to the combined effects of excess reactive oxygen (ROS) and nitrogen species (RNS) generation, antioxidant depletion and reduced antioxidant enzyme activity. Currently, there is a lack of effective treatments for COPD, and an even greater lack of research regarding interventions that treat both COPD and its comorbidities. Due to the involvement of oxidative stress in the pathogenesis of COPD and many of its comorbidities, a unique therapeutic opportunity arises where the treatment of a multitude of diseases may be possible with only one therapeutic target. In this review, oxidative stress and the roles of ROS/RNS in the context of COPD and comorbid cardiovascular disease, skeletal muscle wasting, lung cancer, and osteoporosis is discussed and the potential for therapeutic benefit of anti-oxidative treatment in these conditions is outlined. Because of the unique interplay between oxidative stress and these diseases, oxidative stress represents a novel target for the treatment of COPD and its comorbidities. Copyright © 2015. Published by Elsevier Inc.
    Full-text · Article · Aug 2015 · Pharmacology [?] Therapeutics
    • "The use of molecular treatments associated with the increase of NOS-3 expression and activity in CLD has shown a beneficial effect for the liver [6] [7]. In addition, the administration of antioxidants reduces the hepatotoxicity of bile acids in vitro [8] [9] [10] and in vivo [3], through the prevention of NOS-3 expression decrease and the detoxification of ROS [11]. Thus, bioreactivity of NO mitigates the effect of ROS production [12]. "
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    ABSTRACT: During the course of cholestatic liver diseases, the toxic effect of bile acids accumulation has been related to the decreased expression of endothelial nitric oxide synthase (NOS-3) and cellular oxidative stress increase. In the present study, we have investigated the relationship between these two biological events. In the human hepatocarcinoma cell line HepG2, cytotoxic response to GCDCA was characterized by the reduced activity of the respiratory complex CII/CIII, the increased expression and activation of the transcription factor Sp1, and a higher binding capacity of this at positions -1386, -632 and -104 of the NOS-3 promoter (pNOS-3). This was associated with a decreased promoter activity and a consequent reduction of NOS-3 expression. The use of antioxidants in GCDCA-treated cells caused a lower activation of Sp1 and the recovery of the pNOS-3 activity and NOS-3 expression and activity. Similarly, the specific inhibition of Sp1 resulted in the improvement of NOS-3 expression. Both, antioxidant treatment and Sp1 inhibition were associated with the reduction of cell death-related parameters. Bile duct ligation in rats confirmed in vitro results concerning the activation of Sp1 and the reduction of NOS-3 expression. Our results provide direct evidence for the involvement of Sp1 in the regulation of NOS-3 expression during cholestasis. Thus, the identification of Sp1 as a potential negative regulator of NOS-3 expression represents a new mechanism by which the accumulation of bile acids causes a cytotoxic effect through the oxidative stress increase, and provides a new potential target in cholestatic liver diseases. Copyright © 2015. Published by Elsevier Inc.
    No preview · Article · Apr 2015 · Biochemical pharmacology
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