Nitric oxide protects against cellular damage and cytotoxicity from reactive oxygen species.

Abstract

Nitric oxide, NO, which is generated by various components of the immune system, has been presumed to be cytotoxic. However, NO has been proposed to be protective against cellular damage resulting during ischemia reperfusion. Along with NO there is often concomitant formation of superoxide/hydrogen peroxide, and hence a synergistic relationship between the cytotoxic effects of nitric oxide and these active oxygen species is frequently assumed. To study more peroxide or to hypoxanthine/xanthine oxidase resulted in the degradation of the dopamine uptake and release mechanism. As was observed in the case of the V79 cells, the presence of NO essentially abrogated this peroxide-mediated cytotoxic effect on mesencephalic cells.Nitric oxide, NO, is one of the proposed cytotoxic species produced by the immune surveillance system (1, 2). Many reports also suggest that during the ischemia reperfusion event, NO mediates tissue injury (3)(4)(5)(6)(7)(8)(9)(10)(11)(12). However, it has been suggested that NO can function as a protective agent on the basis of two lines of evidence: (i) NO synthase (NOS) inhibitors increase tissue damage during in vivo ischemia reperfusion within the cerebral cortex, and (ii) in more direct evidence, NO has been shown to prevent damage during ischemia reperfusion events in both brain and heart (13-18). Additional studies provide evidence that NO, though present, plays a minimal role in the pathological effects associated with ischemia reperfusion injury (19,20) or tumor necrosing factor-mediated cytotoxicity (21). Unfortunately, the exact role(s) NO plays in cytotoxicity in vivo is not clear because there are a number of different physiological functions NO or the NOS inhibitors could affect simultaneously. It has been proposed that NO or reactive nitrogen oxide species can directly cause cell death. However, primary neuronal cell cultures exposed to concentrations of NO as high as 1 mM show no adverse effects (22, 23). Many of the biological events in which NO has been proposed as a toxin occur concurrently with the production of reactive oxygen species-e.g., immune response and ischemia reperfusion injury.To clarify the relationship between the cytotoxic properties of the reactive oxygen species and NO, it is necessary to simplify the system. We now show that NO released from a series of compounds known as the "NONOates" (24) Abstract Service Registry Number 136587-13-8) were synthesized and assayed for NO production via chemiluminescence technique as described (24).Enzyme Analysis/Controls. The activity of XO was monitored in the absence and presence of 1 mM DEA/NO by two different assays. (i) Superoxide-induced reduction of ferricytochrome c to ferrocytochrome c was monitored spectrophotometrically at 550 nm (25). The reaction was carried out in a 1-ml volume in aerated 50 mM phosphate buffer (pH 7.8) containing 50 ,AM diethylenetriaminepentaacetic acid. HX was maintained at 2.5 mM and ferricytochrome c at 20 ,uM. The reactions were initiated with the addition of XO (final con...

Nitric oxide modulates murine yolk sac vasculogenesis and rescues glucose induced vasculopathy

“…2001; Wink et al, 1993). Accordingly, we showed that NO supplementation to hyperglycemic media reduces hyperglycemia-induced ROS.…”

“…Studies using low doses of NO donors demonstrated that NO directly acts as an antioxidant (Chang et al, 1996;Joshi et al, 1999;Kim et al, 1995;Wink et al, 1993). Therefore, we hypothesized that the vasculopathy induced by L-NMMA may be due to increased ROS, suggesting a common pathway with hyperglycemia.…”

Interactive role of nitric oxide and superoxide anion in neutrophil-mediated endothelial cell injury

“…The former effect is attributed to the formation of the toxic peroxynitrite after reaction with O 2 Ϫ [11]. The latter effect is not well defined, although inhibition of oxidative killing of Chinese hamster V79 cells [27], attenuation of low-density lipoprotein oxidation [28], and prevention of myocardial ischemiareperfusion injury [10] have been demonstrated. Our goal was to understand the interactive role of NO and ROI in cellular events that culminate in PMN-mediated EC injury.…”

Nitric oxide protects endothelial cells from tumor necrosis factor‐α‐mediated cytotoxicity: possible involvement of cyclic GMP

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