Protective Effect Of Nitric Oxide Research Articles

The nitric oxide pathway – evidence and mechanisms for protection against liver ischaemia reperfusion injury

Ischaemia reperfusion (IR) injury is a clinical entity with a major contribution to the morbidity and mortality of liver surgery and transplantation. A central pathway of protection against IR injury utilizes nitric oxide (NO). Nitric oxide synthase (NOS) enzymes manufacture NO from L-arginine. NO generated by the endothelial NOS (eNOS) isoform protects against liver IR injury, whereas inducible NOS (iNOS)-derived NO may have either a protective or a deleterious effect during the early phase of IR injury, depending on the length of ischaemia, length of reperfusion and experimental model. In late phase hepatic IR injury, iNOS-derived NO plays a protective role. In addition to NOS consumption of L-arginine during NO synthesis, this amino acid may also be metabolized by arginase, an enzyme whose release is increased during prolonged ischaemia, and therefore diverts L-arginine away from NOS metabolism leading to a drop in the rate of NO synthesis. NO most commonly acts through the soluble guanylyl cyclase-cyclic GMP- protein kinase G pathway to ameliorate hepatic IR injury. Both endogenously generated and exogenously administered NO donors protect against liver IR injury. The beneficial effects of NO on liver IR are not, however, universal, and certain conditions, such as steatosis, may influence the protective effects of NO. In this review, the evidence for, and mechanisms of these protective actions of NO are discussed, and areas in need of further research are highlighted.

상추잎의 Paraquat 내성에 미치는 Nitric oxide의 영향

The protective effect of nitric oxide (NO) on the antioxidant system under paraquat(PQ) stress was investigated in leaves of 8-week-old lettuce (Lactuca sativa L.) plants. PQ stress caused a decrease of leaf growth including leaf length, width and weight. Application of NO donor, sodium nitroprusside (SNP), significantly alleviated PQ stress induced growth suppression. SNP permitted the survival of more green leaf tissue preventing chlorophyll content reduction and of higher quantum yield for photosystem II than in non-treated controls under PQ exposure, suggesting that NO has protective effect on chloroplast membrane in lettuce leaves. Flavonoids and anthocyanin were significantly accumulated in the leaves upon PQ exposure. However, the rapid increase of these compounds was alleviated in the SNP treated leaves. PQ treatment resulted in lipid peroxidation and induced accumulation of hydrogen peroxide (<TEX>$H_2O_2$</TEX>) in the leaves, while SNP prevented PQ induced increase in malondialdehyde (MDA) and <TEX>$H_2O_2$</TEX>. These results demonstrate that SNP serves as an antioxidant agent able to scavenge <TEX>$H_2O_2$</TEX> to protect plant cells from oxidative damage. The activities of two antioxidant enzymes that scavenge reactive oxygen species, superoxide dismutase (SOD) and catalase (CAT) in lettuce leaves in the presence of NO donor under PQ stress were higher than those under PQ stress alone. Application of 2-(4-carboxyphenyl)-4, 4, 5, 5-tetramethylimidazoline-1-oxyl-3-oxide (PTIO), a specific NO scavenger, to the lettuce leaves arrested SNP mediated protective effect on leaf growth, photosynthetic pigment and antioxidant systems. However, PTIO had little effect on lettuce leaves under PQ stress compared with that of PQ stress alone. The obtained data suggest that the damage caused by PQ stress is in part due to increased generation of active oxygen by maintaining increased antioxidant enzyme activities and SNP protects plants from oxidative stress. From these results it is suggested that NO might act as a signal in activating active oxygen scavenging system that protects plants from oxidative damage induced by PQ stress and thus confer PQ tolerance.

Morphological and physiological alterations induced by lactofen in soybean leaves are reduced with nitric oxide

Lactofen is a diphenylether herbicide recommended to control broad-leaved weeds in soybean (Glycine max) fields and its mechanism of action is the inhibition of protoporphyrinogen-IX oxidase (Protox), which acts in the chlorophyll biosynthesis. This inhibition results in an accumulation of protoporphyrin-IX, which leads to the production of reactive oxygen species (ROS) that cause oxidative stress. Consequently, spots, wrinkling and leaf burn may occur, resulting in a transitory crop growth interruption. However, nitric oxide (NO) acts as an antioxidant in direct ROS scavenging. Thus, the aim of this work was to verify, through phytometric and biochemical evaluations, the protective effect of NO in soybean plants treated with the herbicide lactofen. Soybean plants were pre-treated with different levels of sodium nitroprusside (SNP), a NO-donor substance, and then sprayed with 168 g a.i. ha-1 lactofen. Pre-treatment with SNP was beneficial because NO decreased the injury symptoms caused by lactofen in young leaflets and kept low the soluble sugar levels. Nevertheless, NO caused slower plant growth, which indicates that further studies are needed in order to elucidate the action mechanisms of NO in signaling the stress caused by lactofen in soybean crop.

NO-dependent accumulation of inorganic ions and proline determines the protective effect of nitric oxide on mustard growth under the conditions of salinization

NO-dependent accumulation of inorganic ions and proline determines the protective effect of nitric oxide on mustard growth under the conditions of salinization

Exogenous nitric oxide protects against salt-induced oxidative stress in the leaves from two genotypes of tomato (Lycopersicom esculentum Mill.)

Nitric oxide (NO) has emerged as a key molecule involved in many physiological events in plants. To characterize roles of NO in tolerance of tomato (Lycopersicom esculentum Mill.) to salt stress, the protective effects of NO against salt-induced oxidative stress in the leaves of tomato cultivar Hufan1480 (salt-tolerant) and Hufan2496 (salt-sensitive) were evaluated. Under salt stress, Hufan1480 showed higher biomass accumulation, and less oxidative damage when compared with the Hufan2496. Application of exogenous sodium nitroprusside, a NO donor, dramatically alleviated growth suppression induced by salt stress in two tomato ecotypes, reflected by decreased malondialdehyde and O 2 ·− production. Furthermore, the antioxidant enzymes superoxide dismutase, guaiacol peroxidase, catalase and ascorbate peroxidase, the antioxidant metabolites ascorbate and reduced glutathione, and the osmosis molecules proline and soluble sugar were increased in both ecotypes in the presence of NO under salt stress. Therefore, the protective effect of NO against salt-induced oxidative damages in tomato seedlings is most likely mediated through stimulation of antioxidant system.

Lacidipine has antiatherosclerotic effects independent of its actions on lipid metabolism and blood pressure

The antiatherosclerotic effect of lacidipine has been attributed to its actions on cholesterol levels, lipid metabolism or oxidant stress in advanced disease. The purpose of the present experiments was to examine whether lacidipine is protective of intimal thickening and vascular dysfunction in early atherosclerosis in the absence of the hypertension and hypercholesterolemia. A second goal was to determine whether and to what extent MMP-9 and oxidant stress are involved in possible beneficial effects of lacidipine. Lacidipine treatment (5 mg/kg/day, p.o. for 3 weeks) significantly prevented the collar-induced intimal thickening. MMP-9 expressions were increased by collar but not effected by lacidipine treatment. Nitrotyrosine staining, a marker for oxidant stress was not changed neither by collar nor lacidipine treatment in early atherosclerosis. The enhanced sensitivity to serotonine and diminished sensitivity to acetylcholine in collared arteries were restored to normal levels with treatment. These results demonstrate that the lacidipine treatment prevents the collar-induced intimal thickening and accompanying vascular dysfunction in early atherosclerosis without cholesterol loading. These beneficial effects of lacidipine were not associated with changes in either MMP-9 expression or oxidant stress. However, enhanced endothelium-dependent relaxations by lacidipine, suggest that vascular protective effects of nitric oxide may be at least partly, responsible from antiatherosclerotic effects of lacidipine.

Nitric oxide supplementation alleviates ammonium toxicity in the submerged macrophyte Hydrilla verticillata (L.f.) Royle

The likely protective effects of nitric oxide (NO) against ammonium toxicity were investigated in the submerged macrophyte Hydrilla verticillata. The plants were subjected to ammonium stress (3 mM ammonium chloride) in the presence of sodium nitroprusside (SNP, 10 μM), an NO donor. Treatment with SNP significantly increased the NO content and partially reversed the ammonium-induced negative effects, including membrane damage and the decrease in levels of chlorophyll, malondialdehyde, glutathione and ascorbic acid. Further, SNP application increased the catalytic activities of ascorbate peroxidase, superoxide dismutase, guaiacol peroxidase, catalase and glutathione S-transferase, but decreased that of NADH-oxidase. Histochemical staining showed that SNP application caused a significant decrease in the levels of superoxides and hydrogen peroxide. In contrast, application of other breakdown products of SNP (10 μM sodium ferrocyanide, 10 μM sodium nitrite and 10 μM sodium nitrate) failed to show any protective effect. The results suggest that the increased intracellular NO, resulting from SNP application, improved the antioxidant capacity of H. verticillata plants in coping with ammonium-induced oxidative stress.

Nitric oxide alleviates lipid peroxidation induced by osmotic stress during senescence of detached leaves of Malus hupehensis Rehd.

SummaryThe protective effect of nitric oxide (NO) against membrane lipid peroxidation induced by polyethylene glycol (PEG) osmotic stress was investigated in relation to the metabolism of reactive oxygen species (ROS) and proline accumulation during the senescence of detached leaves of Malus hupehensis Rehd. in the dark. Membrane lipid peroxidation was determined by measuring the increase in malondialdehyde (MDA) content. PEG-induced osmotic stress resulted in a marked increase in the contents of MDA and proline, as well as the activities of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX). Sodium nitroprusside (SNP), a donor of NO, prevented the PEG-induced increase in MDA content, but, with an increase in proline content as well as increases in the activities of CAT and APX, and in the levels of superoxide anions and hydrogen peroxide (H2O2).Treatment with SNP alone also alleviated lipid peroxidation, compared to water-treated leaves, with an increased proline content and SOD activity, but decreased the levels of superoxide anions and H2O2. We concluded that NO was effective at alleviating membrane lipid peroxidation induced by osmotic stress (PEG) during the senescence of detached leaves of M. hupehensis Rehd., suggesting a similar role for NO as in the regulation of ROS-dependent lipid peroxidation in animals. The relationships between NO-mediated regulation of lipid peroxidation and ROS metabolism, as well as proline accumulation, are discussed.

Protective effect of nitric oxide on light-induced oxidative damage in leaves of tall fescue

Nitric oxide (NO) is an important signaling molecule involved in many physiological processes. In this study, the effect of NO on oxidative damage caused by high levels of light was investigated in leaves of two varieties of tall fescue (Arid3 and Houndog5). Leaves of Houndog5 were more susceptible to high-light stress than Arid3 leaves. Pretreatment of these leaves with NO donor sodium nitroprusside (SNP), prior to exposure to high-light stress, resulted in reduced light-induced electrolyte leakage and reduced contents of malondialdehyde, hydrogen peroxide (H 2O 2) and superoxide radicals (O 2 •−). The activities of superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX) and glutathione reductase (GR) increased in both varieties in the presence of SNP under high-light stress, but lipoxygenase (LOX) activity was inhibited. These responses could be reversed by pretreatment with the NO scavenger 2-(4-carboxy-2-phenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (PTIO). A pronounced increase in nitric oxide synthase (NOS) activity and NO release was found in light-tolerant Arid3 plants after exposure to high-light stress, while only a small increase was observed in more sensitive Houndog5. Pretreatment with the NOS inhibitor N ω-nitro- l-arginine (LNNA) resulted in increased oxidative damage under high-light stress, with more injuries occurring in Arid3 than Houndog5. These results suggest that high-light stress induced increased NOS activity leading to elevated NO. This NO might act as a signaling molecule triggering enhanced activities of antioxidant enzymes, further protecting against injuries caused by high intensity light. This protective mechanism was found to more efficiently acclimate light-tolerant Arid3 than light-sensitive Houndog5.

Interaction of nitric oxide with the activity of cytosolic NADH/cytochrome c electron transport system

Nitric oxide ( NO) generated by the dissociation of S-nitrosoglutathione or added as gaseous solution, inhibits the oxidation of exogenous NADH supported by the activity of the cytosolic NADH/cyto-c electron transport pathway. The inhibition is immediate, very strong, higher at lower oxygen concentration, independent on the NO concentration and remains constant as long as NO is no more available and then is spontaneously removed. The data obtained, not in contrast with those reported with isolated cytochrome oxidase (Cox), strengthen a new concept: reduced cytochrome c (cyto-c) and NO behave as two substrates of Cox, which promotes their oxidation with molecular oxygen as a co-substrate. In the presence of NO, Cox exhibits the property of switching from cyto-c oxidase to NO oxidase activity. With an “all or nothing” process Cox becomes an efficient NO scavenger. The persistence of membrane potential, even in the presence of high inhibition of oxygen uptake, could be tentatively correlated to the protective effect of NO on the ischaemic–reperfusion injury.

Neuronal nitric oxide synthase in heart mitochondria: a matter of life or death

Neuronal nitric oxide synthase in heart mitochondria: a matter of life or death

Protective effect of nitric oxide on cytoskeletal proteins in rat soleus under eccentric exercise

An in vivo study was performed to see whether deterioration of the muscle cytoskeleton caused by eccentric exercise could be counteracted by raising the tissue content of nitric oxide. In Wistar rats that ran downhill on a treadmill inclined at 16° for 40 min at 20 m/min, the desmin content in m. soleus measured 24 h later declined by 15%, and the percentage of ruptures in the dystrophin layer was three times higher than in the control. Destruction of cytoskeletal proteins was also pronounced in rats pretreated with a blocker of NO synthase before exercise. By contrast, animals that received a nitric oxide donor (L-arginine) prior to running had control levels of desmin and dystrophin. It was concluded that nitric oxide can protect muscle cytoskeletal proteins in a single eccentric exercise.

Establishment of ischemic precondition model and the protective effect of nitric oxide on PC12 cell line

Objective To establish the ischemic precondition ([PC) model of PC12 cell line in vitro, and to explore the effect of nitric oxide (NO) on the IPC cerebral protection. Method PC12 cells were cultured and used for producing the model of ischemie precondition by the way of oxygen-glucose deprivation. Twenty dishes of cells were randomly divided into four groups (5 dishes for each group): control group, ischemic precondition group (IPC),non-ischemic precondition group (NIPC) and L-NAME treatment group (L-NAME). In control group, the cells were in-cubated with low glucose (<1 g/L) and2% FBS medium in normal oxygen; in IPC group, the cells were administrated with oxygen-glucose deprivation (OGD) for 6 hours, and then subjected with reperfuaion before OGD 15 hours; in NIPC group, the cells were treated the same as control group for 6 hours, and then subjected with reperfusion before OGD 15 hours; in L-NAME group, the cells received L-NAME (1 mmol/L) and cocultured for 30 minutes before OGD 6 hours, and then received the same treatment as the IPC group. To test whether the model was established, metabolic rate of MIT, LDH release were measured and the apoptosis rate was detected by flow cytometry following oxygen-glucose deprivation 15 hours. The activity of nitric oxide synthases (NOS) was as-sessed by biochemical assay. One-way ANOVA and LSD multiple comparison test were used to analyze differences among different groups, and P<0.05 was considered different. Results Compared with NIPC group, the metabolic rate of MTT increased (94.9%±35.1%, P<0.05), while LDH release and the cell apoptotic rate decreased significantly in IPC group (279.1%±28.1%, P<0.03). Compared with control group(100.0%± 13.5%),the activities of NOS increased both in NIPC and IPC groups (390.0%±14.6%, P<0.01;126.3% ±10.6%, P<0.01). Moreover, the apoptosis rates in each group (control group, IPC group, NIPC group and L-NAME group) were 5.90, 8.73, 38.62 and 11.73%,respectively. Conclusions IPC reduces the death and apoptosis rate of PC12 cell after oxygen-glucose deprivation injury. NO might be involved, but it is not the only factor. Key words: Ischemic precondition; Nitric oxide; b-NAME; PC12 cell line

Effect of Chronic Inhibition of Nitric Oxide on Hypertension, Insulin Resistance, and Cardiovascular Remodeling in Glucose-fed Rats

To determine the contribution of nitric oxide (NO) in cardiovascular remodeling associated to hypertension and insulin resistance, male Sprague-Dawley rats received tap water supplemented or not (control), with 10% D-glucose (G) and/or 50 mg x kg(-1) x d(-1) L-NAME to inhibit NO synthase (G-LN or LN) for 4 weeks. Systolic blood pressure increased by 12%, 26%, and 39% with G, LN, and G-LN treatments, respectively. Hyperinsulinemia and insulin resistance (homeostasis model assessment index) occurred in G-treated rats (P < 0.05) and were further increased in G-LN (P < 0.01). Plasma adrenaline concentrations were markedly increased in all treated groups, especially in G-LN (P < 0.01), whereas noradrenaline was increased in G-treated rats only. Whereas no cardiac hypertrophy or fibrosis was detected, aortic hypertrophy occurred in LN and G-LN rats (P < 0.001) without smooth muscle hyperplasia. Superoxide anion formation was increased in the aorta of all treated groups (P < 0.01) and in the heart of LN (P < 0.05), but reduced nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase activity was not affected. In conclusion, the loss of the wide-range protective effects of NO, the increased vascular oxidative stress, and the sympathoadrenal hyperactivity are among the contributing factors leading to the exacerbation of hypertension and insulin resistance in G-LN. These factors were sufficient to cause vascular but not cardiac hypertrophy.

Protective Effect of Nitric Oxide against Oxidative Damage in Arabidopsis Leaves under Ultraviolet-B Irradiation

Nitric oxide (NO) is a key molecule involved in many physiological processes. To characterize its roles in the tolerance of Arabidopsis thaliana to ultraviolet-B (UV-B), we investigated the effect of a reduced endogenous NO level on oxidative damage to wild-type and mutant (Atnoa1) plants. Under irradiation, hydrogen peroxide was accumulated more in mutant leaves than in the wild type. However, the amounts of UV-B-absorbing compounds (flavonoids and anthocyanin) and the activities of two antioxidant enzymes—catalase (CAT, EC 1.11.1.6) and ascorbate peroxidase (APX, EC 1.11.1.11)—were lower in leaves of the former. Supplementing with sodium nitroprusside, an NO donor, could alleviate the oxidative damage to mutant leaves by increasing flavonoid and anthocyanin contents and enzyme activities. In comparison, $${\text{N}}^{\text{ $ \omega $ }} - {\text{nitro}} - l - {\text{arginine}}$$ , an inhibitor of nitric oxide synthase, had the opposite effects on oxidation resistance in wild-type leaves. All these results suggest that nitric oxide acts as a signal for an active oxygen-scavenging system that protects plants from oxidative stress induced by UV-B irradiation.

Nitric Oxide Mechanism of Protection in Ischemia and Reperfusion Injury

In 1992 nitric oxide (NO) was declared molecule of the year by Science magazine, and ever since research on this molecule continues to increase. Following this award, NO was shown to be a mediator/protector of ischemia and reperfusion injury in many organs, such as the heart, liver, lungs, and kidneys. Controversy has existed concerning the actual protective effects of NO. However, literature from the past 15 years seems to reinforce the consensus that NO is indeed protective. Some of the protective actions of NO in ischemia and reperfusion are due to its potential as an antioxidant and anti-inflammatory agent, along with its beneficial effects on cell signaling and inhibition of nuclear proteins, such as NF-κ B and AP-1. New therapeutic potentials for this drug are also continuously emerging. Exogenous NO and endogenous NO may both play protective roles during ischemia and reperfusion injury. Sodium nitroprusside and nitroglycerin have been used clinically with much success; though only recently have they been tested and proven effective in attenuating some of the injuries associated with ischemia and reperfusion. NO inhalation has, in the past, mostly been used for its pulmonary effects, but has also recently been shown to be protective in other organs. The potential of NO in the treatment of ischemic disease is only just being realized. Elucidation of the mechanism by which NO exerts its protective effects needs further investigation. Therefore, this paper will focus on the mechanistic actions of NO in ischemia and reperfusion injury, along with the compound's potential therapeutic benefits.

Nitric oxide utilizes NF-κB to signal its neuroprotective effect against alcohol toxicity

Alcohol damages the developing brain and can lead to fetal alcohol syndrome. One of alcohol's most important neuropathologic effects is neuronal death. As neurons mature, they become less vulnerable to alcohol-induced death because they acquire a protective signaling pathway, mediated by nitric oxide (NO). This pathway is the NO–cGMP–cyclic GMP-dependent protein kinase G (NO–cGMP–PKG) pathway. The goal of the present studies was to determine whether nuclear factor kappa B (NF-κB) is the downstream effector through which the NO–cGMP–PKG pathway signals its neuroprotective effects against alcohol. An activator of NF-κB, tumor necrosis factor-alpha (TNF-α), protected immature cerebellar granule neuron cultures against alcohol-induced cell death in a dose-dependent fashion. The protective effect of TNF-α was similar in magnitude to the protective effects of NMDA and DETA-NONOate, both of which are NO–cGMP–PKG pathway activators. Blockade of the pathway at its first step with NAME, second step with LY83583, or third step with PKG inhibitor increased alcohol-induced cell death and the vulnerability of mature neurons to alcohol toxicity. TNF-α protected the neurons, even when the NO–cGMP–PKG pathway was blocked at upstream sites. NF-κB activation inhibitor (NFi) worsened alcohol-induced cell death and blocked the protective effects of NO–cGMP–PKG pathway activators and TNF-α. TNF-α reduced the alcohol vulnerability of immature neurons, while NFi increased the vulnerability of mature neurons. Both NMDA and TNF-α led to the phosphorylation and degradation of IκBα, demonstrating that both agents can activate NF-κB in cerebellar granule cells. Thus, NF-κB plays a critical role in the acquisition of alcohol resistance by maturing neurons and is a key downstream effector through which the NO–cGMP–PKG pathway signals its neuroprotective effects against alcohol.

The effects of NOS2 gene deletion on mice expressing mutated human AbetaPP.

Nitric oxide synthase 2 (NOS2) and its gene product, inducible NOS (iNOS) play an important role in neuroinflammation by generating nitric oxide (NO), a critical signaling and redox factor in the brain. Although NO is associated with tissue damage, it can also promote cell survival. We hypothesize that during long-term exposure to amyloid-beta (Abeta) in Alzheimer's disease (AD), NO levels fall in the brain to a threshold at which the protective effects of NO cannot be sustained, promoting Abeta mediated damage. Two new mouse models of AD have been developed that utilize this concept of NO's action. These mice express human amyloid-beta protein precursor (AbetaPP) mutations that generate Abeta peptides on a mouse NOS2 knockout background. The APP/NOS2(-/-) bigenic mice progress from Abeta production and amyloid deposition to hyperphosphorylated normal mouse tau at AD-associated epitopes, aggregation and redistribution of tau to somatodendritic regions of neurons and significant neuronal loss including loss of interneurons. This AD-like pathology is accompanied by robust behavioral changes. As APP/NOS2(-/-) bigenic mice more fully model the human AD disease pathology, they may serve as a tool to better understand disease progression in AD and the role of NO in altering chronic neurological disease processes.

Novel soluble guanylyl cyclase stimulator BAY 41-2272 attenuates ischemia-reperfusion-induced lung injury

The protective effects of nitric oxide (NO), a physiological activator of soluble guanylyl cyclase (sGC), have been reported in ischemia-reperfusion (I/R) syndrome of the lung. Therefore, we studied the effects of BAY 41-2272, a novel sGC stimulator, on I/R injury of the lung in an isolated intact organ model. Lung injury was assessed by measuring weight gain and microvascular permeability (capillary filtration coefficient, K(fc)). Release of reactive oxygen species (ROS) into the perfusate was measured during early reperfusion by electron spin resonance (ESR) spectroscopy. Rabbit lungs were treated with BAY 41-2272, N(G)-monomethyl-L-arginine (L-NMMA), or NO to evaluate the effects on I/R-induced lung injury. In untreated lungs, a dramatic rise in K(fc) values and weight gain during reperfusion were observed, and these results were associated with increased ROS production. Both, BAY 41-2272 and L-NMMA significantly attenuated vascular leakage and suppressed ROS release. Additional experiments showed that BAY 41-2272 diminished PMA-induced ROS production by NADPH oxidase. A pharmacological inhibition of the enzyme with consequent reduction in ROS levels decreased I/R injury. NO had only marginal effect on I/R injury. Thus BAY 41-2272 protects against I/R-induced lung injury by interfering with the activation of NADPH oxidases.

Osteoarthritis and nitric oxide

Osteoarthritis (OA) is caused by both biochemical and mechanical factors. While the mechanisms that underlie the disease are not completely understood, investigators have characterized a number of catabolic and protective factors that have a role in the disease process. Nitric oxide (NO) and its redox derivatives appear to have a number of different functions in both normal and pathophysiological joint conditions. Until recently, NO was considered a catabolic factor that was responsible for perpetuating the OA disease process by mediating the expression of proinflammatory cytokines, inhibiting the synthesis of collagen and proteoglycans and inducing apoptosis. However, recent studies suggest that NO and its redox derivatives may also have protective effects on cartilage. This review will summarize the literature on the effects of NO on cartilage and chondrocytes as well as discuss some evidence that suggests potential protective effects of NO and/or its derivatives on other cell types. More research is needed to elucidate the role of NO and its derivatives on both normal and osteoarthritis cartilage.