scholarly journals Antioxidants and fatty acids in the amelioration of rheumatoid arthritis and related disorders

2001 ◽  
Vol 85 (3) ◽  
pp. 251-269 ◽  
Author(s):  
L. Gail Darlington ◽  
Trevor W. Stone
Keyword(s):  
Rheumatoid Arthritis ◽  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Fatty Acids ◽  
Free Radicals ◽  
Nitric Oxide Synthase ◽  
Prostaglandin E ◽  
Oxygen Species ◽  
Beneficial Effects ◽  
Oxide Synthase

The generation of reactive oxygen species (free radicals) is an important factor in the development and maintenance of rheumatoid arthritis in humans and animal models. One source of free radicals is nitric oxide produced within the synoviocytes and chondrocytes and giving rise to the highly toxic radical peroxynitrite. Several cytokines, including tumour necrosis factor-α (TNFα) are involved in the formation of free radicals, partly by increasing the activity of nitric oxide synthase. Indeed, nitric oxide may mediate some of the deleterious effects of cytokines on bone resorption. Aspirin, tetracyclines, steroids and methotrexate can suppress nitric oxide synthase. Dietary antioxidants include ascorbate and the tocopherols and beneficial effects of high doses have been reported especially in osteoarthritis. There is also evidence for beneficial effects of β-carotene and selenium, the latter being a component of the antioxidant enzyme glutathione peroxidase. The polyunsaturated fatty acids (PUFA) include then-3 compounds, some of which are precursors of eicosanoid synthesis, and then-6 group which can increase formation of the pro-inflammatory cytokines TNFα and interleukin-6, and of reactive oxygen species. Some prostaglandins, however, suppress cytokine formation, so thatn-3 PUFA often oppose the inflammatory effects of somen-6-PUFA. γ-linolenic acid (GLA) is a precursor of prostaglandin E1, a fact which may account for its reported ability to ameliorate arthritic symptoms. Fish oil supplements, rich inn-3 PUFA such as eicosapentaenoic acid have been claimed as beneficial in rheumatoid arthritis, possibly by suppression of the immune system and its cytokine repertoire. Some other oils of marine origin (e.g. from the green-lipped mussel) and a range of vegetable oils (e.g. olive oil and evening primrose oil) have indirect anti-inflammatory actions, probably mediated via prostaglandin E1. Overall, there is a growing scientific rationale for the use of dietary supplements as adjuncts in the treatment of inflammatory disorders such as rheumatoid arthritis and osteoarthritis.

Induction of inducible nitric oxide synthase increases the production of reactive oxygen species in RAW264.7 macrophages

2010 ◽  
Vol 30 (4) ◽  
pp. 233-241 ◽  
Author(s):  
Kai Zhao ◽  
Zhen Huang ◽  
Hongling Lu ◽  
Juefei Zhou ◽  
Taotao Wei
Keyword(s):  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Nitric Oxide Synthase ◽  
Reactive Oxygen ◽  
Inos Expression ◽  
Raw264.7 Cells ◽  
Ros Production ◽  
Oxygen Species ◽  
Raw264.7 Macrophages ◽  
Oxide Synthase

Macrophages produce a large volume of ROS (reactive oxygen species) through respiratory burst. However, the influence of iNOS [inducible NOS (nitric oxide synthase)] activation on ROS production remains unclear. In the present study, the kinetic generation of ROS in RAW264.7 murine macrophages was monitored by chemiluminescence. PMA induces a robust chemiluminescence in RAW264.7 cells, suggesting PKC (protein kinase C)-related assembly and activation of NOX (NADPH oxidase). The effects of iNOS induction on ROS production were examined. Induction of iNOS expression in RAW264.7 cells with LPS (lipopolysaccharide; 1 μg/ml) causes a significant increase in PMA-induced chemiluminescence, which could be enhanced by the NOS substrate, L-arginine, and could be abolished by the NOS inhibitor, L-NNA (NG-nitro-L-arginine). Further experiments reveal that induction of iNOS expression enhances the PMA-stimulated phosphorylation of the p47phox subunit of NOX, and promotes the relocalization of cytosolic p47phox and p67phox subunits to the membrane. Inhibition of PKCζ by its myristoylated pseudosubstrate significantly decreased the PMA-stimulated phosphorylation of the p47phox in LPS-pretreated cells, suggesting that PKCζ is involved in the iNOS-dependent assembly and activation of NOX. Taken together, the present study suggests that the induction of iNOS upregulates the PMA-induced assembly of NOX and leads to the enhanced production of ROS via a PKCζ-dependent mechanism.

scholarly journals Insulin-Induced Generation of Reactive Oxygen Species and Uncoupling of Nitric Oxide Synthase Underlie the Cerebrovascular Insulin Resistance in Obese Rats

2012 ◽  
Vol 32 (5) ◽  
pp. 792-804 ◽  
Author(s):  
Prasad VG Katakam ◽  
James A Snipes ◽  
Mesia M Steed ◽  
David W Busija
Keyword(s):  
Nitric Oxide ◽  
Insulin Resistance ◽  
Reactive Oxygen Species ◽  
Nitric Oxide Synthase ◽  
Cerebral Arteries ◽  
Reactive Oxygen ◽  
Ros Generation ◽  
Oxygen Species ◽  
Fluorescence Studies ◽  
Oxide Synthase

Hyperinsulinemia accompanying insulin resistance (IR) is an independent risk factor for stroke. The objective is to examine the cerebrovascular actions of insulin in Zucker obese (ZO) rats with IR and Zucker lean (ZL) control rats. Diameter measurements of cerebral arteries showed diminished insulin-induced vasodilation in ZO compared with ZL. Endothelial denudation revealed vasoconstriction to insulin that was greater in ZO compared with ZL. Nonspecific inhibition of nitric oxide synthase (NOS) paradoxically improved vasodilation in ZO. Scavenging of reactive oxygen species (ROS), supplementation of tetrahydrobiopterin (BH4) precursor, and inhibition of neuronal NOS or NADPH oxidase or cyclooxygenase (COX) improved insulin-induced vasodilation in ZO. Immunoblot experiments revealed that insulin-induced phosphorylation of Akt, endothelial NOS, and expression of GTP cyclohydrolase-I (GTP-CH) were diminished, but phosphorylation of PKC and ERK was enhanced in ZO arteries. Fluorescence studies showed increased ROS in ZO arteries in response to insulin that was sensitive to NOS inhibition and BH4 supplementation. Thus, a vicious cycle of abnormal insulin-induced ROS generation instigating NOS uncoupling leading to further ROS production underlies the cerebrovascular IR in ZO rats. In addition, decreased bioavailability and impaired synthesis of BH4 by GTP-CH induced by insulin promoted NOS uncoupling.

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