Procyanidins extracted from pine bark protect α‐tocopherol in ECV 304 endothelial cells challenged by activated RAW 264.7 macrophages: role of nitric oxide and peroxynitrite

Virgili, Fabio; Kim, Doran; Packer, Lester

doi:10.1016/s0014-5793(98)00778-9

Cited by 72 publications

(32 citation statements)

References 23 publications

(25 reference statements)

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“…It is also important to note that a number of studies have analyzed the response of human cells to murine RAW 264.7 cells, with results that frequently replicate key features of disease pathology. [85][86][87][88][89][90][91][92][93] Future studies will use primary human macrophages to further develop this coculture system. Eventual testing of new therapeutics, particularly those targeting macrophage activation, using our developed coculture system will also be a key focus of future work.…”

Section: Discussionmentioning

confidence: 99%

A Three-Dimensional Chondrocyte-Macrophage Coculture System to Probe Inflammation in Experimental Osteoarthritis

Samavedi

Díaz‐Rodríguez

Erndt-Marino

et al. 2017

Tissue Engineering Part A

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The goal of the present study was to develop a fully three-dimensional (3D) coculture system that would allow for systematic evaluation of the interplay between activated macrophages (AMs) and chondrocytes in osteoarthritic disease progression and treatment. Toward this end, our coculture system was first validated against existing in vitro osteoarthritis models, which have generally cultured healthy normal chondrocytes (NCs)-in two-dimensional (2D) or 3D-with proinflammatory AMs in 2D. In this work, NCs and AMs were both encapsulated within poly(ethylene glycol) diacrylate hydrogels to mimic the native 3D environments of both cell types within the osteoarthritic joint. As with previous studies, increases in matrix metalloproteinases (MMPs) and proinflammatory cytokines associated with the early stages of osteoarthritis were observed during NC-AM coculture, as were decreases in protein-level Aggrecan and collagen II. Thereafter, the coculture system was extended to osteoarthritic chondrocytes (OACs) and AMs to evaluate the potential effects of AMs on pre-existing osteoarthritic phenotypes. OACs in coculture with AMs expressed significantly higher levels of MMP-1, MMP-3, MMP-9, MMP-13, IL-1b, TNF-a, IL-6, IL-8, and IFN-g compared to OACs in mono-culture, indicating that proinflammatory macrophages may intensify the abnormal matrix degradation and cytokine secretion already associated with OACs. Likewise, AMs cocultured with OACs expressed significantly more IL-1b and VEGF-A compared to AM mono-culture controls, suggesting that OACs may intensify abnormal macrophage activation. Finally, OACs cultured in the presence of nonactivated macrophages produced lower levels of MMP-9 and proinflammatory cytokines IL-1b, TNF-a, and IFN-g compared to OACs in the OAC-AM system, results that are consistent with anti-inflammatory agents temporarily reducing certain OA symptoms. In summary, the 3D coculture system developed herein captures several key features of inflammatory OA and may prove useful in future screening of therapeutic agents and/or assessment of disease progression mechanisms.

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Section: Discussionmentioning

confidence: 99%

A Three-Dimensional Chondrocyte-Macrophage Coculture System to Probe Inflammation in Experimental Osteoarthritis

Samavedi

Díaz‐Rodríguez

Erndt-Marino

et al. 2017

Tissue Engineering Part A

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“…␤-Carotene, for instance, can scavenge free radicals at low oxygen tension, but acts as a prooxidant at higher oxygen tension [61]. Likewise, pycnogenol inhibits the inducible nitric oxide synthase at high doses, but stimulates it at low doses [62,63]. Other concentration-dependent effects may yet be discovered.…”

Section: Discussionmentioning

confidence: 99%

“…However, ␣-lipoic acid is thought to spare nitric oxide [70], which helps keep peripheral blood vessels dilated. Furthermore, pycnogenol prolongs the life of ascorbate radical [21], which also scavenges free radicals and protects vitamin E [63]. Pycnogenol also modulates the activity of certain transcription factors, especially nuclear factor-B [71][72][73], and inhibits the activity of certain kinases [74], both of which could modulate signal-transduction pathways to regulate the activity of cells.…”

Section: Discussionmentioning

confidence: 99%

Influence of treatment of diabetic rats with combinations of pycnogenol, ?-carotene, and ?-lipoic acid on parameters of oxidative stress

Berryman

Maritim

Sanders

et al. 2005

J. Biochem. Mol. Toxicol.

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Treatment with antioxidants may act more effectively to alter markers of free radical damage in combinations than singly. This study has determined whether treatment with combinations of pycnogenol, beta-carotene, and alpha-lipoic acid was more effective at reducing oxidative stress in diabetic rats than treatment with these antioxidants alone. It is not feasible, based on this study, to assume that there are interactive effects that make combinations of these antioxidants more effective than any one alone to combat oxidative stress. Female Sprague-Dawley rats, normal and streptozotocin-induced diabetic, were treated (10 mg/kg/day ip for 14 days) with pycnogenol, beta-carotene, pycnogenol + beta-carotene, or pycnogenol + beta-carotene + alpha-lipoic acid; controls were untreated. Concentrations of thiobarbituric acid reactive substances, glutathione and glutathione disulfide, and activities of glutathione reductase, glutathione peroxidase, superoxide dismutase, and catalase were measured in liver, kidney, and heart. Four types of effects were observed: (1) treatment with beta-carotene alone either reversed (cardiac glutathione disulfide) or elevated (cardiac glutathione, hepatic glutathione peroxidase activity) levels seen in diabetic animals; (2) beta-carotene alone produced no effect, but pycnogenol both alone and in combinations elevated (renal glutathione peroxidase and glutathione reductase activities, hepatic glutathione reductase activity and glutathione disulfide) or depressed (cardiac glutathione disulfide) levels seen in untreated diabetic animals; (3) all treatments with antioxidants, either alone or in combination, either normalized (lipid peroxidation in all tissues), elevated (hepatic GSH, cardiac glutathione peroxidase activity), or had no effect on (activities of hepatic catalase and superoxide dismutase in all tissues) levels seen in diabetic animals; (4) in only one case (cardiac glutathione reductase activity) levels in diabetic animals treated with combinations of antioxidants were normal, but elevated in animals treated with either antioxidant alone. Antioxidant effects seem to be dependent on the nature of the antioxidant used and not on combination effects.

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“…Interest is increasing in the protective biological effects of some natural antioxidants, especially from edible plants, which are candidates for preventing various inflammatory disorders and extending the life span of humans (Unno et al 1997;Yang et. al 1998;Virgili et al 1998;Wakabayashi 1999). Many of the natural antioxidants reported in the literature are related to the polyphenol or flavonoid families having potent antioxidant properties including the scavenging of oxygen radicals, nitric oxide and lipid radicals (Nowak et al 1993).…”

Section: Discussionmentioning

confidence: 99%

Effects of Apocynin and Natural Antioxidant from Spinach on Inducible Nitric Oxide Synthase and Cyclooxygenase‐2 Induction in Lipopolysaccharide‐Induced Hepatic Injury in Rat

Lomnitski

Foley

Grossman

et al. 2000

Pharmacology & Toxicology

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Abstract:The immunoreactivity of inducible nitric oxide synthase, and cyclooxygenase-2 was compared among groups of male Wistar rats comprising those injected with lipopolysaccharide following pretreatment with either natural antioxidant from spinach or the antioxidant apocynin, with lipopolysaccharide without pretreatment with antioxidants, with each of the two antioxidants alone, and untreated controls. The grade of staining of both inducible nitric oxide synthase and cyclooxygenase-2 increased with the severity of the inflammatory reaction in the lipopolysaccharide-treated animals, compared to the antioxidant-treated groups. Interpretation of the results of the immunostained tissues indicated that pretreatment with either antioxidant significantly (P∞0.05) attenuated the lipopolysaccharide-stimulated inducible nitric oxide synthase induction. Analysis of the cycloxygenase-2-stained liver samples indicated that the pretreatment with the natural antioxidant NAO significantly (P∞0.05) attenuated lipopolysaccharide-stimulated cycloxygenase-2 induction; whereas, in animals pretreated with apocynin, there was a trend of reduction in the cyclooxygenase-2 expression, but not statistically significant (P±0.05). The negative nitrotyrosine immunoreactivity of the lipopolysaccharide-related hepatic lesions may indicate that there was relatively low interaction between superoxide anions and nitric oxide to form peroxynitrite or that the expression levels of the nitrotyrosine were below the limit of detection. In all treatment groups a positive correlation (P∞0. 05, rΩ0.86) found between the inducible nitric oxide synthase and cyclooxygenase-2 scores suggests a strong relationship between these two parameters. The results indicate the possible therapeutic efficacy of NAO and apocynin in the prevention of liver damage related to clinical endotoxemia known to be associated with oxidative stress.

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Procyanidins extracted from pine bark protect α‐tocopherol in ECV 304 endothelial cells challenged by activated RAW 264.7 macrophages: role of nitric oxide and peroxynitrite

Cited by 72 publications

References 23 publications

A Three-Dimensional Chondrocyte-Macrophage Coculture System to Probe Inflammation in Experimental Osteoarthritis

A Three-Dimensional Chondrocyte-Macrophage Coculture System to Probe Inflammation in Experimental Osteoarthritis

Influence of treatment of diabetic rats with combinations of pycnogenol, ?-carotene, and ?-lipoic acid on parameters of oxidative stress

Effects of Apocynin and Natural Antioxidant from Spinach on Inducible Nitric Oxide Synthase and Cyclooxygenase‐2 Induction in Lipopolysaccharide‐Induced Hepatic Injury in Rat

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