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Grape skin extract reduced pulmonary oxidative response in mice exposed to cigarette smoke.

Pires KM, Valença SS, Resende ÂC, Porto LC, Queiroz EF, Moreira DD, de Moura RS - Med. Sci. Monit. (2011)

Bottom Line: In addition, we used a separate group treated with NG-nitro-L-arginine methyl ester (an NO inhibitor) to confirm nitric oxide (NO) involvement in GSE effects.This is associated with decreased MMP-9 activity, decreased number of inflammatory cells in the bronchoalveolar lavage fluid, and reduced levels of lipid peroxidation.Our results indicate that beneficial effects of GSE are NO-dependent.

View Article: PubMed Central - PubMed

Affiliation: Inflammation, Oxidative Stress and Cancer Laboratory - ICB/CCS/Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.

ABSTRACT

Background: Oxidative stress has been implicated in the pathogenesis and progression of chronic obstructive pulmonary disease (COPD), and cigarette smoke (CS) is known to be one of the major sources of oxidants in the lungs. We postulated that acute administration of GSE (grape skin extract) would either reduce or protect the ALI (acute lung inflammation) produced by CS via NO release.

Material/methods: We adopted a nutritional approach by investigating the inflammatory cells, metalloproteinase 9 (MMP-9) activity, and oxidative stress markers (superoxide dismutase - SOD; catalase - CAT; glutathione peroxidase (GPx) activities and malondialdehyde - MDA - levels) that play a role in the development of acute lung inflammation (ALI). Therefore, we tested an orally active antioxidant produced from grape skin manipulation (grape skin extract - GSE), in mice exposed to CS from 6 cigarettes a day for 5 days. In addition, we used a separate group treated with NG-nitro-L-arginine methyl ester (an NO inhibitor) to confirm nitric oxide (NO) involvement in GSE effects.

Results: We showed for the first time that administration of GSE inhibited ALI and oxidative damage induced by CS. This is associated with decreased MMP-9 activity, decreased number of inflammatory cells in the bronchoalveolar lavage fluid, and reduced levels of lipid peroxidation. Our results indicate that beneficial effects of GSE are NO-dependent.

Conclusions: The study indicates that alteration of the oxidant-antioxidant balance is important in the pathogenesis of CS-induced ALI and suggests lung protective effects of GSE treatment in the mouse.

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Related in: MedlinePlus

Representative photomicrographs of mouse lung sections stained with hematoxylin and eosin (400×). (A) Control group: animals exposed to ambient air; (B) CS group: animals exposed to 6 commercial filtered cigarettes per day for 5 consecutive days; (C) CS+GSE group: animals exposed to 6 commercial filtered cigarettes per day for 5 consecutive days and treated with grape skin extract (200 mg/kg/day); (D) CS+GSE+L-NAME group: animals exposed to 6 commercial filtered cigarettes per day for 5 consecutive days and treated with grape skin extract (200 mg/kg/day) plus NG-nitro-L-arginine methyl ester (50 mg/kg/day).
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f2-medscimonit-17-8-br187: Representative photomicrographs of mouse lung sections stained with hematoxylin and eosin (400×). (A) Control group: animals exposed to ambient air; (B) CS group: animals exposed to 6 commercial filtered cigarettes per day for 5 consecutive days; (C) CS+GSE group: animals exposed to 6 commercial filtered cigarettes per day for 5 consecutive days and treated with grape skin extract (200 mg/kg/day); (D) CS+GSE+L-NAME group: animals exposed to 6 commercial filtered cigarettes per day for 5 consecutive days and treated with grape skin extract (200 mg/kg/day) plus NG-nitro-L-arginine methyl ester (50 mg/kg/day).

Mentions: Histological changes are illustrated in Figure 2. The lungs of control group mice showed parenchyma features consisting of alveoli connected to alveolar ducts, separated from each other only by thin alveolar septa (Figure 1A). The lungs of all CS mice showed small modifications including increased alveolar macrophages (AMs) and neutrophils (PMNs) in alveoli; however, no changes were observed in lung histoarchitecture (Figure 1B). The lungs of CS+GSE mice were similar to the control group, with few AMs and no or very rare PMNs (Figure 1C). Finally, the lungs of CS+GSE+L-NAME mice were similar to the CS group, with increased in AMs and PMNs. No changes were observed in elastic and collagen fibers of any group exposed to CS or ambient air.


Grape skin extract reduced pulmonary oxidative response in mice exposed to cigarette smoke.

Pires KM, Valença SS, Resende ÂC, Porto LC, Queiroz EF, Moreira DD, de Moura RS - Med. Sci. Monit. (2011)

Representative photomicrographs of mouse lung sections stained with hematoxylin and eosin (400×). (A) Control group: animals exposed to ambient air; (B) CS group: animals exposed to 6 commercial filtered cigarettes per day for 5 consecutive days; (C) CS+GSE group: animals exposed to 6 commercial filtered cigarettes per day for 5 consecutive days and treated with grape skin extract (200 mg/kg/day); (D) CS+GSE+L-NAME group: animals exposed to 6 commercial filtered cigarettes per day for 5 consecutive days and treated with grape skin extract (200 mg/kg/day) plus NG-nitro-L-arginine methyl ester (50 mg/kg/day).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3539621&req=5

f2-medscimonit-17-8-br187: Representative photomicrographs of mouse lung sections stained with hematoxylin and eosin (400×). (A) Control group: animals exposed to ambient air; (B) CS group: animals exposed to 6 commercial filtered cigarettes per day for 5 consecutive days; (C) CS+GSE group: animals exposed to 6 commercial filtered cigarettes per day for 5 consecutive days and treated with grape skin extract (200 mg/kg/day); (D) CS+GSE+L-NAME group: animals exposed to 6 commercial filtered cigarettes per day for 5 consecutive days and treated with grape skin extract (200 mg/kg/day) plus NG-nitro-L-arginine methyl ester (50 mg/kg/day).
Mentions: Histological changes are illustrated in Figure 2. The lungs of control group mice showed parenchyma features consisting of alveoli connected to alveolar ducts, separated from each other only by thin alveolar septa (Figure 1A). The lungs of all CS mice showed small modifications including increased alveolar macrophages (AMs) and neutrophils (PMNs) in alveoli; however, no changes were observed in lung histoarchitecture (Figure 1B). The lungs of CS+GSE mice were similar to the control group, with few AMs and no or very rare PMNs (Figure 1C). Finally, the lungs of CS+GSE+L-NAME mice were similar to the CS group, with increased in AMs and PMNs. No changes were observed in elastic and collagen fibers of any group exposed to CS or ambient air.

Bottom Line: In addition, we used a separate group treated with NG-nitro-L-arginine methyl ester (an NO inhibitor) to confirm nitric oxide (NO) involvement in GSE effects.This is associated with decreased MMP-9 activity, decreased number of inflammatory cells in the bronchoalveolar lavage fluid, and reduced levels of lipid peroxidation.Our results indicate that beneficial effects of GSE are NO-dependent.

View Article: PubMed Central - PubMed

Affiliation: Inflammation, Oxidative Stress and Cancer Laboratory - ICB/CCS/Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.

ABSTRACT

Background: Oxidative stress has been implicated in the pathogenesis and progression of chronic obstructive pulmonary disease (COPD), and cigarette smoke (CS) is known to be one of the major sources of oxidants in the lungs. We postulated that acute administration of GSE (grape skin extract) would either reduce or protect the ALI (acute lung inflammation) produced by CS via NO release.

Material/methods: We adopted a nutritional approach by investigating the inflammatory cells, metalloproteinase 9 (MMP-9) activity, and oxidative stress markers (superoxide dismutase - SOD; catalase - CAT; glutathione peroxidase (GPx) activities and malondialdehyde - MDA - levels) that play a role in the development of acute lung inflammation (ALI). Therefore, we tested an orally active antioxidant produced from grape skin manipulation (grape skin extract - GSE), in mice exposed to CS from 6 cigarettes a day for 5 days. In addition, we used a separate group treated with NG-nitro-L-arginine methyl ester (an NO inhibitor) to confirm nitric oxide (NO) involvement in GSE effects.

Results: We showed for the first time that administration of GSE inhibited ALI and oxidative damage induced by CS. This is associated with decreased MMP-9 activity, decreased number of inflammatory cells in the bronchoalveolar lavage fluid, and reduced levels of lipid peroxidation. Our results indicate that beneficial effects of GSE are NO-dependent.

Conclusions: The study indicates that alteration of the oxidant-antioxidant balance is important in the pathogenesis of CS-induced ALI and suggests lung protective effects of GSE treatment in the mouse.

Show MeSH
Related in: MedlinePlus