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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

Bronchoalveolar lavage (BAL) fluid cellularity at the end of the experiment. Macrophages (A, C) and neutrophils (B, D) were collected from BAL fluid. Panels on the left show data from cigarette smoke-exposed animals plus treatment; Panels on the right show data from ambient air-exposed animals plus treatment. Control group: animals exposed to ambient air; CS group: animals exposed to 6 commercial filtered cigarettes per day for 5 consecutive days; 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); 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); GSE group: animals exposed to ambient air and treated with grape skin extract (200 mg/kg/day); L-NAME group: animals exposed to ambient air and treated with grape skin extract (200 mg/kg/day) plus NG-nitro-L-arginine methyl ester (50 mg/kg/day); Data are mean values (n 4–6) with their standard errors represented by vertical bars. One-way ANOVA was performed followed by the Tukey post-test was used for statistical analysis. (a) Mean value was significantly different from that of the Control group. (b) Mean value was significantly different from that of the CS group. (c) Mean value was significantly different from that CS+GSE group. (*) Mean value was significantly different from that of the Control group; (#) Mean value was significantly different from that of the GSE group.
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f3-medscimonit-17-8-br187: Bronchoalveolar lavage (BAL) fluid cellularity at the end of the experiment. Macrophages (A, C) and neutrophils (B, D) were collected from BAL fluid. Panels on the left show data from cigarette smoke-exposed animals plus treatment; Panels on the right show data from ambient air-exposed animals plus treatment. Control group: animals exposed to ambient air; CS group: animals exposed to 6 commercial filtered cigarettes per day for 5 consecutive days; 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); 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); GSE group: animals exposed to ambient air and treated with grape skin extract (200 mg/kg/day); L-NAME group: animals exposed to ambient air and treated with grape skin extract (200 mg/kg/day) plus NG-nitro-L-arginine methyl ester (50 mg/kg/day); Data are mean values (n 4–6) with their standard errors represented by vertical bars. One-way ANOVA was performed followed by the Tukey post-test was used for statistical analysis. (a) Mean value was significantly different from that of the Control group. (b) Mean value was significantly different from that of the CS group. (c) Mean value was significantly different from that CS+GSE group. (*) Mean value was significantly different from that of the Control group; (#) Mean value was significantly different from that of the GSE group.

Mentions: The AMs and PMNs numbers in BAL fluid are shown in Figure 3. The 160% increase in AMs number in the CS group when compared to the control group (p<0.001) was 55% reduced by GSE treatment (p<0.001). However, when L-NAME was given together with GSE, AMs numbers were similar to CS group. In addition, the pattern of PMNs influx was similar to the AMs (Figure 3A). There was a 25% increase in AMs number in C57BL/6 mice that were exposed to ambient air for 5 consecutive days and treated with L-NAME (p<0.05; Figure 3C). PMNs increased 950% in CS (p<0.001) and 770% CS+GSE+L-NAME (p<0.001) when compared to the control group. PMN numbers of the CS+GSE group showed no differences when compared with PMN numbers of the control group (Figure 3B). There was a 95% increase in PNMs number in C57BL/6 mice that were exposed to ambient air for 5 consecutive days and treated with L-NAME (p<0.001; Figure 3D).


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)

Bronchoalveolar lavage (BAL) fluid cellularity at the end of the experiment. Macrophages (A, C) and neutrophils (B, D) were collected from BAL fluid. Panels on the left show data from cigarette smoke-exposed animals plus treatment; Panels on the right show data from ambient air-exposed animals plus treatment. Control group: animals exposed to ambient air; CS group: animals exposed to 6 commercial filtered cigarettes per day for 5 consecutive days; 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); 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); GSE group: animals exposed to ambient air and treated with grape skin extract (200 mg/kg/day); L-NAME group: animals exposed to ambient air and treated with grape skin extract (200 mg/kg/day) plus NG-nitro-L-arginine methyl ester (50 mg/kg/day); Data are mean values (n 4–6) with their standard errors represented by vertical bars. One-way ANOVA was performed followed by the Tukey post-test was used for statistical analysis. (a) Mean value was significantly different from that of the Control group. (b) Mean value was significantly different from that of the CS group. (c) Mean value was significantly different from that CS+GSE group. (*) Mean value was significantly different from that of the Control group; (#) Mean value was significantly different from that of the GSE group.
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getmorefigures.php?uid=PMC3539621&req=5

f3-medscimonit-17-8-br187: Bronchoalveolar lavage (BAL) fluid cellularity at the end of the experiment. Macrophages (A, C) and neutrophils (B, D) were collected from BAL fluid. Panels on the left show data from cigarette smoke-exposed animals plus treatment; Panels on the right show data from ambient air-exposed animals plus treatment. Control group: animals exposed to ambient air; CS group: animals exposed to 6 commercial filtered cigarettes per day for 5 consecutive days; 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); 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); GSE group: animals exposed to ambient air and treated with grape skin extract (200 mg/kg/day); L-NAME group: animals exposed to ambient air and treated with grape skin extract (200 mg/kg/day) plus NG-nitro-L-arginine methyl ester (50 mg/kg/day); Data are mean values (n 4–6) with their standard errors represented by vertical bars. One-way ANOVA was performed followed by the Tukey post-test was used for statistical analysis. (a) Mean value was significantly different from that of the Control group. (b) Mean value was significantly different from that of the CS group. (c) Mean value was significantly different from that CS+GSE group. (*) Mean value was significantly different from that of the Control group; (#) Mean value was significantly different from that of the GSE group.
Mentions: The AMs and PMNs numbers in BAL fluid are shown in Figure 3. The 160% increase in AMs number in the CS group when compared to the control group (p<0.001) was 55% reduced by GSE treatment (p<0.001). However, when L-NAME was given together with GSE, AMs numbers were similar to CS group. In addition, the pattern of PMNs influx was similar to the AMs (Figure 3A). There was a 25% increase in AMs number in C57BL/6 mice that were exposed to ambient air for 5 consecutive days and treated with L-NAME (p<0.05; Figure 3C). PMNs increased 950% in CS (p<0.001) and 770% CS+GSE+L-NAME (p<0.001) when compared to the control group. PMN numbers of the CS+GSE group showed no differences when compared with PMN numbers of the control group (Figure 3B). There was a 95% increase in PNMs number in C57BL/6 mice that were exposed to ambient air for 5 consecutive days and treated with L-NAME (p<0.001; Figure 3D).

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