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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

Measurements of catalase (CAT) activity in lung homogenates from all experimental groups. 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). 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.
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f5-medscimonit-17-8-br187: Measurements of catalase (CAT) activity in lung homogenates from all experimental groups. 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). 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.

Mentions: We analyzed 3 specific enzymes involved in the antioxidant endogenous defense mechanisms. SOD activity is shown in Figure 4. CS exposure increased SOD activity 66% in lung homogenates when compared to the control group (p<0.001). GSE administration restored SOD activity compared to the control group. The CS+L-NAME+GSE group showed SOD activity similar to the CS group. Catalase activity increased 45% in lung homogenates after CS exposure (p<0.05) (Figure 5). CAT values in the CS+GSE group were similar to the CS group. Glutathione Peroxidase activity is shown in Figure 6. GSE treatment reduced the 250% increase in GPx activity observed in the CS group (p<0.001), but it was still high when compared with the control group (105%, p<0.001). In contrast, concomitant GSE and L-NAME administrations in animals exposed to CS resulted in a 67% increase of GPx activity when compared to the CS+GSE group (p<0.001).


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)

Measurements of catalase (CAT) activity in lung homogenates from all experimental groups. 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). 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.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3539621&req=5

f5-medscimonit-17-8-br187: Measurements of catalase (CAT) activity in lung homogenates from all experimental groups. 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). 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.
Mentions: We analyzed 3 specific enzymes involved in the antioxidant endogenous defense mechanisms. SOD activity is shown in Figure 4. CS exposure increased SOD activity 66% in lung homogenates when compared to the control group (p<0.001). GSE administration restored SOD activity compared to the control group. The CS+L-NAME+GSE group showed SOD activity similar to the CS group. Catalase activity increased 45% in lung homogenates after CS exposure (p<0.05) (Figure 5). CAT values in the CS+GSE group were similar to the CS group. Glutathione Peroxidase activity is shown in Figure 6. GSE treatment reduced the 250% increase in GPx activity observed in the CS group (p<0.001), but it was still high when compared with the control group (105%, p<0.001). In contrast, concomitant GSE and L-NAME administrations in animals exposed to CS resulted in a 67% increase of GPx activity when compared to the CS+GSE group (p<0.001).

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