DOI QR코드

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The effects of pycnogenol on antioxidant enzymes in a mouse model of ozone exposure

  • Lee, Min-Sung (Department of Internal Medicine, Soonchunhyang University Bucheon Hospital) ;
  • Moon, Kuk-Young (Department of Internal Medicine, Soonchunhyang University Bucheon Hospital) ;
  • Bae, Da-Jeong (Department of Internal Medicine, Soonchunhyang University Bucheon Hospital) ;
  • Park, Moo-Kyun (Department of Otolaryngology, Soonchunhyang University Bucheon Hospital) ;
  • Jang, An-Soo (Department of Internal Medicine, Soonchunhyang University Bucheon Hospital)
  • 발행 : 2013.03.01

초록

Background/Aims: Ozone is an environmentally reactive oxidant, and pycnogenol is a mixture of f lavonoid compounds extracted from pine tree bark that have antioxidant activity. We investigated the effects of pycnogenol on reactive nitrogen species, antioxidant responses, and airway responsiveness in BALB/c mice exposed to ozone. Methods: Antioxidant levels were determined using high performance liquid chromatography with electrochemical detection. Nitric oxide (NO) metabolites in bronchoalveolar lavage (BAL) fluid from BALB/c mice in filtered air and 2 ppm ozone with pycnogenol pretreatment before ozone exposure (n = 6) were quantified colorimetrically using the Griess reaction. Results: Uric acid and ascorbic acid concentrations were significantly higher in BAL fluid following pretreatment with pycnogenol, whereas ${\gamma}$-tocopherol concentrations were higher in the ozone exposed group but were similar in the ozone and pycnogenol pretreatment groups. Retinol and ${\gamma}$-tocopherol concentrations tended to increase in the ozone exposure group but were similar in the ozone and pycnogenol pretreatment groups following ozone exposure. Malonylaldehyde concentrations increased in the ozone exposure group but were similar in the ozone and pycnogenol plus ozone groups. The nitrite and total NO metabolite concentrations in BAL fluid, which parallel the in vivo generation of NO in the airways, were significantly greater in the ozone exposed group than the group exposed to filtered air, but decreased with pycnogenol pretreatment. Conclusions: Pycnogenol may increase levels of antioxidant enzymes and decrease levels of nitrogen species, suggesting that antioxidants minimize the effects of acute ozone exposure via a protective mechanism.

키워드

참고문헌

  1. Jang AS, Yeum CH, Son MH. Epidemiologic evidence of a relationship between airway hyperresponsiveness and exposure to polluted air. Allergy 2003;58:585-588. https://doi.org/10.1034/j.1398-9995.2003.00205.x
  2. Jang AS, Choi IS, Yang SY, et al. Antioxidant responsiveness in BALB/c mice exposed to ozone. Respiration 2005;72:79-84. https://doi.org/10.1159/000083405
  3. Jang AS, Choi IS, Lee JU, Park SW, Lee JH, Park CS. Changes in the expression of NO synthase isoforms after ozone: the effects of allergen exposure. Respir Res 2004;5:5. https://doi.org/10.1186/1465-9921-5-5
  4. Jang AS, Choi IS, Kim SW, Song BC, Yeum CH, Jung JY. Airway obstruction after acute ozone exposure in BALB/c mice using barometric plethysmography. Korean J Intern Med 2003;18:1-5. https://doi.org/10.3904/kjim.2003.18.1.1
  5. Jang AS, Choi IS, Lee JU. Neuronal nitric oxide synthase is associated with airway obstruction in BALB/c mice exposed to ozone. Respiration 2003;70:95-99. https://doi.org/10.1159/000068406
  6. Jang AS, Choi IS, Koh YI, Park CS, Lee JS. The relationship between alveolar epithelial proliferation and airway obstruction after ozone exposure. Allergy 2002;57:737-740. https://doi.org/10.1034/j.1398-9995.2002.23569.x
  7. Jang AS, Choi IS, Lee JH, Park CS. Prolonged ozone exposure in an allergic airway disease model: adaptation of airway responsiveness and airway remodeling. Respir Res 2006;7:24. https://doi.org/10.1186/1465-9921-7-24
  8. Leikauf GD, Zhao Q, Zhou S, Santrock J. Ozonolysis products of membrane fatty acids activate eicosanoid metabolism in human airway epithelial cells. Am J Respir Cell Mol Biol 1993;9:594-602. https://doi.org/10.1165/ajrcmb/9.6.594
  9. Mikerov AN, Umstead TM, Gan X, et al. Impact of ozone exposure on the phagocytic activity of human surfactant protein A (SP-A) and SP-A variants. Am J Physiol Lung Cell Mol Physiol 2008;294:L121-L130. https://doi.org/10.1152/ajplung.00288.2007
  10. Kafoury RM, Pryor WA, Squadrito GL, Salgo MG, Zou X, Friedman M. Induction of inflammatory mediators in human airway epithelial cells by lipid ozonation products. Am J Respir Crit Care Med 1999;160:1934-1942. https://doi.org/10.1164/ajrccm.160.6.9902025
  11. Kafoury RM, Pryor WA, Squadrito GL, Salgo MG, Zou X, Friedman M. Lipid ozonation products activate phospholipases A2, C, and D. Toxicol Appl Pharmacol 1998;150:338-349. https://doi.org/10.1006/taap.1998.8418
  12. Packer L, Rimbach G, Virgili F. Antioxidant activity and biologic properties of a procyanidin-rich extract from pine (Pinus maritima) bark, pycnogenol. Free Radic Biol Med 1999;27:704-724. https://doi.org/10.1016/S0891-5849(99)00090-8
  13. Rice-Evans CA, Miller NJ. Antioxidant activities of flavonoids as bioactive components of food. Biochem Soc Trans 1996;24:790-795. https://doi.org/10.1042/bst0240790
  14. Boege F, Straub T, Kehr A, et al. Selected novel flavones inhibit the DNA binding or the DNA religation step of eukaryotic topoisomerase I. J Biol Chem 1996;271:2262-2270. https://doi.org/10.1074/jbc.271.4.2262
  15. Koley AP, Buters JT, Robinson RC, Markowitz A, Friedman FK. Differential mechanisms of cytochrome P450 inhibition and activation by alpha-naphthof lavone. J Biol Chem 1997;272:3149-3152. https://doi.org/10.1074/jbc.272.6.3149
  16. De Azevedo WF Jr, Mueller-Dieckmann HJ, Schulze-Gahmen U, Worland PJ, Sausville E, Kim SH. Structural basis for specificity and potency of a flavonoid inhibitor of human CDK2, a cell cycle kinase. Proc Natl Acad Sci U S A 1996;93:2735-2740. https://doi.org/10.1073/pnas.93.7.2735
  17. Moini H, Guo Q, Packer L. Enzyme inhibition and protein-binding action of the procyanidin-rich french maritime pine bark extract, pycnogenol: effect on xanthine oxidase. J Agric Food Chem 2000;48:5630-5639. https://doi.org/10.1021/jf000618s
  18. Saliou C, Rimbach G, Moini H, et al. Solar ultravioletinduced erythema in human skin and nuclear factorkappa-B-dependent gene expression in keratinocytes are modulated by a French maritime pine bark extract. Free Radic Biol Med 2001;30:154-160. https://doi.org/10.1016/S0891-5849(00)00445-7
  19. Ueda T, Armstrong D. Preventive effect of natural and synthetic antioxidants on lipid peroxidation in the mammalian eye. Ophthalmic Res 1996;28:184-192. https://doi.org/10.1159/000267901
  20. van Jaarsveld H, Kuyl JM, Schulenburg DH, Wiid NM. Effect of flavonoids on the outcome of myocardial mitochondrial ischemia/reperfusion injury. Res Commun Mol Pathol Pharmacol 1996;91:65-75.
  21. Rong Y, Li L, Shah V, Lau BH. Pycnogenol protects vascular endothelial cells from t-butyl hydroperoxide induced oxidant injury. Biotechnol Ther 1994;5:117-126.
  22. Cheshier JE, Ardestani-Kaboudanian S, Liang B, et al. Immunomodulation by pycnogenol in retrovirus-infected or ethanol-fed mice. Life Sci 1996;58:PL87-PL96.
  23. Committee of the Environmental and Occupational Health Assembly of the American Thoracic Society. Health effects of outdoor air pollution. Am J Respir Crit Care Med 1996;153:3-50. https://doi.org/10.1164/ajrccm.153.1.8542133
  24. Holtzman MJ, Fabbri LM, O'Byrne PM, et al. Importance of airway inflammation for hyperresponsiveness induced by ozone. Am Rev Respir Dis 1983;127:686-690.
  25. Gordon T, Taylor BF, Amdur MO. Ozone inhibition of tissue cholinesterase in guinea pigs. Arch Environ Health 1981;36:284-288. https://doi.org/10.1080/00039896.1981.10667639
  26. Kelly FJ, Blomberg A, Frew A, Holgate ST, Sandstrom T. Antioxidant kinetics in lung lavage fluid following exposure of humans to nitrogen dioxide. Am J Respir Crit Care Med 1996;154(6 Pt 1):1700-1705. https://doi.org/10.1164/ajrccm.154.6.8970358
  27. Wiester MJ, Winsett DW, Richards JH, Jackson MC, Crissman KM, Costa DL. Ozone adaptation in mice and its association with ascorbic acid in the lung. Inhal Toxicol 2000;12:577-590. https://doi.org/10.1080/08958370050030958
  28. Freed AN, Cueto R, Pryor WA. Antioxidant transport modulates peripheral airway reactivity and inflammation during ozone exposure. J Appl Physiol 1999;87:1595-1603. https://doi.org/10.1152/jappl.1999.87.5.1595
  29. Jacky JP. A plethysmograph for long-term measurements of ventilation in unrestrained animals. J Appl Physiol 1978;45:644-647. https://doi.org/10.1152/jappl.1978.45.4.644
  30. Mudway IS, Housley D, Eccles R, et al. Differential depletion of human respiratory tract antioxidants in response to ozone challenge. Free Radic Res 1996;25:499-513. https://doi.org/10.3109/10715769609149072
  31. Bieri JG, Poukka RK, Prival EL. Determination of alpha-tocopherol in erythrocytes by gas-liquid chromatography. J Lipid Res 1970;11:118-123.
  32. Blomberg A, Mudway IS, Nordenhall C, et al. Ozoneinduced lung function decrements do not correlate with early airway inf lammatory or antioxidant responses. Eur Respir J 1999;13:1418-1428. https://doi.org/10.1183/09031936.99.13614299
  33. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979;95:351-358. https://doi.org/10.1016/0003-2697(79)90738-3
  34. Greenberg SS, Xie J, Spitzer JJ, et al. Nitro containing L-arginine analogs interfere with assays for nitrate and nitrite. Life Sci 1995;57:1949-1961. https://doi.org/10.1016/0024-3205(95)02181-H
  35. Bast A, Weseler AR, Haenen GR, den Hartog GJ. Oxidative stress and antioxidants in interstitial lung disease. Curr Opin Pulm Med 2010;16:516-520.
  36. Finkel T. Signal transduction by reactive oxygen species. J Cell Biol 2011;194:7-15. https://doi.org/10.1083/jcb.201102095
  37. Balaban RS, Nemoto S, Finkel T. Mitochondria, oxidants, and aging. Cell 2005;120:483-495. https://doi.org/10.1016/j.cell.2005.02.001
  38. Comhair SA, Erzurum SC. Redox control of asthma: molecular mechanisms and therapeutic opportunities. Antioxid Redox Signal 2010;12:93-124. https://doi.org/10.1089/ars.2008.2425
  39. Kliment CR, Oury TD. Oxidative stress, extracellular matrix targets, and idiopathic pulmonary fibrosis. Free Radic Biol Med 2010;49:707-717. https://doi.org/10.1016/j.freeradbiomed.2010.04.036
  40. Wood LG, Wark PA, Garg ML. Antioxidant and antiinf lammatory effects of resveratrol in airway disease. Antioxid Redox Signal 2010;13:1535-1548. https://doi.org/10.1089/ars.2009.3064
  41. Park HS, Kim SR, Lee YC. Impact of oxidative stress on lung diseases. Respirology 2009;14:27-38. https://doi.org/10.1111/j.1440-1843.2008.01447.x
  42. Cho YS, Moon HB. The role of oxidative stress in the pathogenesis of asthma. Allergy Asthma Immunol Res 2010;2:183-187. https://doi.org/10.4168/aair.2010.2.3.183
  43. Nadeem A, Masood A, Siddiqui N. Oxidant: antioxidant imbalance in asthma: scientific evidence, epidemiological data and possible therapeutic options. Ther Adv Respir Dis 2008;2:215-235. https://doi.org/10.1177/1753465808094971
  44. Macnee W, Rahman I. Oxidants and antioxidants as therapeutic targets in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1999;160(5 Pt 2):S58-S65. https://doi.org/10.1164/ajrccm.160.supplement_1.15
  45. Rohdewald P. Pycnogenol. In: Rice-Evans C, Packer L, eds. Flavonoids in Health and Disease. New York: Marcel Dekker, 1998:405-419.
  46. Masquelier J, inventor. Plant extract with a proanthocyanidins content as therapeutic agent having radical scavenging effect and use thereof. United States patent US 4,698,360. 1987 Oct 6.
  47. Blazso G, Gabor M, Sibbel R, Rohewald P. Antiinflammatory and superoxide radical scavenging activities of procyanidins containing extract from the bark of Pinus pinaster Sol. and its fractions. Pharmaceut Pharmacol Lett 1994;3:217-220.
  48. Virgili F, Kobuchi H, Packer L. Procyanidins extracted from Pinus maritima (Pycnogenol): scavengers of free radical species and modulators of nitrogen monoxide metabolism in activated murine RAW 264.7 macrophages. Free Radic Biol Med 1998;24:1120-1129. https://doi.org/10.1016/S0891-5849(97)00430-9
  49. Heffner JE, Repine JE. Pulmonary strategies of antioxidant defense. Am Rev Respir Dis 1989;140:531-554. https://doi.org/10.1164/ajrccm/140.2.531
  50. Burton GW, Joyce A, Ingold KU. First proof that vitamin E is major lipid-soluble, chain-breaking antioxidant in human blood plasma. Lancet 1982;2:327.
  51. McCay PB. Vitamin E: interactions with free radicals and ascorbate. Annu Rev Nutr 1985;5:323-340. https://doi.org/10.1146/annurev.nu.05.070185.001543
  52. Romieu I, Meneses F, Ramirez M, et al. Antioxidant supplementation and respiratory functions among workers exposed to high levels of ozone. Am J Respir Crit Care Med 1998;158:226-232. https://doi.org/10.1164/ajrccm.158.1.9712053
  53. Kari F, Hatch G, Slade R, Crissman K, Simeonova PP, Luster M. Dietary restriction mitigates ozone-induced lung inflammation in rats: a role for endogenous antioxidants. Am J Respir Cell Mol Biol 1997;17:740-747. https://doi.org/10.1165/ajrcmb.17.6.2844
  54. Morabia A, Menkes MJ, Comstock GW, Tockman MS. Serum retinol and airway obstruction. Am J Epidemiol 1990;132:77-82. https://doi.org/10.1093/oxfordjournals.aje.a115645
  55. Shahar E, Folsom AR, Melnick SL, et al. Does dietary vitamin A protect against airway obstruction? The Atherosclerosis Risk in Communities (ARIC) Study Investigators. Am J Respir Crit Care Med 1994;150:978-982. https://doi.org/10.1164/ajrccm.150.4.7921473

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