Skip to main content
SpringerLink
Log in

Green Tea Extract Inhibits Paraquat-Induced Pulmonary Fibrosis by Suppression of Oxidative Stress and Endothelin-l Expression

  • INTERSTITIAL LUNG DISEASE
  • Published:
Lung Aims and scope Submit manuscript

Abstract

Paraquat-induced pulmonary fibrosis involves two factors, direct injury by oxygen free radicals and indirect injury by inflammatory cells and fibroblasts. Endothelin-1 (ET-1) has been shown to act as a mediator of pulmonary fibrosis, and its formation increases during oxidative stress. We investigated whether green tea extract (GTE), which has antioxidant properties, inhibits paraquat-induced pulmonary fibrosis and whether ET-1 is involved in this process. Paraquat (0.3 mg/kg) was instilled into the right lungs of rats, following which the rats were either not further treated (Group P, n = 7), or they were administered 1% GTE mixed with feed (Group PG; n = 7) or the ETA receptor antagonist ZD2574 (10 mg/kg through gavage; Group PZ; n = 7) for two weeks. As control, we used rats instilled with saline (Group N; n = 6). Two weeks after paraquat instillation, we assayed the degree of pulmonary fibrosis by light microscopic morphometry and hydroxyproline content; lipid peroxidation as a marker of oxidative stresses by measurement of malondialdehyde (MDA); ET-1 by immunohistochemistry; and prepro-ET-1 mRNA expression by reverse transcription-polymerase chain reaction. Compared with Group N, significant pulmonary fibrosis was observed in Group P, accompanied by increases in MDA, ET-1, and prepro-ET-1 mRNA expression. Compared with Group P, Group PG showed significant decreases in pulmonary fibrosis, along with decreases in MDA, ET-1, and prepro-ET-1 mRNA expression. We also observed significant decreases in pulmonary fibrosis in Group PZ compared with Group P. These findings suggest that GTE inhibits paraquat-induced pulmonary fibrosis by suppression of oxidative stress and ET-1 expression.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Anjaneyulu M, Tirkey N, Chopra K (2003) Attenuation of cyclosporine-induced renal dysfunction by catechin: possible antioxidant mechanism. Ren Fail 25:691–707

    Article  PubMed  CAS  Google Scholar 

  2. Autor AP (1974) Reduction of paraquat toxicity by superoxide dismutase. Life Sci 14:1309–1319

    Article  PubMed  CAS  Google Scholar 

  3. Barnes PJ (1994) Endothelins and pulmonary diseases. J Appl Phsiol 77:1051–1059

    CAS  Google Scholar 

  4. Coker RK, Laurent GJ (1998) Pulmonary fibrosis: cytokines in the balance. Eur Respir J 11:1218–1221

    Article  PubMed  CAS  Google Scholar 

  5. Conte A, Pellegrini S, Tagliazucchi D (2003) Synergistic protection of PC 12 cells from beta-amyloid toxicity by resveratrol and catechin. Brain Res Bull 62:29–38

    Article  PubMed  CAS  Google Scholar 

  6. Cooper JA Jr, Zitnik RJ, Matthay RA (1988) Mechanisms of drug-induced pulmonary disease. Annu Rev Med 39:395–404

    Article  PubMed  Google Scholar 

  7. Copland GM, Kolin A, Shulman HS (1974) Fatal pulmonary intra-alveolar fibrosis after paraquat ingestion. N Engl J Med 291:290–292

    Article  PubMed  CAS  Google Scholar 

  8. Dubaybo BA, Durr RA, Thet LA (1987) Unilateral paraquat-induced lung fibrosis: evolution of changes in lung fibronectin and collagen after graded degrees of lung injury. J Toxicol Environ Health 22:439–457

    Article  PubMed  CAS  Google Scholar 

  9. Frei B, Higdon JV (2003) Antioxidant activity of tea polyphenols in vivo: evidence from animal studies. J Nutr 133:3275S–3284S

    PubMed  CAS  Google Scholar 

  10. Fujiki H, Suganuma M, Okabe S, et al. (2000) A new concept of tumor promotion by tumor necrosis factor-alpha, and cancer preventive agents (−)-epigallocatechin gallate and green tea–a review. Cancer Detect Prev 24:91–99

    PubMed  CAS  Google Scholar 

  11. Gauldie J, Jordana M, Cox G (1993) Cytokines and pulmonary fibrosis. Thorax 48:931–935

    PubMed  CAS  Google Scholar 

  12. Giaid A, Michel RP, Stewart DJ, et al. (1993) Expression of endothelin-1 in lungs of patients with cryptogenic fibrosing alveolitis. Lancet 341:1550–1554

    Article  PubMed  CAS  Google Scholar 

  13. Greenberg DB, Lyons SA, Last JA (1978) Paraquat-induced changes in the rate of collagen synthesis by rat lung explants. J Lab Clin Med 92:1033–1042

    PubMed  CAS  Google Scholar 

  14. Greenberg DB, Reiser KM, Last JA (1978) Correlation of biochemical and morphologic manifestations of acute pulmonary fibrosis in rats administered paraquat. Chest 74:421–425

    PubMed  CAS  Google Scholar 

  15. Henry JP, Stephens-Larson P (1984) Reduction of chronic psychosocial hypertension in mice by decaffeinated tea. Hypertension 6:437–444

    PubMed  CAS  Google Scholar 

  16. Higuchi A, Yonemitsu K, Koreeda A, Tsunenari S (2003) Inhibitory activity of epigallocatechin gallate (EGCg) in paraquat-induced microsomal lipid peroxidationr—a mechanism of protective effects of EGCg against paraquat toxicity. Toxicology 183:143–149

    Article  PubMed  CAS  Google Scholar 

  17. Hocher B, Schwarz A, Fagan KA, et al. (2000) Pulmonary fibrosis and chronic lung inflammation in ET-1 transgenic mice. Am J Respir Cell Mol Biol 23:19–26

    PubMed  CAS  Google Scholar 

  18. Hsu SM, Raine L, Fanger H (1981) Use of avidin–biotin–peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem 29:577–580

    PubMed  CAS  Google Scholar 

  19. Isemura M, Saeki K, Kimura T, et al. (2000) Tea catechins and related polyphenols as anti-cancer agents. Biofactors 13:81–85

    PubMed  CAS  Google Scholar 

  20. Kaehler J, Sill B, Koester R, et al. (2002) Endothelin-1 mRNA and protein in vascular wall cells is increased by reactive oxygen species. Clin Sci 103 Suppl 48:176S–178S

    PubMed  CAS  Google Scholar 

  21. Kahaleh MB (1991) Endothelin, an endothelial-dependent vasoconstrictor in scleroderma: enhanced production and profibrotic action. Arthritis Rheum 34:978–983

    PubMed  CAS  Google Scholar 

  22. Kahler J, Mendel S, Weckmuller J, et al. (2000) Oxidative stress increases synthesis of big endothelin-1 by activation of the endothelin-1 promoter. J Mol Cell Cardiol 32:1429–1437

    Article  PubMed  CAS  Google Scholar 

  23. Lee JH, Chun YG, Lee IC, et al. (2001) Pathogenic role of endothelin-1 in hemodynamic dysfunction in experimental acute pulmonary thromboembolism. Am J Respir Crit Care Med 164:1282–1287

    PubMed  CAS  Google Scholar 

  24. Mallat A, Fouassier L, Preaux AM, et al. (1995) Growth inhibitory properties of endothelin-1 in human hepatic myofibroblastic Ito cells: an endothelin B receptor-mediated pathway. J Clin Invest 96:42–49

    Article  PubMed  CAS  Google Scholar 

  25. Minkes RK, Bellan JA, Saroyan RM, et al. (1990) Analysis of cardiovascular and pulmonary responses to endothelin-1 and endothelin-3 in the anesthetized cat. J Pharmacol Exp Ther 253:1118–1125

    PubMed  CAS  Google Scholar 

  26. Nakano J, Takizawa H, Ohtoshi T, et al. (1994) Endotoxin and proinflammatory cytokines stimulate endothelin-1 expression and release by airway epithelial cells. Clin Exp Allergy 24:330–336

    Article  PubMed  CAS  Google Scholar 

  27. Okabe S, Ochiai Y, Aida M, et al. (1999) Mechanistic aspects of green tea as a cancer preventive: effect of components on human stomach cancer cell lines. Jpn J Cancer Res 90:733–739

    PubMed  CAS  Google Scholar 

  28. Park SH, Saleh D, Giaid A, Michel RP (1997) Increased endothelin-1 in bleomycin-induced pulmonary fibrosis and the effect of an endothelin receptor antagonist. Am J Respir Crit Care Med 156:600–608

    PubMed  CAS  Google Scholar 

  29. Peacock AJ, Dawes KE, Shock A, et al. (1992) Endothelin-1 and endothelin-3 induce chemotaxis and replication of pulmonary artery fibroblasts. Am J Respir Cell Mol Biol 7:492–429

    PubMed  CAS  Google Scholar 

  30. Sachinidis A, Seul C, Seewald S, et al. (2000) Green tea compounds inhibit tyrosine phosphorylation of PDGF beta-receptor and transformation of A172 human glioblastoma. FEBS Lett 471:51–55

    Article  PubMed  CAS  Google Scholar 

  31. Schoenberger CI, Rennard SI, Bitterman PB, et al. (1984) Paraquat-induced pulmonary fibrosis. Role of the alveolitis in modulating the development of fibrosis. Am Rev Respir Dis 129:168–173

    PubMed  CAS  Google Scholar 

  32. Skillrud DM, Martin WJ 2nd (1984) Paraquat-induced injury of type II alveolar cells. An in vitro model of oxidant injury. Am Rev Respir Dis 129:995–999

    PubMed  CAS  Google Scholar 

  33. Smith LL (1987) Mechanism of paraquat toxicity in lung and its relevance to treatment. Hum Toxicol 6:31–36

    Article  PubMed  CAS  Google Scholar 

  34. Smith P, Heath D, Kay JM (1974) The pathogenesis and structure of paraquat-induced pulmonary fibrosis in rats. J Pathol 114:57–67

    Article  PubMed  CAS  Google Scholar 

  35. Sueoka N, Suganuma M, Sueoka E, et al. (2001) A new function of green tea: prevention of lifestyle-related disease. Ann N Y Acad Sci 928:274–280

    Article  PubMed  CAS  Google Scholar 

  36. Williams SN, Shih H, Guenette DK, et al. (2000) Comparative studies on the effects of green tea extracts and individual tea catechins on human CYP1A gene expression. Chem Biol Interact 128:211–229

    Article  PubMed  CAS  Google Scholar 

  37. Xu FP, Chen MS, Wang YZ, et al. (2004) Leptin induces hypertrophy via endothelin-1-reactive oxygen species pathway in cultured neonatal rat cardiomyocytes. Circulation 110:1269–1275

    Article  PubMed  CAS  Google Scholar 

  38. Zhao BL, Li XJ, He RG, Cheng SJ, Xin WJ (1989) Scavenging effect of extracts of green tea and natural antioxidants on active oxygen radicals. Cell Biophys 14:175–785

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This article was supported by grants 2000-119 and 2003-119 from Asan Life Science Institute. Supported by a grant of the Korean Health 21 R:D Project, Ministry of Health: welfare, Republic of Korea (0412-CR03-0704-0001).

Author information

Authors and Affiliations

  1. Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Asan Medical Center, College of Medicine, University of Ulsan, 388-1 Poongnab-dong, 138-736, Songpa-gu, Seoul, Republic of Korea

    Yeon-Mok Oh

  2. Department of Internal Medicine, College of Medicine, Wonkwang University, Iksan, Republic of Korea

    Hak-Ryul Kim

  3. Department of Internal Medicine, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Republic of Korea

    Byung-Kyu Park, Yeon-Mok Oh, Hyun-Kuk Kim, Tae-Sun Shim & Sang-Do Lee

  4. Department of Molecular and Cellular Biology, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea

    Yun-Song Lee

  5. National Research Laboratory, Department of Laboratory Medicine, College of Medicine, Seoul National University, Seoul, Republic of Korea

    Dong-Soon Lee

  6. Asan Life Science Institute, Seoul, Republic of Korea

    Joo-Young Kim

Authors
  1. Hak-Ryul Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Byung-Kyu Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yeon-Mok Oh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yun-Song Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Dong-Soon Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hyun-Kuk Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Joo-Young Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Tae-Sun Shim
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Sang-Do Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yeon-Mok Oh.

Additional information

Hak-Ryul Kim and Byung-Kyu Park contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kim, HR., Park, BK., Oh, YM. et al. Green Tea Extract Inhibits Paraquat-Induced Pulmonary Fibrosis by Suppression of Oxidative Stress and Endothelin-l Expression. Lung 184, 287–295 (2006). https://doi.org/10.1007/s00408-005-2592-x

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00408-005-2592-x

Keywords

Search

Navigation