Skip to main content
SpringerLink
Log in

Modulation of cyclophosphamide-induced early lung injury by curcumin, an anti-inflammatory antioxidant

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Cyclophosphamide causes lung injury in rats through its ability to generate free radicals with subsequent endothelial and epithelial cell damage. In order to observe the protective effects of a potent anti-inflammatory antioxidant, curcumin (diferuloyl methane) on cyclophosphamide-induced early lung injury, healthy pathogen free male Wistar rats were exposed to 20 mg/100 g body weight of cyclophosphamide, intraperitoneally as a single injection. Prior to cyclophosphamide intoxication oral administration of curcumin was performed daily for 7 days. At various time intervals (2, 3, 5 and 7 days post insult) serum and lung samples were analyzed for angiotensin converting enzyme, lipid peroxidation, reduced glutathione and ascorbic acid. Bronchoalveolar lavage fluid was analyzed for biochemical constituents. The lavage cells were examined for lipid peroxidation and glutathione content. Excised lungs were analyzed for antioxidant enzyme levels. Biochemical analyses revealed time course increases in lavage fluid total protein, albumin, angiotensin converting enzyme (ACE), lactate dehydrogenase, N-acetyl-β-D-glucosaminidase, alkaline phosphatase, acid phosphatase, lipid peroxide levels and decreased levels of glutathione (GSH) and ascorbic acid 2, 3, 5 and 7 days after cyclophosphamide intoxication. Increased levels of lipid peroxidation and decreased levels of glutathione and ascorbic acid were seen in serum, lung tissue and lavage cells of cyclophosphamide groups. Serum angiotensin converting enzyme activity increased which coincided with the decrease in lung tissue levels. Activities of antioxidant enzymes were reduced with time in the lungs of cyclophosphamide groups. However, a significant reduction in lavage fluid biochemical constituents, lipid peroxidation products in serum, lung and lavage cells with concomitant increase in antioxidant defense mechanisms occurred in curcumin fed cyclophosphamide rats. Therefore, our results suggest that curcumin is effective in moderating the cyclophosphamide induced early lung injury and the oxidant-antioxidant imbalance was partly abolished by restoring the glutathione (GSH) with decreased levels of lipid peroxidation.

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

Similar content being viewed by others

References

  1. Batist G, Andrews JL Jr: Pulmonary toxicity of antineoplastic drugs. J Am Med Assoc 246: 1449–1453, 1981

    Google Scholar 

  2. Collis CH, Wilson CM, Jones JM: Cyclophosphamide induced lung damage in mice: Protection by a small preliminary dose. Br J Cancer 41: 901–907, 1980

    Google Scholar 

  3. Gould VE, Miller J: Sclerosing alveolitis induced by cyclophosphamide. Am J Pathol 81: 513–530, 1975

    Google Scholar 

  4. Cooper JAD Jr, White DA, Matthay RA: Drug induced pulmonary disease. Am Rev Respir Dis 133: 321–340, 1986

    Google Scholar 

  5. Kanekal S, Fraiser L, Kehrer JP: Pharmacokinetics, metabolic activation and lung toxicity of cyclophosphamide in C57/B16 and ICR mice. Toxicol Appl Pharmacol 114: 1–8, 1992

    Google Scholar 

  6. Patel JM: Metabolism and pulmonary toxicity of cyclophosphamide. Pharmac Ther 47: 137–146, 1990

    Google Scholar 

  7. Srivastava R, Srimal RC: Modification of certain inflammation-induced biochemical changes by curcumin. Indian J Med Res 81: 215–223, 1985

    Google Scholar 

  8. Nishigaki I, Kuttan R, Oku H, Ashoori F, Abe H, Yagi K: Suppressive effect of curcumin on lipid peroxidation induced in rats by carbon tetrachloride or60co-irradiation. J Clin Biochem Nutr 13: 23–29, 1992

    Google Scholar 

  9. Sharma OP: Antioxidant activity of curcumin and related compounds. Biochem Pharmacol 25: 1811–1812, 1976

    Google Scholar 

  10. Pulla Reddy, A Ch, Lokesh BR: Studies on spice principles as antioxidants in the inhibition of lipid peroxidation of rat liver microsomes. Mol Cell Biochem 111: 117–124, 1992

    Google Scholar 

  11. Venkatesan N, Chandrakasan G: Cyclophosphamide induced early biochemical changes in lung lavage fluid and alterations in lavage cell function. Lung 172: 147–158, 1994

    Google Scholar 

  12. Soudamini KK, Kuttan R: Chemoprotective effect of curcumin against cyclophosphamide toxicity. Indian J Pharm Sci 54: 213–217, 1992

    Google Scholar 

  13. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ: Protein measurement with the Folin phenol reagent. J Biol Chem 193: 265–275, 1951

    Google Scholar 

  14. Varley H: Practical Clinical Biochemistry. CBS Publishers and Distributors, Delhi, 1988, pp 243–244

    Google Scholar 

  15. Cushman DW, Cheung HS: Spectrophotometric assay and properties of the angiotensin converting enzyme of rabbit lung. Biochem Pharmacol 20: 1637–1647, 1971

    Google Scholar 

  16. King J: Practical Clinical Enzymology. Von Nostrand D. Company, London, 1965, pp 106–107

    Google Scholar 

  17. Moore JC, Morris JW: A simple automated colorimetric method for determination of N-acetyl-β-D-glucosaminidase. Ann Clin Biochem 19: 157–159, 1982

    Google Scholar 

  18. King J: Practical Clinical Enzymology. Von Nostrand D. Company, London, 1965, pp 264–265

    Google Scholar 

  19. Cynamon HA, Isenberg JN, Nguyenco H: Erythrocyte malondialdehyde releasein vitro: a functional measure of vitamin E status. Clin Chim Acta 151: 169–176, 1985

    Google Scholar 

  20. Hogberg J, Larson RE, Kristoferson A, Orrenius S: NADPH-dependent reductase solubilized from microsomes by peroxidation and its activity. Biochem Biophys Res Commun 56: 836–842, 1974

    Google Scholar 

  21. Moron LS, Depierre JW, Mannerwik B: Levels of glutathione, glutathione reductase and glutathione S-transferase activities in rat lung and liver. Biochim Biophys Acta 582: 67–78, 1979

    Google Scholar 

  22. Omaye ST Turnbull JD, Sauberlich HE: Selected methods for the determination of ascorbic acid in animal cells, tissues and fluids. In: D.B. McCormick and L.D. Wright (eds). Methods in Enzymology. Academic Press, New York, 1979, pp 7–8

    Google Scholar 

  23. Ells HA, Kirkman HN: A colorimetric method, for assay of erythrocytic glucose-6-phosphate dehydrogenase. Proc Soc Exptl Biol Med 106: 607–609, 1961

    Google Scholar 

  24. Misra HP, Fridovich I: The role of superoxide anion in the autooxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem 247: 3170–3175, 1972

    Google Scholar 

  25. Takahara S, Hamilton BH, Nell JV, Kobara TY, Ogura Y, Nishimura ET: Hypocatalasemia: a new genetic carrier state. J Clin Invest 29: 610–619, 1960

    Google Scholar 

  26. Necheles TF, Boles TA, Allen DM: Erythrocyte glutathione peroxidase deficiency and hemolytic disease of the newborn infant. J Pediatr 72: 319–324, 1968

    Google Scholar 

  27. Habig WH, Pabst MJ, Jakoby WB: Glutathione S-transferases. The first enzymatic step in mercapturic acid formation. J Biol Chem 249: 7130–7139, 1974

    Google Scholar 

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

    Google Scholar 

  29. Rebello G, Mason JK: Pulmonary histological appearances in fatal paraquat poisoning. Histopathology 2: 53–66, 1978

    Google Scholar 

  30. Vijeyaratnam GS, Corrin B: Experimental paraquat poisoning. A histopathological and electron-optical study of the changes in the lung. J Pathol 103: 123–129 1971

    Google Scholar 

  31. Giri SN, Schwartz LW, Hollinger MA, Freywald ME, Schiedt MJ Zuckerman JE: Biochemical and structural alterations of hamster lungs in response to intratracheal administration of bleomycin. Exp Mol Pathol 33: 1–14, 1980

    Google Scholar 

  32. Hampson ECGM, Eyles DW, Pond SM: Effect of paraquat on canine bronchoalveolar lavage fluid. Toxicol Appl Pharmacol 98: 206–215, 1989

    Google Scholar 

  33. Driscoll KE, Maurer JK, Poynter J, Higgins, J, Asquith T, Miller NSC: Stimulation of rat alveolar macrophage fibronectin release in a cadmium chloride model of lung injury and fibrosis. Toxicol Appl Pharmacol 116: 30–37, 1992

    Google Scholar 

  34. Schultze AE, Wagner JG, White SM, Roth RA: Early indications of monocrotaline pyrrole-induced lung injury in rats. Toxicol Appl Pharmacol 109: 41–50, 1991

    Google Scholar 

  35. Lew DB, Chodimella V, Murlas CG: Guinea pig ozone-induced airway hyperreactivity is associated with increased N-acetyl-β-D-glucosaminidase activity in bronchoalveolar lavage fluid. Lung 168: 273–283, 1990

    Google Scholar 

  36. Cochrane CG: Immunologic tissue injury mediated by neutrophilic leukocytes. Adv Immunol 9 97–167, 1968

    Google Scholar 

  37. Fox RB, Hoidal JR, Brown DM, Repine JE: Pulmonary inflammation due to oxygen toxicity: Involvement of chemotactic factors and polymorphonuclear leukocytes. Am Rev Respir Dis 123: 521–523, 1981

    Google Scholar 

  38. Weiss SJ: Tissue destruction of neutrophils. N Engl J Med 320: 365–376, 1989

    Google Scholar 

  39. Cooper JAD Jr, Merrill WW, Reynolds HY Cyclophosphamide modulation of bronchoalveolar cellular populations and macrophage oxidative metabolism: Possible mechanisms of pulmonary pharmacotoxicity. Am Rev Respir Dis 134: 108–114, 1986

    Google Scholar 

  40. Srimal RC, Dhawan BN: Pharmacology of diferuloyl methane (curcumin), a non-steroidal anti-inflammatory agent. J Pharm Pharmacol 25: 447–452, 1973

    Google Scholar 

  41. Deodhar SD, Sethi R, Srimal RC: Preliminary study on antirheumatic activity of curcumin (diferuloyl methane). Indian J Med Res 71: 632–634, 1980

    Google Scholar 

  42. Patel JM, Block ER, Hood CI: Biochemical indices of cyclophosphamide-induced lung injury. Toxicol Appl Pharmacol 76: 128–138, 1984

    Google Scholar 

  43. Patel JM: Stimulation of cyclophosphamide-induced pulmonary microsomal lipid peroxidation by oxygen. Toxicology 45: 79–91, 1987

    Google Scholar 

  44. Patel JM, Block ER: Cyclophosphamide induced depression of the antioxidant defense mechanisms of the lung. Exptl Lung Res 8: 153–165, 1985

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biochemistry, Central Leather Research Institute, Adyar, 600 020, Madras, India

    Narayanan Venkatesan & Gowri Chandrakasan (Head)

Authors
  1. Narayanan Venkatesan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gowri Chandrakasan
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Venkatesan, N., Chandrakasan, G. Modulation of cyclophosphamide-induced early lung injury by curcumin, an anti-inflammatory antioxidant. Mol Cell Biochem 142, 79–87 (1995). https://doi.org/10.1007/BF00928916

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00928916

Key words

Search

Navigation