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Piroxicam-copper complexes: Inhibition of polymorphonuclear leukocyte migration toPseudomonas aeruginosa chemotactinsin vivo and superoxide dismutase-like activityin vitro

  • Inflammation
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Abstract

Piroxicam-copper (Cu2+ complexes, formed spontaneously by mixing solutions of piroxicam and CuSO4 (1∶1 Cu2+:piroxicam), inhibited the superoxide anion-catalyzed reduction of ferricytochrome C in a doserelated fashion. Addition of ethylenediaminetetraacetate to the mixture decreased in a dose-related manner the superoxide dismutase (SOD)-like activity of piroxicam-Cu2+. Piroxicam alone (10−5 M, final concentration) did not display SOD-like activity but 10−5 M Cu2+ exhibited significant activity, similar to that of piroxicam-Cu2+. Intraperitoneal treatment of mice with either 0.64 mg/kg piroxicam or its Cu2+ complexes (0.64 mg/kg piroxicam +0.12 mg/kg Cu2+) was equally effective in diminishing both the migration of polymorphonuclear leukocytes (PMNL) to the airways and the content of myeloperoxidase activity in the lungs, induced by aerosol challenge withPseudomonas aeruginosa peptide chemotactins. Therefore, piroxicam-Cu2+ complexes may provide both the anti-inflammatory activity of piroxicam plus the SOD-like activity of Cu2+.

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References

  1. P. M. Henson and R. B. Johnston Jr.,Perspectives: Tissue injury in inflammation. Oxidants, proteinases and cationic proteins. J. Clin. Invest.79, 669–674 (1987).

    Google Scholar 

  2. G. C. Kindt, J. E. Gadek and J. E. Weiland,Initial recruitment of neutrophils to alveolar structures in acute lung injury. J. Appl. Physiol.70, 1575–1585 (1991).

    Google Scholar 

  3. P. A. Ward, J. S. Warren and K. J. Johnson,Oxygen radicals, inflammation and tissue injury. Free Rad. Biol. Med.5, 403–408 (1988).

    Google Scholar 

  4. D. O. Sordelli, M. C. Cerquetti, G. El-Tawil, P. W. Ramwell, A. M. Hooke and J. A. Bellanti,Ibuprofen modifies the inflammatory response of the murine lungs to Pseudomonas aeruginosa. Eur. J. Respir. Dis.67, 118–127 (1985).

    Google Scholar 

  5. D. O. Sordelli, M. C. Cerquetti, P. A. Fontán and R. P. Meiss,Piroxicam treatment protects mice from lethal pulmonary challenge with Pseudomonas aeruginosa. J. Infect. Dis.159, 232–238 (1989).

    Google Scholar 

  6. D. O. Sordelli, M. C. Cerquetti, P. A. Fontán and V. E. García, Pseudomonas aeruginosapneumonia: Treatment with non-steroidal anti-inflammatory agents to prevent lung tissue damage. InAntibiotics and Chemotherapy (Eds. N. Hoiby, S. S. Pedersen, G. H. Shand, G. Döring and I. A. Holder) pp. 247–253, Karger, Basilea, Switzerland 1989.

    Google Scholar 

  7. M. C. McGahan,Copper and aspirin treatment increase the antioxidant activity of plasma. Agents and Actions31, 59–64 (1990).

    Google Scholar 

  8. M. Roch-Arveiller, V. Revelant, D. Pham Huy, L. Maman, J. R. J. Sorenson and J. P. Giroud,Effects of some nonsteroidal anti-inflammatory drug copper complexes on polymorphonuclear leukocyte oxidative metabolism. Agents and Actions31, 65–71 (1990).

    Google Scholar 

  9. E. Lengfelder and U. Weser,Superoxide dismutation by low molecular weight Cu-complexes, Bull. Europ. Physiopathol. Resp.17 (Suppl.), 73–80 (1981).

    Google Scholar 

  10. P. A. Fontán, C. R. Amura, V. E. García, M. C. Cerquetti and D. O. Sordelli,Preliminary characterization of Pseudomonas aeruginosa peptide chemotactins for polymorphonuclear leukocytes. Infect. Immun.60, 2465–2469 (1992).

    Google Scholar 

  11. J. R. J. Sorenson,Copper complexes as active forms of antiarthritic agents. Med. Chem.19, 135–148 (1976).

    Google Scholar 

  12. J. A. Metcalf, J. I. Gallin, W. M. Nauseef and R. K. Root,Function related to microbicidal activity. InLaboratory Manual of Neutrophil Function, pp. 116–117, Raven Press, New York 1986.

    Google Scholar 

  13. D. O. Sordelli, M. C. Cerquetti, A. M. Hooke and J. A. Bellanti,The effect of chemotactins released by Staphylococcus aureus andPseudomonas aeruginosa on the murine respiratory tract. Infect. Immun.49, 265–269 (1985).

    Google Scholar 

  14. D. O. Sordelli, B. J. Zeligs, M. C. Cerquetti, A. M. Hooke and J. A. Bellanti,Inflammatory responses to Pseudomonas aeruginosa and Staphylococcus aureus in the murine lung. Eur. J. Respir. Dis.66, 31–39 (1985).

    Google Scholar 

  15. D. O. Sordelli, M. Djafari, V. E. García, P. A. Fontán and G. Döring,Age-dependent pulmonary clearance of Pseudomonas aeruginosa in a mouse model: Diminished migration of polymorphonuclear leukocytes to N-formyl-methionyl-leucyl-phenylalanine. Infect. Immun.60 1724–1727 (1992).

    Google Scholar 

  16. J. A. Badwey and M. L. Karnowsky,N ADH oxidase from guinea pig polymorphonuclear leukocytes. Methods Enzymol.132, 365–368 (1986).

    Google Scholar 

  17. D. O. Sordelli, P. A. Fontán, R. P. Meiss, R. A. Ruggiero, R. P. Meiss and O. D. Bustuoabad,Anti-inflammation induced by counter-irritation or by treatment with nonsteroidal agents inhibits the growth of a tumour of nondetected immunogenicity. Br. J. Cancer60, 734–738 (1989).

    Google Scholar 

  18. E. Paur and E. Lengfelder,Can copper piroxicam complexes catalyze the elimination of superoxide radicals? Fresenius Z. Anal. Chem.317, 693–694 (1984).

    Google Scholar 

  19. U. Weser, E. Lengfelder, K. H. Sellinger and L. Schobotz,Reactivity of chelated copper with superoxide. InInflammatory Diseases and Copper (Ed. J. R. J. Sorenson) pp. 513–524, Humana Press, Clifton, New Jersey, 1982.

    Google Scholar 

  20. S. Spisani, C. Marangoni, and S. Traniello,Effect of antiinflammatory drugs on leukocyte superoxide production by soluble and particulate stimuli. Biochem. Internat.9, 1–8 (1984).

    Google Scholar 

  21. D. Frechilla, B. Las Heras, M. Ucelay, E. Parrondo, G. Craciunescu and E. Cenarruzabeitía,On the mechanism of the anti-inflammatory activity of some copper (II) complexes. Arzneim. Forschung40, 1008–1010 (1990).

    Google Scholar 

  22. Y. K. Youn, C. Lalonde and R. Demling,Oxidants and the pathophysiology of burn and smoke inhalation injury. Free Rad. Biol. Med.12, 409–415 (1992).

    Google Scholar 

  23. J. R. J. Sorenson,Copper complexes: A physiological approach to treatment of chronic diseases. Comp. Ther.11, 49–64 (1985).

    Google Scholar 

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Authors and Affiliations

  1. Dept. Microbiology, FCM-UBA, Paraguay 2155 P-12, 1121, Buenos Aires, Argentina

    D. O. Sordelli, P. A. Fontán & C. R. Amura

  2. Department of Pediatrics, Georgetown University School of Medicine, 20007, Washington, DC

    D. O. Sordelli

Authors
  1. D. O. Sordelli
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  2. P. A. Fontán
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  3. C. R. Amura
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Sordelli, D.O., Fontán, P.A. & Amura, C.R. Piroxicam-copper complexes: Inhibition of polymorphonuclear leukocyte migration toPseudomonas aeruginosa chemotactinsin vivo and superoxide dismutase-like activityin vitro . Agents and Actions 38, 196–201 (1993). https://doi.org/10.1007/BF01976211

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  • DOI: https://doi.org/10.1007/BF01976211

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