Taurine 11 pp 1033-1048 | Cite as

Combined Biological Effects of N-Bromotaurine Analogs and Ibuprofen. Part II: Influence on a Local Defense System

  • Angelika Peruń
  • Marta Ciszek-Lenda
  • Maria Walczewska
  • Aneta Kiecka
  • Anna Białecka
  • Markus Nagl
  • Waldemar Gottardi
  • Janusz MarcinkiewiczEmail author
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1155)


The stable N-bromotaurine analogs (N-dibromo-dimethyl taurine, N-monobromo-dimethyl taurine), and bromamine T (BAT) show anti-inflammatory and microbicidal properties. These bromamines are good candidates for a treatment of skin infectious/inflammatory diseases as local antiseptics. Ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), is commonly used in various infectious/inflammatory diseases due to its analgesic and antipyretic therapeutic effects. However, systemic administration of ibuprofen may also result in adverse side effects. It has been reported that ibuprofen enhances serum levels of TNF-α and worsens secondary skin infections caused by invasive streptococci (S. pyogenes). Recently we have demonstrated that bromamines inhibit the stimulatory effect of ibuprofen on the production of inflammatory cytokines (TNF-α, IL-6). The aim of this study was to examine the combined antibacterial actions of ibuprofen and bromamines against S. pyogenes and their joint effect on the generation of reactive oxygen species (ROS) by activated neutrophils and macrophages. We have shown that the microbicidal activity of bromamines against S. pyogenes was not altered by ibuprofen. On the other hand, co-administration of ibuprofen and bromamines markedly decreased the generation of ROS by activated neutrophils and macrophages. Finally, we discuss how the antioxidant combined effect of bromamines and ibuprofen may affect a local defense system.


Taurine N-bromotaurine analogs Antiseptics Ibuprofen ROS Phagocytes Infectious skin diseases S. pyogenes 





hypobromous acid


N-bromotaurine, taurine bromamine

DM-NBr2T (Br-422)



bromamine T, N-bromo-N-sodio-p-toluenesulfonamide


luminol-dependent chemiluminescence


opsonized zymosan


reactive oxygen species


nitric oxide


polymorphonuclear cells, murine peritoneal neutrophils

murine peritoneal macrophages

S. pyogenes

Streptococcus pyogenes


minimal bactericidal concentration



This study was supported by grants from the Jagiellonian University Medical College (grant no. K/ZDS/005454).


  1. Benbarek H, Ayad A, Deby-Dupont G, Boukraa L, Serteyn D (2012) Modulatory effects of non-steroidal anti-inflammatory drugs on the luminol and lucigenin amplified chemiluminescence of equine neutrophils. Vet Res Commun 3:29–33CrossRefGoogle Scholar
  2. Bryant AE, Bayer CR, Aldape MJ, Stevens DL (2015) The roles of injury and nonsteroidal anti-inflammatory drugs in the development and outcomes of severe group A streptococcal soft tissue infections. Curr Opin Infect Dis 28:231–239CrossRefGoogle Scholar
  3. Çağıltay E, Kaplan M, Nalbant S, Akpak YK, Sahan B, Akmaz İ (2015) Does non-steroidal anti-inflammatory drugs increase tumor necrosis factor-alpha levels? Int J Res Med Sci 3:2280–2283CrossRefGoogle Scholar
  4. Carey PD, Jenkins JK, Byrne K, Walsh CJ, Fowler AA, Sugerman HJ (1992) The neutrophil respiratory burst and tissue injury in septic acute lung injury: the effect of cyclooxygenase inhibition in swine. Surgery 1:45–55Google Scholar
  5. Castro L, Alvarez MN, Radi R (1996) Modulatory role of nitric oxide on superoxide-dependent luminol chemiluminescence. Arch Biochem Biophys 333:179–188CrossRefGoogle Scholar
  6. Costa D, Moutinho L, Lima JL, Fernandes E (2006) Antioxidant activity and inhibition of human neutrophil oxidative burst mediated by arylpropionic acid non-steroidal anti-inflammatory drugs. Biol Pharm Bull 29(8):1659–1670CrossRefGoogle Scholar
  7. Díaz-Rodríguez L, García-Martínez O, De Luna-Bertos E, Ramos-Torrecillas J, Ruiz C (2012) Effect of ibuprofen on proliferation, differentiation, antigenic expression, and phagocytic capacity of osteoblasts. J Bone Miner Metab 30:554–560CrossRefGoogle Scholar
  8. Ding AH, Nathan CF, Stuehr DJ (1988) Release of reactive nitrogen intermediates from mouse peritoneal macrophages: comparison of activating cytokines and evidence for independent production. J Immunol 141:2407–2412PubMedPubMedCentralGoogle Scholar
  9. Gottardi W, Nagl M (2010) N-chlorotaurine, a natural antiseptic with outstanding tolerability. J Antimicrob Chemother 65:399–409CrossRefGoogle Scholar
  10. Gottardi W, Klotz S, Nagl M (2014) Superior bactericidal activity of N-bromine compounds compared to their N-chlorine analogues can be reversed under protein load. J Appl Microbiol 116:1427–1437CrossRefGoogle Scholar
  11. Hasegawa H, Suzuki K, Nakaji S, Sugawara K (1997) Analysis and assessment of the capacity of neutrophils to produce reactive oxygen species in a 96-well microplate format using lucigenin- and luminol-dependent chemiluminescence. J Immunol Methods 210:1–10CrossRefGoogle Scholar
  12. Hay AD, Costelloe C, Redmond N, Montgomery A, Fletcher M, Hollinghurst S, Peters TJ (2008) Paracetamol plus ibuprofen for the treatment of fever in children (PITCH): randomised controlled trial. BMJ 337:1302CrossRefGoogle Scholar
  13. Kalinski P (2012) Regulation of immune response by prostaglandin E2. J Immunol 188:21–28CrossRefGoogle Scholar
  14. Klebanoff SJ (2005) Myeloperoxidase: friend and foe. J Leukoc Biol 77:598–625CrossRefGoogle Scholar
  15. Le Turnier P, Boutoille D, Joyau C, Veyrac G, Asseray N (2017) Bacterial infections and NSAIDs exposure? Seek septic complications. Eur J Intern Med 41:33–34CrossRefGoogle Scholar
  16. Maderazo EG, Breaux SP, Woronick CL (1984) Inhibition of human polymorphonuclear leukocyte cell responses by ibuprofen. J Pharm Sci 73:1403–1406CrossRefGoogle Scholar
  17. Marcinkiewicz J (2009) Taurine bromamine: a new therapeutic option in inflammatory skin diseases. Pol Arch Med Wewn 119:673–676PubMedPubMedCentralGoogle Scholar
  18. Marcinkiewicz J (2010) Taurine bromamine (TauBr)-its role in immunity and new perspectives for clinical use. J Biomed Sci 17:S3CrossRefGoogle Scholar
  19. Marcinkiewicz J, Mak M, Bobek M, Biedroń R, Białecka A, Koprowski M, Kontny E, Maśliński W (2005) Is there a role of taurine bromamine in in-flammation? Interactive effects with nitrite and hydrogen peroxide. Inflamm Res 54:42–49CrossRefGoogle Scholar
  20. Marcinkiewicz J, Wojas-Pelc A, Walczewska M, Lipko-Godlewska S, Jachowicz R, Maciejewska A, Białecka A, Kasprowicz A (2008) Topical taurine bromamine, a new candidate in the treatment of moderate inflammatory acne vulgaris: a pilot study. Eur J Dermatol 18:433–439PubMedPubMedCentralGoogle Scholar
  21. Müller G, Kramer A (2008) Biocompatibility index of antiseptic agents by parallel assessment of antimicrobial activity and cellular cytotoxicity. J Antimicrob Chemother 61:1281–1287CrossRefGoogle Scholar
  22. Nagl M, Nguyen VA, Gottardi W, Ulmer H, Höpfl R (2003) Tolerability and efficacy of N chlorotaurine in comparison with chloramine T for treatment of chronic leg ulcers with a purulent coating: a randomized phase II study. Br J Dermatol 149:590–597CrossRefGoogle Scholar
  23. Nair CG, Lalithakumari R, Senan PI (1978) Bromamine-T as a new oxidimetric titrant. Talanta 25:525–527CrossRefGoogle Scholar
  24. Nielsen VG, Webster RO (1987) Inhibition of human polymorphonuclear leukocyte functions by ibuprofen. Immunopharmacology 13:61–71CrossRefGoogle Scholar
  25. Parij N, Nagy AM, Fondu P, Nève J (1998) Effects of non-steroidal anti-inflammatory drugs on the luminol and lucigenin amplified chemiluminescence of human neutrophils. Eur J Pharmacol 352:299–305CrossRefGoogle Scholar
  26. Park E, Schuller-Levis G, Jia JH, Quinn MR (1997) Preactivation exposure of RAW 264.7 cells to taurine chloramines attenuates subsequent production of nitric oxide and expression of iNOS mRNA. J Leukoc Biol 61:161–166CrossRefGoogle Scholar
  27. Rainsford KD (2009) Ibuprofen: pharmacology, efficacy and safety. Inf Dent 17:275–342Google Scholar
  28. Stevens DL (1995) Could nonsteroidal anti-inflammatory drugs (NSAIDs) enhance the progression of bacterial infections to toxic shock syndrome? Clin Infect Dis 21:977–980CrossRefGoogle Scholar
  29. Thomas EL, Bozeman PM, Jefferson MM, King CC (1995) Oxidation of bromide by the human leukocyte enzymes myeloperoxidase and eosinophil peroxidase. Formation of bromamines. J BiolChem 270:2906–2913Google Scholar
  30. Titheradge MA (1991) Nitric oxide in septic shock. Biochim Biophys Acta 1411:437–455CrossRefGoogle Scholar
  31. Walczewska M, Peruń A, Białecka A, Śróttek M, Jamróz W, Dorożyński P, Jachowicz R, Kulinowski P, Nagl M, Gottardi W, Marcinkiewicz J (2017) Comparative analysis of microbicidal and anti-inflammatory properties of novel taurine bromamine derivatives and bromamine T. Adv Exp Med Biol 975:515–534CrossRefGoogle Scholar
  32. Walczewska M, Ciszek-Lenda M, Peruń A, Kiecka A, Nazimek K, Kyriakopoulos A, Nagl M, Gottardi W, Marcinkiewicz M (submitted) Combined biological effects of N-bromotaurine analogs and ibuprofen. Part I: influence on inflammatory properties of macrophages. Adv Exp Med BiolGoogle Scholar
  33. Wang JF, Komarov P, Sies H, de Groot H (1991) Contribution of nitric oxide synthase to luminol-dependent chemiluminescence generated by phorbol-ester-activated Kupffer cells. Biochem J 279:311–314CrossRefGoogle Scholar
  34. Wang JF, Komarov P, de Groot H (1993) Luminol chemiluminescence in rat macrophages and granulocytes: the role of NO, O2-/H2O2, and HOCl. Arch Biochem Biophys 304:189–196CrossRefGoogle Scholar
  35. Weiss SJ, Klein R, Slivka A, Wei M (1982) Chlorination of taurine by human neutrophils: evidence for hypochlorous acid generation. J Clin Invest 70:598–603CrossRefGoogle Scholar
  36. Weng TC, Chen CC, Toh HS, Tang HJ (2011) Ibuprofen worsens Streptococcus pyogenes soft tissue infections in mice. J Microbiol Immunol Infect 44:418–423CrossRefGoogle Scholar
  37. Wilkinson BL, Cramer PE, Varvel NH, Reed-Geaghan E, Jiang Q, Szabo A, Herrup K, Lamb BT, Landreth GE (2012) Ibuprofen attenuates oxidative damage through NOX2 inhibition in Alzheimer’s disease. Neurobiol Aging 33:21–32CrossRefGoogle Scholar
  38. Zerr DM, Alexander ER, Duchin JS, Koutsky LA, Rubens CE (1999) A case-control study of necrotizing fasciitis during primary varicella. Pediatrics 103:783–790CrossRefGoogle Scholar
  39. Zgliczyński JM, Stelmaczyńska T (1975) Chlorinating ability of human phagocytosing leucocytes. Eur J Biochem 56:157–162CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Angelika Peruń
    • 1
  • Marta Ciszek-Lenda
    • 1
  • Maria Walczewska
    • 1
  • Aneta Kiecka
    • 1
  • Anna Białecka
    • 2
  • Markus Nagl
    • 3
  • Waldemar Gottardi
    • 3
  • Janusz Marcinkiewicz
    • 1
    Email author
  1. 1.Chair of ImmunologyJagiellonian University Medical CollegeKrakowPoland
  2. 2.Center of Microbiological Research and Autovaccines Ltd.KrakowPoland
  3. 3.Division of Hygiene and Medical MicrobiologyMedical University of InnsbruckInnsbruckAustria

Personalised recommendations