• Sulagna Dutta university of Calcuuta
  • Biswadev Bishayi University of Calcutta


Aminoguanidine, Ciprofloxacin, Meclofenamic acid, S aureus, Septic arthritis


Objective: Staphylococcus aureus (S. aureus) is a potent causative organism of septic arthritis. In this study, ciprofloxacin was used to nullify the bacterial burden in mice infected with pathogenic strain of S. aureus. Since, endogenous nitric oxide (NO) and prostaglandins (PG) are involved in several inflammatory diseases, in vivo modulation of their levels via Aminoguanidine (AMG) and Meclofenamic acid (MFA), in combination with ciprofloxacin, are used to modulate the inflammatory conditions in bacterial arthritis.

Methods: Septic arthritis were induced in mice by S. aureus (i. v.) infection followed by AMG or MFA treatment with ciprofloxacin. Mice were sacrificed at 3, 9 and 15 days post-infection (DPI). The clinical signs of septic arthritis were recorded, bacterial density determination in blood, spleen and synovial tissue, several biochemical, enzyme assays and histological studies of the synovial joint was performed.

Results: AMG or MFA treatment alone does not lead to bacterial clearance since endogenous NO or PG was limited for bacterial killing. Ciprofloxacin treatment in combination with either AMG or MFA showed mitigation of bacterial burden as is evident from the CFU count and maximum reduction in inflammatory conditions, apparent from the reduced percentage of induction of septic arthritis, decreased myeloperoxidase (MPO), lysozyme activities, level of serum uric acid and creatinine as well as from the histological examinations.

Conclusion: The combination treatment of ciprofloxacin along with immune modulators, AMG or MFA may lead to diminution of the inflammatory build up caused by S. aureus induced septic arthritis in mice.



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Author Biographies

Sulagna Dutta, university of Calcuuta

Department of Physiology, University of Calcutta

Biswadev Bishayi, University of Calcutta

Department of physiology, Professor


Bukowski M, Wladyka B, Dubin G. Exfoliative toxins of Staphylococcus aureus. Toxins 2010;2:1148-65.

Rigby KM, DeLeo FR. Neutrophils in innate host defense against Staphylococcus aureus infections. Semin Immunopathol 2012;34:237-59.

Variations in amount of TSST-1 produced by clinical methicillin resistant Staphylococcus aureus(MRSA) isolates and allelic variation in accessory gene regulator (agr) locus. BMC Microbiol 2009;9:52-6.

Sharma-Kuinkel BK, Zhang Y, Yan Q, Ahn SH, Fowler VG. Host gene expression profiling and in vivo cytokine studies to characterize the role of linezolid and vancomycin in methicillin-resistant Staphylococcus aureus (MRSA) murine sepsis model. PLoS One 2013;8:1-10.

Edwards AM, Potts JR, Josefsson E, Massey RC. Staphylococcus aureus host cell invasion and virulence in sepsis is facilitated by the multiple repeats within FnBPA. PLoS Pathogen 2010;6:1-16.

Clement S, Vaudaux P, Francois P, Schrenzel J, Huggler E, Kampf S, et al. Evidence of an intracellular reservoir in the nasal mucosa of patients with recurrent Staphylococcus aureus rhinosinusitis. J Infect Dis 2005;192:1023-8.

Dzwonkowska J, Kurlenda J, Baczkowski B, Mazurkiewicz S, Uzunov I, Ziółkowski W, et al. The effect of antibiotic therapy on the incidence of Staphylococcus aureus infections in orthopaedic patients. Ortop Traumatol Rehabil 2007;9:532-47.

Tan CM, Alex G, Therien AG, Lu J, Lee SH, Caron A, et al. Restoring Methicillin-Resistant Staphylococcus aureus Susceptibility to β-Lactam antibiotics. Sci Transl Med 2012;4:126-35.

Moran GJ, Krishnadasan A, Gorwitz RJ, Fosheim GE, McDougal LK, Carey RB, et al. Methicillin-resistant S. aureus infections among patients in the emergency department. N Engl J Med 2006;355:666-74.

Brunner M, Hollenstein U, Delacher S, Jäger D, Schmid R, Lackner E, et al. Distribution and antimicrobial activity of ciprofloxacin in human soft tissues. Antimicrob Agents Chemother 1999;43:1307-9.

Chatterji M, Unniraman S, Mahadevan S, Nagaraja V. Effect of different classes of inhibitors on DNA gyrase from Mycobacterium smegmatis. J Antimicrob Chemother 2001;48:479-85.

Kobayashi Y. The regulatory role of nitric oxide in proinflammatory cytokine expression during the induction and resolution of inflammation. J Leuko Biol 2010;88:1157-62.

Mal P, Dutta S, Bandyopadhyay D, Dutta K, Basu A, Bishayi B. Gentamicin in combination with ascorbic acid Regulates the severity of Staphylococcus aureus Infection induced septic arthritis in mice. Scand J Immunol 2012;76:528-40.

Burchill MA, Nardelli DT, Douglas M. Inhibition of interleukin-17 prevents the development of arthritis in vaccinated mice challenged with Borrelia burgdorferi. Infect Immun 2003;71:3437-42.

Sen R, Das D, Bishayi B. Staphylococcal catalase regulates its virulence and induces arthritis in catalase deficient mice. Indian J Physiol Pharmacol 2009;53:307-17.

Oser BL. Hawk’s physiological chemistry. McGraw Hill Book Company; 1976. p. 1044-8.

Lefkowitz DL, Gelderman MP, Fuhrmann SR, Graham S, Starnes JD, Lefkowitz SS, et al. Neutrophil myeloperoxidase-macrophage interactions perpetuate chronic inflammation associated with experimental arthritis. Clin Immunol 1999;91:145-55.

Shugar D. The measurement of lysozyme activity and the ultra-violet inactivation of lysozyme. Biochim Biophys Acta 1952;8:302-9.

Lubberts E, Joosten Leo AB, Oppers B, Bersselaar L, Christina JJ. IL-1-Independent Role of IL-17 in synovial inflammation and joint destruction during collagen-induced arthritis. J Immunol 2001;167:1004-13.

Fisher RA, Yates R. Statistical tables for biological, Agricultural and medical Research. Longman Group, London; 1974.

Farhad AR, Razavi M, Alavi Nejad P. The use of aminoguanidine, a selective inducible nitric oxide synthase inhibitor, to evaluate the role of nitric oxide on periapical healing. DRJ 2011;8:187-202.

Mitchell MD, Flint AP. Use of meclofenamic acid to investigate the role of prostaglandin biosynthesis during induced parturition in sheep. J Endocrinol 1978;76:101-9.

Pérez-Novo CA, Waeytens A, Claeys C, Cauwenberge PV, Bachert C. Staphylococcus aureus enterotoxin b regulates prostaglandin E2 synthesis, Growth, and migration in nasal tissue fibroblasts. J Infect Dis 2008;197:1036-43.

Ghaemi-Oskouie F, Shi Y. The role of uric acid as an endogenous danger signal in immunity and inflammation. Curr Rheumatol Rep 2011;13:160-6.

Davies MJ. Myeloperoxidase-derived oxidation: mechanisms of biological damage and its prevention. J Clin Biochem Nutr 2011;48:8-19.

Ricciotti E, FitzGerald GA. Prostaglandins and Inflammation. Arterioscler Thromb Vasc Biol 2011;31:986-1000.

Urb M, Sheppard DC. The role of mast cells in the defence against pathogens. PLoS Pathog 2012;8:e1002619.

Mortensen MB, Kjolby M, Gunnersen S, Larsen JV, Palmfeldt J, Falk J, et al. Targeting sortilin in immune cells reduces proinflammatory cytokines and atherosclerosis. J Clin Invest 2014;124(12):5317–22.

Sutti S, Jindal A, Locatelli I, Vacchiano M, Gigliotti L, Bozzola C, Albano E. Adaptive immune responses triggered by oxidative stress contribute to hepatic inflammation in NASH. Hepatology 2014;59:886-97.



How to Cite

Dutta, S., and B. Bishayi. “EFFECTS OF CIPROFLOXACIN IN COMBINATION WITH EITHER AMINOGUANIDINE OR MECLOFENAMIC ACID IN MODULATING S. AUREUS INDUCED SEPTIC ARTHRITIS IN MICE”. International Journal of Pharmacy and Pharmaceutical Sciences, vol. 7, no. 6, June 2015, pp. 355-61, https://journals.innovareacademics.in/index.php/ijpps/article/view/5795.



Original Article(s)