Abstract
The aim of this study was to measure the levels of purines in serum of rats experimentally infected with Leptospira interrogans serovar Icterohaemorrhagiae. For this purpose, 24 adult male Wistar rats were divided into two groups: A, not infected (subgroups A1 and A2), and B, infected (subgroups B1 and B2), which were intraperitoneally inoculated (day 0) with 2 × 108 leptospires/animal. Blood samples were collected on days 15 (A1 and B1) and 30 PI (A2 and B2) for analysis of purine levels in serum (adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), adenosine, inosine, hypoxanthine, xanthine, and uric acid). The levels of ATP, AMP, adenosine, and xanthine increased (P < 0.015), while a reduction (P < 0.015) in the concentration of ADP and inosine occurred at day 15 PI. On day 30 PI, ATP, ADP, adenosine, and uric acid significantly increased (P < 0.015), while xanthine level was reduced (P < 0.015). The correlation among the infection and purine levels lead us to suggest the purinergic system as a compensatory mechanism during the leptospirosis infection, mainly due to the actions of ATP, which usually is involved in a pro-inflammatory response, followed by a protective action of ADP and adenosine on the clotting events, along with a protective cellular damage caused by the infection.
Similar content being viewed by others
References
Abela-Ridder B, Sikkema R, Hartskeerl RA (2010) Estimating the burden of human leptospirosis. Int J Antimicrob Agents 36:S5–S7
Adler B, Moctezuma AP (2010) Leptospira and leptospirosis. Rev Vet Microbiol 140:287–296
Bharti AR, Nally JE, Ricaldi JN, Matthias MA, Diaz MM, Levett MA, Levett PN, Gilman RH, Willig MR, Gotuzzo E, Vinetz JM (2003) Leptospirosis: a zoonotic disease of global importance. Lancet Infect Dis 3:757–771
Bolin CA, Prescott JF (1999) Leptospirosis. In: Howard JL, Smith RA (eds) Current Veterinary Therapy, vol 1, 4th edn. Saunders, Philadelphia, pp 352–357
Bours MJL, Swennen ELR, Di Virgilio F, Cronstein BN, Dagnelie PC (2006) Adenosine 5′- triphosphate and adenosine as endogenous signaling molecules in immunity and inflammation. Pharmacol Ther 112:358–404
Cohen J (2002) The immunopathogenesis of sepsis. Nature 420:885–891
Cullor JS (1992) Shock attributable to bacteremia and endotoxemia in cattle: clinical and experimental findings. J Am Vet Med Assoc 200(12):1894–1902
Di Virgilio F (2007) Purinergic signalling in the immune system. A brief update. Purinergic Signal 3(1–2):1–3
Edwards CN, Nicholson GD, Hassell TA, Everard CO, Callender J (1986) Thrombocytopenia in leptospirosis: the absence of evidence for disseminated intravascular coagulation. Am J Trop Med Hyg 35:352–354
Evangelista KV, Coburn J (2010) Leptospira as an emerging pathogen: a review of its biology, pathogenesis and host immune responses. Future Microbiol 9:1413–1425
Faine S, Adler B, Bolin C, Perolat P (1999) Leptospira and leptospirosis, 2nd edn. Mediscience, Melbourne
Fredholm BB, Jacobson KA, Linden J, Muller CE (2011) International Union of Basic and Clinical Pharmacology. Nomenclature and classification of adenosine receptors—an update. Pharmacol Rev 63:1–34
Hasko G, Cronstein BN (2004) Adenosine: an endogenous regulator of innate immunity. Trends Immunol 25:33–39
He P, Zhang XY, Guo XK, Hu BY, Huang XT, Yang Y, Zhao GP (2004) Identification and analysis of genes present in Leptospira interrogans serovar Lai, but absent in L. biflexa serovar Monvalerio. Acta Biochim Biophys Sin 36:832–839
Higgins R, Cousineau G (1977) The pathogenesis of Leptospirosis L. Hemorrhages in experimental leptospirosis in guinea pigs. Can J Vet Res 41(2):174–181
Kumar V, Sharma A (2009) Adenosine: an endogenous modulator of innate immune system with therapeutic potential. Eur J Pharmacol 616:7–15
Langston HP, Ke Y, Gewirtz AT, Dombrowski KE, Kapp JA (2003) Secretion of IL-2 and IFN-gamma, but not IL-4, by antigen-specific T cells requires extracellular ATP. J Immunol 170(6):2962–2970
Lohuis JACM, Verheijden JHM, Burvenich C, Van Miert ASJPAM (1988) Pathophysiological effects of endotoxins in ruminants. Vet Q 10(1):109–125
McBride AJ, Athanazio DA, Reis MG, Ko IA (2005) Leptospirosis. Curr Opin Infect Dis 18:376–386
Nicodemo AC, Duarte MI, Alves VA, Takakura CF, Santos RT, Nicodemo EL (1997) Lung lesions in human leptospirosis: microscopic, immunohistochemical, and ultrastructural features related to thrombocytopenia. Am J Trop Med Hyg 56:181–187
Nworu CS, Akah PA, Okoye FB, Esimone CO (2012) Inhibition of pro-inflammatory cytokines and inducible nitric oxide by extract of Emilia sonchifolia L. aerial parts. Immunopharmacol Immunotoxicol 34(6):925–931
Picardeau M (2013) Diagnosis and epidemiology of leptospirosis. Med Mal Infect 43:1–9
Ralevic V, Burnstock G (2003) Involvement of purinergic signalling in cardiovascular diseases. Drug News Perspect 16:133–140
Santos CX, Anjos EI, Augusto O (1999) Uric acid oxidation by peroxynitrite: multiple reactions, free radical formation, and amplification of lipid oxidation. Arch Biochem Biophys 372(2):285–294
Tonin AA, Pimentel VC, Da Silva AS, Azevedo MI, Souza VC, Wolkmer P, Rezer JF, Badke MR, Leal DB, Schetinger MR, Monteiro SG, Lopes ST (2012a) Adenosine deaminase activity in serum, erythrocytes and lymphocytes of rats infected with Leptospira Icterohaemorrhagiae. Res Vet Sci 92:197–201
Tonin AA, Azevedo MI, Da Silva AS, Costa MM, França RT, Pimentel VC, Souza VCG, Jaques JAS, Leal CAM, Badke MRT, Leal DBR, Schetinger MRC, Lopes STA (2012b) Activities of the enzymes NTPDase, 5′-nucleotidase and adenosine deaminase in platelets of rats experimentally infected with Leptospira interrogans serovar Icterohaemorrhagiae. Acta Sci Vet 40(4):1078
Voelter W, Zech K, Arnold P, Ludwig G (1980) Determination of selected pyrimidines, purines and their metabolites in serum and urine by reversed-phase ion pair chromatography. J Chromatogr 199:345–354
Wagenaar JF, Goris MG, Sakundarno MS, Gasem MH, Mairuhu AT, Knuif MD, Ten Cate H, Hartskeerl R, Brandjes DP, Van Gorp EC (2007) What role do coagulation disorders play in the pathogenesis of leptospirosis? Trop Med Int Health 12:111–122
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Tonin, A.A., Da Silva, A.S., Jaques, J.A. et al. Changes in serum levels of purines in an experimental infection by Leptospira interrogans serovar Icterohaemorrhagiae. Comp Clin Pathol 24, 721–725 (2015). https://doi.org/10.1007/s00580-014-1970-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00580-014-1970-2