Skip to main content
SpringerLink
Log in

Increased in cyclooxygenase—2 immunoreactivity and DNA damage in hippocampus of rats infected by Trypanosoma evansi

  • Original Article
  • Published:
Comparative Clinical Pathology Aims and scope Submit manuscript

Abstract

Cyclooxygenase-2 (COX-2) is one of the two isoforms of COX producing prostaglandins derived from arachidonic acid. COX-2 is the inducible isoform expressed in many cell types in response to cytokines and pro-inflammatory molecules. In brain, COX-2 is frequently associated with pro-inflammatory activities, and its increase is related to neurodegenerative processes in acute and chronic diseases. Thus, the aim of this study was to evaluate the COX-2 immunoreactivity and the frequency damage caused by T. evansi infection on days 5 and 15 post-infection (PI) in hippocampus cells, as well as the relationship with behavioral alterations. Decreased (p < 0.05) memory was observed in infected rats on days 5 and 15 PI. An increase in COX-2 immunoreactivity was observed in hippocampus of infected rats on day 15 PI (p < 0.05). Similarly, there was an increase in the frequency of damage in hippocampus of infected rats on days 5 and 15 PI (p < 0.05). This increment on COX-2 immunoreactivity may be associated with pro-inflammatory activities. Such activities are related to neurodegenerative alterations, as observed in histopathological analyses, and contribute to neurological pathophysiology of trypanosomosis.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Abdalla GK, Faria GEL, Silva KT, Castro ECC, Reis MA, Michelin MA (2008) Trypanosoma cruzi: the role of PGE2 in immune response during the acute phase of experimental infection. Exp Parasitol 118:514–521

    Article  CAS  PubMed  Google Scholar 

  • Baldissera MD, Da Silva AS, Oliveira CB, Vaucher RA, Santos RCV, Duarte T, Duarte MMMF, França RT, Lopes STA, Raffin RP, Boligon AA, Athayde ML, Stefani LM, Monteiro SG (2014) Effect of tea tree oil (Melaleuca alternifolia) on the longevity and immune response of rats infected with Trypanosoma evansi. Res Vet Sci 96:501–506

    Article  CAS  PubMed  Google Scholar 

  • Baldissera MD, Rech VC, Da Silva AS, Nishihira VSK, Ianiski FR, Gressler LT, Grando TH, Vaucher RA, Schwertz CI, Mendes RE, Monteiro SG (2015) Relationship between behavioral alterations and activities of adenylate kinase and creatine kinase in brain of rats infected by Trypanosoma evansi. Exp Parasitol 151–152:96–102

    Article  PubMed  Google Scholar 

  • Beckman JS, Koppenol WH (1996) Nitric oxide, superoxide and peroxynitrite: the good, the bad, and the ugly. Am J Physiol 271:C1424–1437

    CAS  PubMed  Google Scholar 

  • Berlin D, Loeb E, Baneth G (2009) Disseminated central nervous system disease caused by Trypanosoma evansi in a horse. Vet Parasitol 161:316–319

    Article  PubMed  Google Scholar 

  • Cassano P, Hidalgo A, Burgos V, Adris S, Argibay P (2006) Hippocampal upregulation of the cyclooxygenase-2 gene following neonatal clomipramine treatment (a model of depression). Pharmacogenomics J 6:381–387

    Article  CAS  PubMed  Google Scholar 

  • Colpo CB, Monteiro SG, Stainki DR, Colpo ETB, Henriques GB (2005) Natural infection by Trypanosoma evansi in dogs. Cienc Rural 35:717–719

    Article  Google Scholar 

  • Da Silva AS, Doyle RL, Monteiro SG (2006) Métodos de contenção e confecção de esfregaço sanguíneo para pesquisa de hemoparasitas em ratos e camundongos. FMVZA 13:83–87

    Google Scholar 

  • Da Silva AS, Spanevello R, Stefanello N, Wolkmer P, Costa MM, Zanette RA, Lopes STA, Santurio JM, Schetinger MRC, Monteiro SG (2010) Influence of Trypanosoma evansi in blood, plasma, and brain cholinesterase of experimentally infected cats. Res Vet Sci 88:281–284

    Article  PubMed  Google Scholar 

  • Da Silva AS, Monteiro SG, Gonçalves JF, Spanevello R, Oliveira CB, Costa MM, Jaques JAS, Morsch VM, Schetinger MRC, Mazzanti CM, Lopes STA (2011) Acetylcholinesterase activity and lipid peroxidation in the brain and spinal cord of rats infected with Trypanosoma evansi. Vet Parasitol 175:237–244

    Article  PubMed  Google Scholar 

  • Dantzer R, O’Connor JC, Freund GG, Johnson RW, Kelley KW (2008) From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci 9:46–56

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • De Oliveira LRC, Cezário GAG, De Lima CRG, Nicolete VC, Peresi E, De Síbio MT, Picka MCM, Calvi AS (2011) DNA damage and nitric oxide production in mice following infection with Leishmania chagasi. Mutat Res-Gen Tox En 723:177–181

    Article  Google Scholar 

  • Desquesnes M, Dargantes A, Lai DH, Lun ZR, Holzmuller P, Jittapalapong S (2013) Trypanosoma evansi and Surra: a review and perspectives on transmission, epidemiology and control, impact, and zoonotic aspects. Biomed Res Int 2013:321237

    PubMed  PubMed Central  Google Scholar 

  • Dizdaroglu M (1994) Chemical determination of oxidative DNA damage by gas chromatography–mass spectrometry. Methods Enzymol 234:3–16

    Article  CAS  PubMed  Google Scholar 

  • Galecki P, Talarowska M, Bobinska K, Szemraj J (2015) COX-2 gene expression is correlated with cognitive function in recurrent depressive disorder. Psychiatry Res 215:488–490

    Article  Google Scholar 

  • Gao W, Pereira MA (2002) Interleukin–6 is required for parasite specific for parasite response and host resistance to Trypanosoma cruzi. Int J Parasitol 32:167–170

    Article  CAS  PubMed  Google Scholar 

  • Heleniak E, O’Desky I (1999) Histamine and prostaglandins in schizophrenia: revisited. Med Hypotheses 52:37–42

    Article  CAS  PubMed  Google Scholar 

  • Ivanov AI, Romanovsky AA (2004) Prostaglandin E2 as a mediator of fever: synthesis and catabolism. Front Biosci 9:1977–1993

    Article  CAS  PubMed  Google Scholar 

  • Joshi PP, Shegokar VR, Powar RM, Herder S, Katti R, Salkar HR, Dani VS, Bhargava A, Jannin J, Truc P (2005) Human trypanosomosis caused by Trypanosoma evansi in India: the first case report. J Trop Med Hyg 73:491–495

    Google Scholar 

  • Malvezi AD, Panis C, da Silva RV, de Freitas RC, Lovo-Martins MI, Tatakihara VLH, Zanluqui NG, Cunha Neto E, Goldenberg S, Bordignon J, Yamada-Ogatta SF, Martins-Pinge MC, Cecchini R, Pinge-Filho P (2014) Inhibition of cyclooxygenase-1 and cyclooxygenase-2 impairs Trypanosoma cruzi entry into cardiac cells and promotes differential modulation of the inflammatory response. Antimicrob Agents Chemother 58:6157–6164

    Article  PubMed  PubMed Central  Google Scholar 

  • Martino G, Adorini L, Rieckamnn P, Hillert J, Kallmann B, Comi G, Filippi M (2002) Inflammation in multiple sclerosis: the good, the bad, and the complex. Lancet Neurol 1:499–509

    Article  PubMed  Google Scholar 

  • Melnikova T, Savonenko A, Wang Q, Liang X, Hand T, Wu L, Kaufmann WE, Vehmas A, Andreasson KI (2006) Cycloxygenase-2 activity promotes cognitive deficits but not increased amyloid burden in a model of Alzheimer’s disease in a sex-dimorphic pattern. Neuroscience 141:1149–1162

    Article  CAS  PubMed  Google Scholar 

  • Minghetti L (2014) Cyclooxygenase-2 (COX-2) in inflammatory and degenerative brain diseases. J Neuropathol Exp Neurol 63:901–910

    Article  Google Scholar 

  • Mohan S, Epstein JB (2003) Carcinogenesis and cyclooxigenase: the potential role of COX-2 inhibition in upper aerodigestive tract cancer. Oral Oncol 39:537–546

    Article  CAS  PubMed  Google Scholar 

  • Moraes KCM, Diniz LF, Bahia MT (2015) Role of cyclooxygenase-2 in Trypanosoma cruzi survival in the early stages of parasite host-cell interaction. Mem Inst Oswaldo Cruz 110:181–191

    Article  PubMed  PubMed Central  Google Scholar 

  • Okazaki K, Ishii Y, Kitamura Y, Maruyama S, Umemura T, Miyauchi M, Yamagishi M, Imazawa T, Nishikawa A, Yoshimura Y, Nakazawa H, Hirose H (2006) Dose-dependent promotion of rat for estomach carcinogenesis by combined treatment with sodium nitrite and ascorbic acid after initiation with N-methyl-N-nitro-N-nitrosoguanidine: possible contribution of nitric oxide-associated oxidative DNA damage. Cancer Sci 97:175–182

    Article  CAS  PubMed  Google Scholar 

  • Oliveira CB, Spanevello R, Da Silva AS, Souza VCG, Pimentel VC, Thomé GR, Schetinger MR, Lopes STA, Leal DBR, Monteiro SG (2011) Trypanosoma evansi: activities of adenine nucleotide degradation enzymes in cerebral cortex of infected rats. Exp Parasitol 128:225–229

    Article  CAS  PubMed  Google Scholar 

  • Pasinetti GM, Aisen PS (1998) Cyclooxygenase-2 expression is increased in frontal cortex of Alzheimer’s disease brain. Neuroscience 87:319–24

    Article  CAS  PubMed  Google Scholar 

  • Reis MM, Higuchi ML, Benvenuti LA, Aiello VD, Gutierrez PS, Bellotti G, Pileggi F (1997) An in situ quantitative immunohistochemical study of cytokines and IL-2R in chronic human chagasic myocarditis: correlation with the presence of myocardial T. Cruzi antigens. Clin Immunol Immunopathol 83:165–172

    Article  CAS  PubMed  Google Scholar 

  • Ribeiro DA, Calvi SA, Picka MM, Persi E, de Carvalho TB, Caetano PK, Nagoshi LR, Lima CRG, Machado JM, Salvadori DMF (2007) DNA damage and nitric oxide synthesis in experimentally infected balb/c mice with Trypanosoma cruzi. Exp Parasitol 116:296–301

    Article  CAS  PubMed  Google Scholar 

  • Rodrigues A, Fighera RA, Souza TM, Schild AL, Soares MP, Milano J, Barros CSL (2005) Outbreaks of trypanosomiasis in horses by Trypanosoma evansi in the state of Rio Grande do Sul, Brazil: epidemiological, clinical, hematological, and pathological aspects. Pesqui Vet Bras 25:239–249

    Article  Google Scholar 

  • Rodrigues A, Fighera RA, Souza TM, Schild AL, Barros CS (2009) Neuropathology of naturally occurring Trypanosoma evansi infection in horses. Vet Pathol 46:251–258

    Article  CAS  PubMed  Google Scholar 

  • Romero-Calvo I, Ocon B, Martinez-Moya P, Suarez MD, Zarzuelo A, Martinez-Augustin O, de Medina FS (2010) Reversible ponceau staining as a loading control alternative to actin in Western blots. Anal Biochem 401:318–320

    Article  CAS  PubMed  Google Scholar 

  • Rose JW, Hill KE, Watt HE, Carlson NG (2004) Inflammatory cell expression of cyclooxygenase-2 in the multiple sclerosis lesion. J Neuroimmunol 149:40–49

    Article  CAS  PubMed  Google Scholar 

  • Sakaguchi M, Koseki M, Wakamatsu M, Matsumura E (2006) Effects of systemic administration of β-casomorphin-5 on learning and memory in mice. Eur J Pharmacol 530:81–87

    Article  CAS  PubMed  Google Scholar 

  • Shaw NK, Commins S, O’Mara SM (2003) Deficits in spatial learning and synaptic plasticity induced by the rapid and competitive broad-spectrum cyclooxygenase inhibitor ibuprofen are reversed by increasing endogenous brain derived neurotrophic factor. Eur J Neurosci 17:2438–2446

    Article  PubMed  Google Scholar 

  • Teismann P, Tieu K, Choi DK, Wu DC, Naini A, Hunot S, Vila M, Jackson-Lewis V, Przedborski S (2003) Cyclooxygenase-2 is instrumental in Parkinson’s disease neurodegeneration. Proc Natl Acad Sci U S A 100:5473–5478

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tice RR, Agurell D, Anderson D, Burlinson B, Hartmann A, Kobayashi H, Miyamae Y, Rojas E, Ryu JC, Sasaki YF (2000) Single cell gel/comet assay: guidelines for in vitro and in vivo genetic toxicology testing. Environ Mol Mutagen 35:206–221

    Article  CAS  PubMed  Google Scholar 

  • Trevisan G, Hoffmeister C, Rossato MF, Oliveira SM, Silva MA, Ineu RP, Guerra GP, Materazzi S, Camilla Fusi C, Nassini R, Geppetti P, Ferreira J (2013) Transient receptor potential ankyrin receptor stimulation by hydrogen peroxide is critical to trigger pain during monosodium urate-induced inflammation in rodents. Arthritis Rheum 65:2984–2995

    Article  CAS  PubMed  Google Scholar 

  • Tuntasuvan D, Mimapan S, Sarataphan N, Trongwongsa L, Intraraksa R, Luckins AG (2000) Detection of Trypanosoma evansi in brains of the naturally infected hog deer by immunohistochemistry. Vet Parasitol 87:223–230

    Article  CAS  PubMed  Google Scholar 

  • Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J (2007) Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 39:44–84

    Article  CAS  PubMed  Google Scholar 

  • Vane JR, Botting RM (1998) Anti-inflammatory drugs and their mechanism of action. Inflamm Res 47:S78–S87

    Article  CAS  PubMed  Google Scholar 

  • Vilar-Pereira G, Silva AA, Pereira IR, Silva RR, Moreira OC, de Almeida LR, de Souza AS, Rocha MS, Lannes-Vieira J (2012) Trypanosoma cruzi-induced depressive-like behavior is independent of meningoencephalitis but responsive to parasiticide and TNF-targeted therapeutic interventions. Brain Behav Immun 26:1136–1149

    Article  CAS  PubMed  Google Scholar 

  • Wolkmer P, Paim FC, Da Silva CB, Gai BM, Carvalho FB, Da Souza ACG, Da Rosa MM, Da Silva AS, Pereira PR, Lopes STA, Nogueira CW, Rubin MA, Monteiro SG, Mazzanti CM (2013) Trypanosoma evansi infection impairs memory, increases anxiety behavior and alters neurochemical parameters in rats. Parasitology 140:432–1441

    Article  Google Scholar 

  • Ye F, Wu J, Dunn T, Yi J, Tong X, Zhang D (2004) Inhibition of ciclooxigenase-2 activity in head and neck cancer cells by genistein. Cancer Lett 211:39–46

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Microbiology and Parasitology, Universidade Federal de Santa Maria (UFSM), Santa Maria, RS, Brazil

    Matheus D. Baldissera, Mariângela F. de Sá, Carine F. Souza & Silvia G. Monteiro

  2. Laboratory of Cell Culture, Centro Universitário Franciscano, Santa Maria, RS, Brazil

    Michele R. Sagrillo, Christopher P. Posser, Gerson Fernandes de Brum, Diulle Spat Peres, Adriana L. B. De Mello & Mirian Ferrão

  3. Laboratory of Molecular Biology, Centro Universitário Franciscano, Santa Maria, RS, Brazil

    Luis R. Peroza

  4. Department of Animal Science, Universidade do Estado de Santa Catarina (UDESC), Chapecó, SC, Brazil

    Aleksandro S. da Silva

Authors
  1. Matheus D. Baldissera
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michele R. Sagrillo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mariângela F. de Sá
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Luis R. Peroza
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Christopher P. Posser
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Gerson Fernandes de Brum
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Diulle Spat Peres
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Adriana L. B. De Mello
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Mirian Ferrão
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Carine F. Souza
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Aleksandro S. da Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Silvia G. Monteiro
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Matheus D. Baldissera.

Ethics declarations

Ethics committee

The procedures were approved by the Animal Welfare Committee of Universidade do Estado de Santa Catarina under number 01.27.14.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Baldissera, M.D., Sagrillo, M.R., de Sá, M.F. et al. Increased in cyclooxygenase—2 immunoreactivity and DNA damage in hippocampus of rats infected by Trypanosoma evansi . Comp Clin Pathol 25, 585–591 (2016). https://doi.org/10.1007/s00580-016-2235-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00580-016-2235-z

Keywords

Search

Navigation