Treatment with low doses of aspirin during chronic phase of experimental Chagas’ disease increases oesophageal nitrergic neuronal subpopulation in mice

Patients with Chagas’ disease may develop dysfunctions of oesophageal and colonic motility resulting from the degeneration or loss of the myenteric neurons of the enteric nervous system. Studies have shown that the use of aspirin, also known as acetylsalicylic acid (ASA), influences the pathogenesis of the disease. However, this remains controversial. The aim of this study was to evaluate the consequences of treatment with low doses of aspirin during the chronic phase of Chagas’ disease on oesophageal function. Twenty male Swiss mice, 60 days of age, were used. The animals were infected with Y strain of Trypanosoma cruzi, injected intraperitoneally. Aspirin was given at a dose of 50 mg/kg to some of the infected animals, from the 55th to 63rd day after inoculation on consecutive days, and from the 65th to 75th day on alternate days. We investigated food passage of time, wall structure and nitrergic neuronal population of the distal oesophagus. Our data revealed that the use of low doses of aspirin in chronic Chagas’ disease caused an increase in the number of nitrergic neurons and partially prevented hypertrophy of the oesophagus. In addition, the aspirin administration impeded Chagas' diseases associated changes in intestinal transit time. Thus treatment with aspirin in the chronic phase of Chagas’ disease changes the natural history of the disease and raises the possibility of using it as a new therapeutic approach to the treatment of this aspect of Chagas' disease pathology.

[1]  P. Pinge-Filho,et al.  Myenteric neuroprotective role of aspirin in acute and chronic experimental infections with Trypanosoma cruzi , 2017, Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society.

[2]  P. Pinge-Filho,et al.  Aspirin prevents atrophy of esophageal nitrergic myenteric neurons in a mouse model of chronic Chagas disease. , 2016, Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus.

[3]  D. Saur,et al.  Dominant role of interstitial cells of Cajal in nitrergic relaxation of murine lower oesophageal sphincter , 2015, The Journal of physiology.

[4]  A. Jammal,et al.  BLOOD VESSELS IN GANGLIA IN HUMAN ESOPHAGUS MIGHT EXPLAIN THE HIGHER FREQUENCY OF MEGAESOPHAGUS COMPARED WITH MEGACOLON , 2014, Revista do Instituto de Medicina Tropical de Sao Paulo.

[5]  R Core Team,et al.  R: A language and environment for statistical computing. , 2014 .

[6]  Hyun-Jung Cho,et al.  The enteric nervous system and gastrointestinal innervation: integrated local and central control. , 2014, Advances in experimental medicine and biology.

[7]  J. Bornstein,et al.  Properties of cholinergic and non-cholinergic submucosal neurons along the mouse colon , 2013, Autonomic Neuroscience.

[8]  A. Molina-Berríos,et al.  Protective Role of Acetylsalicylic Acid in Experimental Trypanosoma cruzi Infection: Evidence of a 15-epi-Lipoxin A4-Mediated Effect , 2013, PLoS neglected tropical diseases.

[9]  S. Adad,et al.  An imbalance between substance P and vasoactive intestinal polypeptide might contribute to the immunopathology of megaesophagus after Trypanosoma cruzi infection. , 2013, Human pathology.

[10]  M. Gastellu-Etchegorry,et al.  [Chagas disease (American trypanosomiasis) in France]. , 2012, Medecine et maladies infectieuses.

[11]  P. König,et al.  Nitric oxide-sensitive guanylyl cyclase is dispensable for nitrergic signaling and gut motility in mouse intestinal smooth muscle. , 2011, Gastroenterology.

[12]  C. Hermes-Uliana,et al.  Chronic infection with Toxoplasma gondii causes myenteric neuroplasticity of the jejunum in rats , 2011, Autonomic Neuroscience.

[13]  L. Weiss,et al.  Aspirin Treatment of Mice Infected with Trypanosoma cruzi and Implications for the Pathogenesis of Chagas Disease , 2011, PloS one.

[14]  W. Neuhuber,et al.  Partial, selective survival of nitrergic neurons in chagasic megacolon , 2010, Histochemistry and Cell Biology.

[15]  C. Bern,et al.  Chagas disease in Spain, the United States and other non-endemic countries. , 2010, Acta tropica.

[16]  E. Liberti,et al.  Effects of perinatal protein deprivation and recovery on esophageal myenteric plexus. , 2010, World journal of gastroenterology.

[17]  E. C. D. Almeida,et al.  Atrophy of the Nitrergic Myenteric Neurons in the Descending Colon Rats Submitted to Protein and Vitamin Deficiency , 2009 .

[18]  L. Castellano,et al.  [Role of nitric oxide in the development of cardiac lesions during the acute phase of experimental infection by Trypanosoma cruzi]. , 2009, Revista da Sociedade Brasileira de Medicina Tropical.

[19]  Y. Nojyo,et al.  Interstitial cells of Cajal are innervated by nitrergic nerves and express nitric oxide–sensitive guanylate cyclase in the guinea-pig gastrointestinal tract , 2008, Neuroscience.

[20]  T. Araújo-Jorge,et al.  Applicability of the use of charcoal for the evaluation of intestinal motility in a murine model of Trypanosoma cruzi infection , 2008, Parasitology Research.

[21]  L. Rizzo,et al.  E¡ects of cyclooxygenase inhibitors on parasite burden, anemia and oxidative stress in murineTrypanosomacruzi infection , 2007 .

[22]  F. Chan,et al.  Prevention of non‐steroidal anti‐inflammatory drug gastrointestinal complications – review and recommendations based on risk assessment , 2004, Alimentary pharmacology & therapeutics.

[23]  T. Powley,et al.  Aging of the myenteric plexus: neuronal loss is specific to cholinergic neurons , 2003, Autonomic Neuroscience.

[24]  AndreasFriebe,et al.  Regulation of Nitric Oxide-Sensitive Guanylyl Cyclase , 2003 .

[25]  Jian-xiang Liu,et al.  Esophageal dysmotility and the change of synthesis of nitric oxide in a feline esophagitis model. , 2002, Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus.

[26]  Nzerue Cm The coxibs, selective inhibitors of cyclooxygenase-2. , 2001 .

[27]  R. Tarleton Parasite persistence in the aetiology of Chagas disease. , 2001, International journal for parasitology.

[28]  Diane Lambert,et al.  Zero-inflacted Poisson regression, with an application to defects in manufacturing , 1992 .

[29]  E. R. Lopes,et al.  Contribuição ao estudo da anatomia patológica do megaesôfago chagásico , 1991 .

[30]  E. Chapadeiro,et al.  [Pathological anatomy of chagasic megaesophagus]. , 1991, Revista do Instituto de Medicina Tropical de Sao Paulo.

[31]  Philip Heidelberger,et al.  Simulation Run Length Control in the Presence of an Initial Transient , 1983, Oper. Res..

[32]  M. Cisternino,et al.  Antiinflammatory drugs and gastric emptying. A comparison between acetylsalicylic acid and carprofen. , 1982, Arzneimittel-Forschung.

[33]  F. Köberle Chagas' disease and Chagas' syndromes: the pathology of American trypanosomiasis. , 1968, Advances in parasitology.