Role of endothelin receptors in the control of central nervous system parasitism in Trypanosoma cruzi infection in rats.
Endothelin has been implicated in the pathogenesis of experimental and human Chagas disease. In the present study, we investigated whether the treatment with bosentan, an antagonist of both ET(A)/ET(B) endothelin receptors, modified parasite load and inflammation in the central nervous system (CNS) of Trypanosomacruzi-infected rats. The cerebellum was the most affected region in the CNS with marked parasitism and inflammation. Treatment with bosentan enhanced parasitemia and CNS parasitism, but control of infection was eventually attained. There was also an increase in the levels of the cytokines TNF-alpha, IL-10, IFN-gamma, CCL2/MCP-1, CCL3/MIP-1alpha and CCL5/RANTES in the brain of infected animals at days 9, 13 and 18 after infection. Overall, bosentan has some effects on the expression of certain cytokines and this may be related to the initial enhanced parasite load. Altogether, our data suggest that endothelin action via ET(A) and ET(B) receptors may play a role in the initial resistance of the CNS to T. cruzi infection in rats.
Rachid
Milene A
MA
Departamento de Patologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31270901, Belo Horizonte, MG, Brazil. milenerachid@ig.com.br
Teixeira
Antônio L
AL
Barcelos
Lucíola S
LS
Machado
Conceição R S
CR
Chiari
Egler
E
Tanowitz
Herbert B
HB
Camargos
Elizabeth R S
ER
Teixeira
Mauro M
MM
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use; D000977:Antiparasitic Agents / Q000494:pharmacology / Q000627:therapeutic use; D000077300:Bosentan; D001921:Brain / Q000187:drug effects / Q000276:immunology / Q000469:parasitology; D014355:Chagas Disease / Q000150:complications*; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004660:Encephalitis / Q000188:drug therapy* / Q000469:parasitology* / Q000503:physiopathology; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000037:antagonists & inhibitors / Q000378:metabolism; D007113:Immunity, Innate / Q000187:drug effects / Q000276:immunology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017466:Receptors, Endothelin / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome; D014349:Trypanosoma cruzi / Q000276:immunology*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D000959:Antihypertensive Agents; D000977:Antiparasitic Agents; D016207:Cytokines; D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D017466:Receptors, Endothelin; D013449:Sulfonamides; D000077300:Bosentan