Suchergebnisse

Chagas disease caused by Trypanosoma cruzi is a neglected disease that affects about 7 million people in Latin America, recently emerging on other continents due to migration. As infection in mice is characterized by depletion of plasma L-arginine, the effect on infection outcome was tested in mice with or without L-arginine supplementation and treatment with 1400W, a specific inhibitor of inducible nitric oxide synthase (iNOS). We found that levels of L-arginine and citrulline were reduced in the heart and plasma of infected mice, whereas levels of asymmetric dimethylarginine, an endogenous iNOS inhibitor, were higher. Moreover, L-arginine supplementation decreased parasitemia and heart parasite burden, improving clinical score and survival. Nitric oxide production in heart tissue and plasma was increased by L-arginine supplementation, while pharmacological inhibition of iNOS yielded an increase in parasitemia and worse clinical score. Interestingly, electrocardiograms improved in mice supplemented with L-arginine, suggesting that it modulates infection and heart function and is thus a potential biomarker of pathology. More importantly, L-arginine may be useful for treating T. cruzi infection, either alone or in combination with other antiparasitic drugs. ; ªFondo de Investigaciones Sanitariasº (PI12/00289); ªUniversidad Autónoma de Madridº and ªBanco de Santanderº (CEAL-AL/2015-12);ªMinisterio de Economía y competitividadº SAF2015-63868-R (MINECO/FEDER); by (MF) grants from ªMinisterio de Ciencia e Innovaciónº (SAF2010-17833); SAF2016-75988-R (MINECO/FEDER) ªRed de Investigación de Centros de Enfermedades Tropicalesº (RICET RD12/0018/0004); European Union (HEALTH-FE-2008-22303, ChagasEpiNet); AECID Cooperation with Argentina (A/025417/09 and A/031735/10), Comunidad de Madrid (S-2010/BMD-2332) and ªFundación Ramón Arecesº. ; Peer Reviewed

Chagas disease caused by Trypanosoma cruzi is a neglected disease that affects about 7 million people in Latin America, recently emerging on other continents due to migration. As infection in mice is characterized by depletion of plasma L-arginine, the effect on infection outcome was tested in mice with or without L-arginine supplementation and treatment with 1400W, a specific inhibitor of inducible nitric oxide synthase (iNOS). We found that levels of L-arginine and citrulline were reduced in the heart and plasma of infected mice, whereas levels of asymmetric dimethylarginine, an endogenous iNOS inhibitor, were higher. Moreover, L-arginine supplementation decreased parasitemia and heart parasite burden, improving clinical score and survival. Nitric oxide production in heart tissue and plasma was increased by L-arginine supplementation, while pharmacological inhibition of iNOS yielded an increase in parasitemia and worse clinical score. Interestingly, electrocardiograms improved in mice supplemented with L-arginine, suggesting that it modulates infection and heart function and is thus a potential biomarker of pathology. More importantly, L-arginine may be useful for treating T. cruzi infection, either alone or in combination with other antiparasitic drugs. ; This work was supported by (NG) grants from "Fondo de Investigaciones Sanitarias" (PI12/ 00289); "Universidad Autónoma de Madrid" and "Banco de Santander" (CEAL-AL/2015- 12); "Ministerio de Economía y competitividad" SAF2015-63868-R (MINECO/FEDER); by (MF) grants from "Ministerio de Ciencia e Innovación" (SAF2010-17833);grants from "Ministerio de Ciencia e Innovación" (SAF2010-17833); SAF2016-75988-R (MINECO/FEDER) "Red de Investigación de Centros de Enfermedades Tropicales" (RICET RD12/0018/ 0004); European Union (HEALTH-FE-2008-22303, ChagasEpiNet); AECID Cooperation with Argentina (A/025417/09 and A/031735/10), Comunidad de Madrid (S-2010/BMD-2332) and "Fundación Ramón Areces"