The β-blocker carvedilol and the benznidazole modulate the cardiac immune response in the acute infection induced by Colombian strain of the Trypanosoma cruzi

Abstract

BACKGROUND The infection led by Trypanosoma cruzi persists in mammalian tissues causing an inflammatory imbalance. Carvedilol (Cv), a non-selective beta blocker drug indicated to treat heart failure and antihypertensive has shown to promote antioxidant and immunomodulatory properties which might improve the inflammation induced by T. cruzi. OBJECTIVES Evaluate the role of Cv on the inflammatory response of C57BL/6 mice acutely infected with the Colombian strain of T. cruzi. METHODS Animals were infected with the Colombian strain of T. cruzi and treated with Cv (25 mg/kg/day), benznidazole (Bz) (100 mg/kg/day) or their combination. On the 28th day of infection and 23 days of treatment, the euthanasia occurred, and the heart preserved for histopathological, oxidative stress (SOD, catalase, TBARs, carbonylated proteins) and plasma (CCL2, CCL5, TNF, IL-10) analyses. Parasitaemia and survival were assessed along the infection. FINDINGS Cv decreased TBARs, but increased the mortality rate, the parasitaemia and the levels of CCL2, CCL5, catalase and the inflammatory infiltrate in the cardiac tissue. Bz led the reduction of the inflammatory infiltrate and circulating levels of oxidative stress and inflammatory mediators in the infected mice. MAIN CONCLUSIONS Our data suggest that Cv, in this experimental model using the Colombian strain of T. cruzi, caused damage to the host.

Understanding CD8+ T Cell Immunity to Trypanosoma cruzi and How to Improve It

“…Finally, unspecific therapies used to mitigate cardiovascular symptoms may also modulate immunological pathways showing an impact on disease progression [91][92][93]. Particularly, pentoxifylline (PTX), a methylxanthine phosphodiesterase inhibitor used as cardioprotective and as treatment for peripheral vascular diseases, show important effects on CD8 + T cells activated during T. cruzi infection.…”

Theracurmin Modulates Cardiac Inflammation in Experimental Model of Trypanosoma cruzi Infection

“…The present study evaluated the oral administration of Theracurmin in experimental infection with the Colombian strain by T. cruzi , characterized as being resistant to benznidazole and as promoting a high inflammatory and tissue parasitism [ 24 , 25 , 26 ]. Our findings suggest a systemic action of Theracurmin on the circulating parasites; however, there seems to be a limitation of this action in the distribution of the natural compound in the tissues.…”

“…In addition, Theracurmin was capable of reducing the muscle damage and the inflammatory mediators, culminating in a low leukocyte influx into the organs. Furthermore, it is noted that the behavioral pattern of Theracurmin is similar to the bioavailability of benznidazole, acting in the acute phase against T. cruzi and with little efficiency in the chronic phase of infection [ 24 ]. However, we do not expect its future application to eliminate T. cruzi by itself, but as a “complementary” use in association with routine chemical treatments (e.g., benznidazole, nifurtimox or other potential new compounds).…”

Notch receptor expression in Trypanosoma cruzi‐infected human umbilical vein endothelial cells treated with benznidazole or simvastatin revealed by microarray analysis

“…This finding is reinforced by the upregulation of related pathways, such as type II interferon signaling, IFN‐α/β signaling, and Toll‐like receptors. Moreover, CCL2, CXCL11, and other related chemokines were shown to be increased during infection with T. cruzi in heart and immune cells, including cardiomyocytes and macrophages, respectively (Graefe et al, 2006; Horta et al, 2018). Although the role of NLRC5 in T. cruzi infection has not been investigated, the role of Nod‐like receptors in the regulation of the inflammasome has attracted some attention due to the potential to regulate the burden of infection through innate immunity (Gurung and Kanneganti, 2016).…”