Dual chemotherapy with benznidazole at suboptimal dose plus curcumin nanoparticles mitigates Trypanosoma cruzi-elicited chronic cardiomyopathy

• Published in: Parasitology international 2021-04, Vol.81, p.102248-102248, Article 102248
• Main Authors: Hernández, Matías, Wicz, Susana, Pérez Caballero, Eugenia, Santamaría, Miguel H., Corral, Ricardo S.
• Format: Article
• Language: English
• Subjects: Benznidazole; Chagas disease; Chronic cardiomyopathy; Curcumin; Oral treatment; Trypanosoma cruzi
• ISSN: 1383-5769; 1873-0329
• DOI: 10.1016/j.parint.2020.102248

Curcumin (Cur) is a natural polyphenolic flavonoid isolated from the rhizomes of Curcuma longa. Its anti-inflammatory and cardioprotective properties are increasingly considered to have beneficial effects on the progression of cardiomyopathy associated with Chagas disease, caused by Trypanosoma cruzi. However, the Cur therapeutic limitation is its bioavailability and new Cur nanomedicine formulations are developed to overcome this obstacle. In this research, we provide evidence showing that oral therapy with a suboptimal dose of the standard parasiticidal drug benznidazole (BZ) in combination with Cur-loaded nanoparticles is capable of reducing myocardial parasite load, cardiac hypertrophy, inflammation and fibrosis in mice with long-term infection by T. cruzi. Treatment with BZ plus Cur was highly effective in downregulating myocardial expression of proinflammatory cytokines/chemokines (IL-1β, TNF-α, IL-6, CCL5), and the level/activity of matrix metalloproteinases (MMP-2, MMP-9) and inducible enzymes (cyclooxygenase, nitric oxide synthase) implicated in leukocyte recruitment and cardiac remodeling. Oral administration of a Cur-based nanoformulation displays potential as a complementary strategy to the conventional BZ chemotherapy in the treatment of chronic Chagas heart disease. [Display omitted] •Long-lasting Trypanosoma cruzi infection is a frequent cause of severe cardiomyopathy.•Conventional treatment with benznidazole is inefficient and provokes adverse effects.•We tested a combination of benznidazole at low dose with curcumin nanoparticles.•Benznidazole plus nanocurcumin reduces heart parasitism, inflammation and fibrosis.•Dual therapy strategy displays potential for treating chronic Chagas heart disease.