Effect ofCrotalus viridis viridissnake venom on the ultrastructure and intracellular survival ofTrypanosoma cruzi

Abstract

SUMMARYChagas' disease, caused byTrypanosoma cruzi, affects 16–18 million people in Central and South America. Patient treatment is based on drugs that have toxic effects and limited efficacy. Therefore, new chemotherapeutic agents need to be developed. Snake venoms are sources of natural compounds used in various medical treatments. We observed thatCrotalus viridis viridisvenom was effective against all developmental forms ofT. cruzi.Ultrastructural analysis revealed swelling of mitochondria, blebbing and disruption of the plasma membrane, loss of cytoplasm components and morphological changes of the cell. Staining with propidium iodide and rhodamine 123 confirmed the observed alterations in the plasma and mitochondrial membranes, respectively. The effects of the venom on the parasite intracellular cycle were also analysed. Pre-infected LLC-MK2cells incubated withCvvvenom showed a 76–93% reduction in the number of parasites per infected cell and a 94–97·4% reduction in the number of parasites per 100 cells after 96 h of infection. Free trypomastigotes harvested from the supernatants ofCvvvenom-treated cells were incapable of initiating a new infection cycle. Our data demonstrate thatCvvvenom can access the host cell cytoplasm at concentrations that cause toxicity only to the amastigote forms ofT. cruzi, and yields altered parasites with limited infective capacity, suggesting the potential use ofCvvvenom in Chagas' disease chemotherapy.