Evaluation of oxidative metabolism in Trypanosoma cruzi strains treated with diamines of ferrocene

• Grant number: 11/06525-2
• Support Opportunities: Regular Research Grants
• Start date: July 01, 2011
• End date: June 30, 2013
• Field of knowledge: Physical Sciences and Mathematics - Chemistry
• Principal Investigator: Regina Maria Barretto Cicarelli
• Grantee: Regina Maria Barretto Cicarelli
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Chagas' disease, caused by Trypanosoma cruzi, affects millions of people in Latin America. For the treatment of disease, only two drugs are currently available, nifurtimox (5-nitrofuran), which is not used in Brazil, and benznidazole (2-nitroimidazole) which production was reduced. However, for both drugs, their actions are limited, since it depends on the stage of disease, physical conditions of the host's susceptibility and genetic variability of the strain. Thus, the search for new drugs remains a challenge for Brazilian science, along with understanding the mechanism of resistance to trypanocidal drugs. Some studies report an increase in the production of enzymes that act in cellular defense, which probably could be responsible for the resistance of certain strains of the parasite. These enzymes have important functions in the survival and growth of parasites: superoxide dismutase (SOD), which eliminates metalloenzyme superoxide radicals to convert them into hydrogen peroxide and molecular oxygen, old yellow enzyme (OYE), which is an NADPH flavin oxidoreductase and can be involved in the reduction of trypanocidal substances, and peroxiredoxin (PRX), which catalyzes the reduction of peroxides. The mechanism of resistance to drugs used against T. cruzi is poorly known, but some experiments have reported that parasites resistant to benznidazole overexpress some proteins when exposed to that substance. The parasites have a high diversity of morphological, genetic, behavioral and clinical outcomes, conferring pathogenicity and parasitemia different in each strain, which complicates the treatment of disease. Recently, the lab team guiding the cloned and expressed the recombinant protein gene of peroxiredoxin (PRX) T. cruzi, which after purification was used in the production of antibodies that revealed by Western blot, differences in the expression of the enzyme in the parasite strains in untreated and treated with benznidazole (manuscript in preparation). Thus, this project aims to clone and express the genes responsible for two other enzymes SOD and OYE, which also produces antibodies against the respective recombinant proteins in order to verify, by the same Western blot, changes in its level of expression in strains treated or not with diamines of ferrocene, which showed intense activity tripnocida. The expression of PRX protein will also be evaluated. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

KOHATSU, ANDREA A. N.; SILVA, FLAVIA A. J.; FRANCISCO, ACACIO I.; RIMOLDI, ALINE; SILVA, MARCO T. A.; VARGAS, MARIA D.; DA ROSA, JOAO A.; CICARELLI, REGINA M. B.. Differential expression on mitochondrial tryparedoxin peroxidase (mTcTXNPx) in Trypanosoma cruzi after ferrocenyl diamine hydrochlorides treatments. Brazilian Journal of Infectious Diseases, v. 21, n. 2, p. 125-132, MAR-APR 2017. (11/06525-2)