title: Susceptibility of Trypanosoma evansi to cordycepin.
abstract: Drugs, which are effective during the early stage of trypanosomosis, but poorly penetrate the blood-brain barrier, are ineffective when parasites reach the brain and cause encephalitis. In order to seek alternative treatments, the aim of this study was to test the susceptibility of T. evansi to cordycepin in vitro and in rats experimentally infected. In vitro, a significant decrease (P<0.01) in live trypanosomes in the concentrations of 5.0 and 10 μg/mL was observed 1 hour after the beginning of the study, as well as at 3, 6, 9 and 12 hours in all concentrations compared to control. Although no curative effects were observed in the in vivo assay in the majority of groups, the drug was able to maintain parasitemia at low levels, therefore increasing the longevity of rats when compared to positive control group. Rats that received cordycepin alone or in combination with adenosine deaminase inhibitor (ADA: EHNA hydrochloride), did not show trypomastigote forms of the parasite in the bloodstream 24 hours after the administration. These animals remained negative in blood smears on average for 8 days, but thereafter had a recurrence of parasitemia. Among all the infected animals, only three rats in the group treated with the combination of cordycepin (2 mg/kg) and EHNA hydrochloride (2 mg/kg) remained negative during the experimental period. The curative efficacy of 42.5% was confirmed by PCR using T. evansi-specific primers. Thus, we conclude that cordycepin has biological effect against T. evansi, as previously reported in infections by T. brucei, T. cruzi and Leishmania sp. The treatment with cordycepin, when protected by an inhibitor of ADA, can prolong the survival of T. evansi-infected rats and provide curative efficacy.
authors.affiliation: Department of microbiology and parasitology, universidade Federal de Santa Maria, Santa Maria, Brazil. aleksandro_ss@yahoo.com.br
authors.forename: Aleksandro S
authors.initials: AS
authors.lastname: Da Silva
authors.forename: Patrícia
authors.initials: P
authors.lastname: Wolkmer
authors.forename: Joao T S
authors.initials: JT
authors.lastname: Nunes
authors.forename: Marcos R K
authors.initials: MR
authors.lastname: Duck
authors.forename: Camila B
authors.initials: CB
authors.lastname: Oliveira
authors.forename: Lucas T
authors.initials: LT
authors.lastname: Gressler
authors.forename: Marcio M
authors.initials: MM
authors.lastname: Costa
authors.forename: Régis A
authors.initials: RA
authors.lastname: Zanette
authors.forename: Cinthia M
authors.initials: CM
authors.lastname: Mazzanti
authors.forename: Sonia T A
authors.initials: ST
authors.lastname: Lopes
authors.forename: Silvia G
authors.initials: SG
authors.lastname: Monteiro
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D058892:Adenosine Deaminase Inhibitors / Q000494:pharmacology; D000818:Animals; D000981:Antiprotozoal Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D001593:Benzyl Compounds / Q000494:pharmacology; D003839:Deoxyadenosines / Q000493:pharmacokinetics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D018512:Parasitemia / Q000188:drug therapy / Q000469:parasitology; D051381:Rats; D014345:Trypanosoma / Q000187:drug effects*; D014352:Trypanosomiasis / Q000097:blood / Q000188:drug therapy* / Q000469:parasitology
chemical_list: D058892:Adenosine Deaminase Inhibitors; D000981:Antiprotozoal Agents; D001593:Benzyl Compounds; D003839:Deoxyadenosines; C509055:erythro-(3-nonyl-p-aminobenzyl-adenine); C058120:cordycepin; D000225:Adenine