Susceptibility of Trypanosoma evansi to cordycepin
Department of microbiology and parasitology, universidade Federal de Santa Maria, Santa Maria, Brazil.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Impact Factor: 2.02). 05/2011; 65(3):220-3. DOI: 10.1016/j.biopha.2011.02.007
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.
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ABSTRACT: The potent activity against Trypanosomes and health beneficial effects of curcumin (Cur) has been demonstrated in various experimental models. In this study, we evaluated the in vivo effect of Cur as trypanocide and as potential anti-inflammatory agent, through the evaluation of immunomodulatory mechanisms in rats infected with Trypanosoma evansi. Daily oral Cur was administered at doses of 0, 20 or 60 mg/kg as preventive treatment (30 and 15 days pre infection) and as treatment (post infection). The treatment of the groups continued until the day of euthanasia. Fifteen days after inoculation, parasitemia, plasma proinflammatory cytokines (IFN-γ, TNF-α, IL-1, IL-6), anti-inflammatory cytokines (IL-10) and blood acetylcholinesterase activity (AChE) were analyzed. Pretreatment with Cur reduced parasitemia and lethality. Cur inhibited AChE activity and improved immunological response by cytokines proinflammatory, fundamental during T. evansi infection. We found that Cur is not so important as an antitrypanosomal activity but as immunomodulator agent. These findings reveal that the preventive use of Cur stimulates anti-inflammatory mechanisms, reducing an excessive inflammatory response.Parasitology International 11/2012; 62(2). DOI:10.1016/j.parint.2012.11.004 · 1.86 Impact Factor
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ABSTRACT: SUMMARY The aim of this study was to evaluate the anti-trypanosomal effect of treatment with 3'-deoxyadenosine (cordycepin) combined with deoxycoformycin (pentostatin: inhibitor of the enzyme adenosine deaminase) in vitro by using mice experimentally infected with Trypanosoma evansi. In vitro, a dose-dependent trypanocidal effect of cordycepin was observed against the parasite. In the in vivo trials, the two drugs were used individually and in combination of different doses. The drugs when used individually had no curative effect on infected mice. However, the combination of cordycepin (2 mg kg-1) and pentostatin (2 mg kg-1) was 100% effective in the T. evansi-infected groups. There was an increase in levels of some biochemical parameters, especially on liver enzymes, which were accompanied by histological lesions in the liver and kidneys. Based on these results we conclude that treatment using the combination of 3'-deoxyadenosine with deoxycoformycin has a curative effect on mice infected with T. evansi. However, the therapeutic protocol tested led to liver and kidney damage, manifested by hepatotoxicity and nephrotoxicity.Parasitology 01/2013; 140(5):1-9. DOI:10.1017/S0031182012001990 · 2.56 Impact Factor
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ABSTRACT: This study aimed to verify the effect of 3'-deoxyadenosine and deoxycoformycin on hematologic parameters and adenosine deaminase (ADA) activity in plasma and brain of mice infected with Trypanosoma evansi. Seventy animals were divided into seven groups, which were divided into two subgroups each for sampling on days 4 and 8 post-infection (PI). The groups were composed of three uninfected groups (A - C), namely, not-treated (A), treated with 3'-deoxyadenosine (B), and treated with deoxycoformycin (C) and four infected groups, mice with T. evansi (D - G), namely, not-treated (D), treated with 3'-deoxyadenosine (E), treated with deoxycoformycin (F), and treated with a combination 3'-deoxyadenosine and deoxycoformycin (G). Hematological parameters and ADA activity were evaluated in plasma and brain. Animals in groups B and C exhibited a reduction in the levels of plasma total protein compared group A. Animals in groups D and F showed changes in the hematological parameters. The ADA activity significantly reduced in the animals of groups C, D, F and G. Mice in the group E presented increased ADA activity in plasma. Therefore, we conclude that the treatment interferes significantly in the hematologic parameters in mice infected with T. evansi. On the other hand, when the ADA inhibitor was used we observed a significant decrease in the values of hematocrit, total erythrocytes, and hemoglobin concentration. The deoxycoformycin was able to inhibit the ADA activity of parasite thus it may be one of the mechanisms of efficacy of this treatment.Experimental Parasitology 08/2013; 135(2). DOI:10.1016/j.exppara.2013.07.019 · 1.64 Impact Factor
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