Cordycepin (3′-deoxyadenosine) pentostatin (deoxycoformycin) combination treatment of mice experimentally infected withTrypanosoma evansi

Abstract

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.

Accounting for the Delay in the Transition from Acute to Chronic Pain: Axonal and Nuclear Mechanisms

“…The ethanol concentration of the final PGE 2 solution was ϳ2%, and the injection volume was 5 l. Stock solutions of cordycepin (1 g/l, dissolved in distilled water), prepared and further diluted in 0.9% NaCl, were used for intradermal injection into the dorsum of the hindpaw; for systemic treatment with cordycepin, a dose of 5 mg/kg, dissolved in distilled water, was administered intravenously in the tail vein. Because cordycepin is an adenosine analog that can be converted to an inactive metabolite by the enzyme adenosine deaminase (Tsai et al, 2010;Dalla Rosa et al, 2013), it must be administered with an adenosine deaminase inhibitor such as pentostatin (Johnston, 2011) to be effective (Koç and McCaffrey, 1995;Sugar and McCaffrey, 1998;Foss, 2000;Kodama et al, 2000;Yoshikawa et al, 2007). Pentostatin (1 mg/kg, dissolved in distilled water) was injected intravenously before cordycepin, in the same syringe, separated by an air bubble, to avoid mixing of the drugs.…”

Dose finding of 3′deoxyadenosine and deoxycoformycin for the treatment of Trypanosoma evansi infection: An effective and nontoxic dose

“…In a previous study we found that the combination of Cordycepin and Pentostatin was 100% effective in the treatment of T. evansi, however when both drugs were used alone they had no curative effect, but the alone Cordycepin alone is capable of delaying the parasitemia onset and prolong the life of mice [13]. However, the combination of these drugs in the doses used did lead to some liver and kidney damage [13]. As a result, the objective of this study was to reproduce the efficacy of a combination of Cordycepin and Pentostatin at different doses to mice infected by T. evansi, and thus determine whether an optimal dose could be found that was both nontoxic to the host and had the ability to clear T. evansi in experimentally infected mice.…”

“…In a previous study we found that the combination of Cordycepin and Pentostatin was 100% effective in the treatment of T. evansi, however when both drugs were used alone they had no curative effect, but the alone Cordycepin alone is capable of delaying the parasitemia onset and prolong the life of mice [13]. However, the combination of these drugs in the doses used did lead to some liver and kidney damage [13].…”

“…In particular, their dependence on the nucleoside salvage pathway from the body fluids of their hosts [11] has been exploited as a therapeutic target [12]. Our recent studies suggest that a combination of 3 0 deoxyadenosine (Cordycepin) and deoxycoformycin (Pentostatin) in mice experimentally infected with T. evansi is curative [13], and has a beneficial role in treating hematological parameters and the activity of ectoadenosine deaminase (E-ADA) in the host [14]. Mechanistically, as an adenosine analogue, Cordycepin most likely replaces the ribose of adenosine and consequently interrupts nucleolar RNA synthesis [15e17].…”

“…As a result, the objective of this study was to reproduce the efficacy of a combination of Cordycepin and Pentostatin at different doses to mice infected by T. evansi, and thus determine whether an optimal dose could be found that was both nontoxic to the host and had the ability to clear T. evansi in experimentally infected mice. In this study we did not test the two drugs separately because we have previously shown that they were not curative when used alone [13].…”