The lack of alternatives for treatment of Chagas' disease is a major problem in Latin America where the disease is still present. Primarily diagnosed patients are generally treated with benznidazole and nifurtimox (now discontinued). However, in many countries like Mexico, both drugs are not available. Allopurinol has been reported as an agent with activity against blood trypomastigotes and amastigotes of
Trypanosoma cruzi (
Berens et al., 1982) but there are conflicting views about its effectiveness, as well as other pharmaceutical options used to treat the disease.
Carignani et al., (2000) describes that under experimental conditions, allopurinol is not able to eliminate the presence of
Trypanosoma cruzi in from infected triatomines. In contrast,
Coura (2009) found that the use of allopurinol in infected patients may be an alternative choice (like the beznidazol) when is administered (8 mg/Kg/day) for at least for 60 days and preferably in combination with another drug with antiprotozoal activity towards
Trypanosoma cruzi (as benznidazole and ketoconazole). Also
Apt (1998) described that only 44% of patients treated with this same dose elimination of the parasite was observed. These results differ from the observed in this study because no complete elimination of parasitemia in infected animals treated with allopurinol was observed. In contrast, during the first 5 days after beginning of treatment (day 20 bioassay) the parasitemia was higher even than in the negative control animals, and antiprotozoal activity was observed until day 24 and 28 post infection. However, it should be noted that the duration of this trial was only 28 days and we can not compare the activity at 60 days as described by the authors mentioned. Similarly,
Gobbi et al., (2007) mentioned that treatment with allopurinol 15 mg / kg in infected mice showed obvious reduction of parasitemia and absence of electrocardiographic changes. Probably because a lower dose of this drug was used in this study, there was not an entirely appropriate response towards it.
On the other hand, there are few
in vivo studies evaluating the antiprotozoal activity of molecules obtained from natural products. The activity of (8-hydroxymethylen)-trieicosanyl acetate observed is similar to other studies where a reduction of the parasitemia has been observed when treatments with plant crude extracts were used, like
Aderbauer et al., (2008) who studied the root extract of
Securidaca longepedunculata and the leaf extract of
Guiera senegalensis demonstrating than were able to reduce parasitaemia in mice, experimentally infected with
Trypanosoma brucei brucei at the dose of 150 mg/kg b.w. intraperitoneally, two times daily for 3 days but only by 48 and 42% respectively for each extract. Also,
Caceres et al., (1998) reported than crude extracts from
Neurolaena lobata, Solanum americanum Acalypha guatemalensis, Petiveria alliacea and
Tridax procumbens have an
in vitro and
in vivo activity against
T. cruzi, but the administration to mice orally of
S. americanum showed intraperitoneal subacute toxicity
. In the present study the advantage of the evaluated compound is that no toxicity is observed for
in vitro and
in vivo studies (
Guzman et al., 2004;
Jimenez-Coello et al., 2010).
Results about antiprotozoal activity of (8-hydroxymethylen)-trieicosanyl acetate under in
in vivo conditions is also similar with the reported by
Sülsen et al., (2008); they identify and isolated a pair of compounds from the medicinal plant
Ambrosia tenuifolia Sprengel (Asteraceae), but in these experiment infection in mice included 5 × 10
3 trypomastigotes, in contrast with this bioassay the inoculation to infect mice included 50 × 10
6 parasites with a highly pathogenic strain of
Trypanosoma cruzi (H4), demonstring a clear antriprotozoal activity of the evaluated compound.
Cunha et al., 2006, reported a triterpene isolated from
Miconia species showing a good antiprotozoal activity
in vivo against
T. cruzi. However, the activity of those compound over the intracellurar stage of the parasite was not reported in contrast with the activity observed with (8-hydroxymethylen)-trieicosanyl acetate over the amastigote nests. Another
in vivo study has been conducted to evaluate indirect derivates from plants as crude extract of brazilian green propolis, but there were used as immunostimulant, searching a better immunological response against the infection towards the parasite. However, as observed in many drugs including the (8-hydroxymethylen)-trieicosanyl acetate, the crude extract was not able to eliminate completely the parasites from bloodstream (
Dantas et al., 2006).
For (8-hydroxymethylen)-trieicosanyl acetate, the best results were observed when treatment started simultaneously with the infection (
Jimenez-Coello et al., 2010), and the evaluated compound showed a high antiprotozoal activity than other crude extract such as
Zanthoxylum naranjillo (
Bastos et al., 1999), even the amount of parasites for inoculation used in the present study was 10 times higher than in that study, with the mentioned virulent strain of
T. cruzi (H4 strain). In the present study, when the compound was administrated 15 days after infection, an inhibition of the replication of the parasite was observed even when the infection was already well established. Results showed a reduction in parasitemia and a significant reduction in the number of amastigote nests in heart tissue (p<0.05), these results are difficult to compare with other studies because not many reports from crude extracts or medicinal isolated compounds includes the evaluation of developmental forms of the parasite. However, it is important to mention that the evaluated compound appears to have an effect over the replicative intracellular stage of
T. cruzi.On the other hand, results observed in mice infected and treated simultaneously (in the second bioassay), during the first 20 days of treatment, the parasitemia in treated mice with the compound was similar to those previously reported (
Jimenez-Coello et al., 2010) however, it was observed that parasitemia level is increased when the administration of the compound was suppressed, demonstrating that in the treated animals with the compound a reduction in the number of amastigote nests in comparison with control groups may occurs.
It is necessary to evaluate the effectiveness of (8-hydroxymethylen)-trieicosanyl acetate during longer periods of time, during the chronic phase of the disease and maybe in combination with other antitrypanosomal drugs.
AC Karla Yolanda Acosta-Viana,A Maria Salud Pérez G,
