preADMET analysis and clinical aspects of dogs treated with the Organotellurium compound RF07: A possible control for canine visceral leishmaniasis?

•The action of RF-07 suggests that it has anti-inflammatory activity.•The action of RF-07 suggests that it reduces the burden of Leishmania.•The action of RF-07 suggests that its toxic activity is low. Tellurium compounds have been described as potential leishmanicides, bearing promising leishmanici...

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Veröffentlicht in:Environmental toxicology and pharmacology 2020-11, Vol.80, p.103470, Article 103470
Hauptverfasser: Viana Nunes, Adriana Maria, das Chagas Pereira de Andrade, Francisco, Filgueiras, Lívia Alves, de Carvalho Maia, Octávio Augusto, Cunha, Rodrigo L.O.R., Rodezno, Sindy V.A., Maia Filho, Antônio Luiz Martins, de Amorim Carvalho, Fernando Aécio, Braz, Debora Cavalcante, Mendes, Anderson Nogueira
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Sprache:eng
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Zusammenfassung:•The action of RF-07 suggests that it has anti-inflammatory activity.•The action of RF-07 suggests that it reduces the burden of Leishmania.•The action of RF-07 suggests that its toxic activity is low. Tellurium compounds have been described as potential leishmanicides, bearing promising leishmanicidal and antimalarial effects. Therefore, the present study investigated the pharmacological potential of the organotellurane compound RF07 through preADMET parameters, such as absorption, distribution, metabolism and excretion. After studying the pharmacokinetic properties of RF07, studies were carried out on dogs naturally infected with visceral leishmaniasis after the administration of RF07, in order to assess pathophysiological parameters. Thus, dogs were divided into 4 groups with administration of daily intraperitoneal injections for 3 weeks (containing RF07 or placebo). During the trial, hematological parameters, renal and hepatic toxicity were evaluated. Serum urea, creatinine, alkaline phosphatase, transaminases (GOT and GPT), as well as hemogram results, were evaluated before the first administration and during the second and third weeks after the start of the treatment. In dogs with VL, RF07 improved liver damage, regulated GPT levels and significantly decreased leukocyte count, promoting its regularization. These phenomena occurred at the end of the third week of treatment. The administration of RF07 promoted a significant decrease in the average levels of GOT and GPT after the third week of treatment and did not significantly alter the hematological parameters. The application of RF07 in the treatment of visceral leishmaniasis suggests that it is an alternative to the disease, since the reversal of clinical signs in dogs with VL requires the use of 0.6 mg/kg.
ISSN:1382-6689
1872-7077
DOI:10.1016/j.etap.2020.103470