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

Environ Toxicol Pharmacol. 2020 Nov:80:103470. doi: 10.1016/j.etap.2020.103470. Epub 2020 Aug 16.

Abstract

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.

Keywords: Dogs; Hematological parameters; Hepatic toxicity; RF07; Renal toxicity; Visceral leishmaniasis.

MeSH terms

  • Alanine Transaminase / blood
  • Alkaline Phosphatase / blood
  • Animals
  • Antiprotozoal Agents* / pharmacokinetics
  • Antiprotozoal Agents* / pharmacology
  • Antiprotozoal Agents* / therapeutic use
  • Aspartate Aminotransferases / blood
  • Blood Cell Count
  • Body Weight / drug effects
  • Creatinine / blood
  • Dogs
  • Intestinal Absorption
  • Kidney / drug effects
  • Kidney / pathology
  • Leishmaniasis, Visceral* / blood
  • Leishmaniasis, Visceral* / drug therapy
  • Leishmaniasis, Visceral* / pathology
  • Leishmaniasis, Visceral* / veterinary
  • Liver / drug effects
  • Liver / pathology
  • Male
  • Models, Biological
  • Organometallic Compounds* / pharmacokinetics
  • Organometallic Compounds* / pharmacology
  • Organometallic Compounds* / therapeutic use
  • Spiro Compounds* / pharmacokinetics
  • Spiro Compounds* / pharmacology
  • Spiro Compounds* / therapeutic use
  • Tellurium* / pharmacokinetics
  • Tellurium* / pharmacology
  • Tellurium* / therapeutic use
  • Urea / blood

Substances

  • Antiprotozoal Agents
  • Organometallic Compounds
  • RF07 compound
  • Spiro Compounds
  • Urea
  • Creatinine
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Alkaline Phosphatase
  • Tellurium