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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container_title Environmental toxicology and pharmacology
container_volume 80
creator 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
description •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.
doi_str_mv 10.1016/j.etap.2020.103470
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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.</description><identifier>ISSN: 1382-6689</identifier><identifier>EISSN: 1872-7077</identifier><identifier>DOI: 10.1016/j.etap.2020.103470</identifier><identifier>PMID: 32814174</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Alanine Transaminase - blood ; Alkaline phosphatase ; Alkaline Phosphatase - blood ; Animals ; Antiprotozoal Agents - pharmacokinetics ; Antiprotozoal Agents - pharmacology ; Antiprotozoal Agents - therapeutic use ; Aspartate Aminotransferases - blood ; Blood Cell Count ; Body Weight - drug effects ; Clinical aspects ; Creatinine ; Creatinine - blood ; Dogs ; Evaluation ; Health services ; Hematological parameters ; Hematology ; Hepatic toxicity ; Intestinal Absorption ; Kidney - drug effects ; Kidney - pathology ; Leishmaniasis, Visceral - blood ; Leishmaniasis, Visceral - drug therapy ; Leishmaniasis, Visceral - pathology ; Leishmaniasis, Visceral - veterinary ; Leukocytes ; Liver - drug effects ; Liver - pathology ; Male ; Metabolism ; Models, Biological ; Organometallic Compounds - pharmacokinetics ; Organometallic Compounds - pharmacology ; Organometallic Compounds - therapeutic use ; Parameters ; Parasitic diseases ; Pharmacokinetics ; Pharmacology ; Placebos ; Regularization ; Renal toxicity ; RF07 ; Spiro Compounds - pharmacokinetics ; Spiro Compounds - pharmacology ; Spiro Compounds - therapeutic use ; Tellurium ; Tellurium - pharmacokinetics ; Tellurium - pharmacology ; Tellurium - therapeutic use ; Tellurium compounds ; Toxicity ; Urea ; Urea - blood ; Vector-borne diseases ; Visceral leishmaniasis</subject><ispartof>Environmental toxicology and pharmacology, 2020-11, Vol.80, p.103470, Article 103470</ispartof><rights>2020 Elsevier B.V.</rights><rights>Copyright © 2020 Elsevier B.V. All rights reserved.</rights><rights>Copyright Elsevier Science Ltd. 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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.</description><subject>Alanine Transaminase - blood</subject><subject>Alkaline phosphatase</subject><subject>Alkaline Phosphatase - blood</subject><subject>Animals</subject><subject>Antiprotozoal Agents - pharmacokinetics</subject><subject>Antiprotozoal Agents - pharmacology</subject><subject>Antiprotozoal Agents - therapeutic use</subject><subject>Aspartate Aminotransferases - blood</subject><subject>Blood Cell Count</subject><subject>Body Weight - drug effects</subject><subject>Clinical aspects</subject><subject>Creatinine</subject><subject>Creatinine - blood</subject><subject>Dogs</subject><subject>Evaluation</subject><subject>Health services</subject><subject>Hematological parameters</subject><subject>Hematology</subject><subject>Hepatic toxicity</subject><subject>Intestinal Absorption</subject><subject>Kidney - drug effects</subject><subject>Kidney - pathology</subject><subject>Leishmaniasis, Visceral - blood</subject><subject>Leishmaniasis, Visceral - drug therapy</subject><subject>Leishmaniasis, Visceral - pathology</subject><subject>Leishmaniasis, Visceral - veterinary</subject><subject>Leukocytes</subject><subject>Liver - drug effects</subject><subject>Liver - pathology</subject><subject>Male</subject><subject>Metabolism</subject><subject>Models, Biological</subject><subject>Organometallic Compounds - pharmacokinetics</subject><subject>Organometallic Compounds - pharmacology</subject><subject>Organometallic Compounds - therapeutic use</subject><subject>Parameters</subject><subject>Parasitic diseases</subject><subject>Pharmacokinetics</subject><subject>Pharmacology</subject><subject>Placebos</subject><subject>Regularization</subject><subject>Renal toxicity</subject><subject>RF07</subject><subject>Spiro Compounds - pharmacokinetics</subject><subject>Spiro Compounds - pharmacology</subject><subject>Spiro Compounds - therapeutic use</subject><subject>Tellurium</subject><subject>Tellurium - pharmacokinetics</subject><subject>Tellurium - pharmacology</subject><subject>Tellurium - therapeutic use</subject><subject>Tellurium compounds</subject><subject>Toxicity</subject><subject>Urea</subject><subject>Urea - blood</subject><subject>Vector-borne diseases</subject><subject>Visceral leishmaniasis</subject><issn>1382-6689</issn><issn>1872-7077</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9UV1rFTEQDWKxtfUP-CABn_eaz81eEeRSWyu0FEp9DtlktjeX7GZNsi39H_5gc7nVR59mmDlzZuYchN5TsqKEtp92KyhmXjHC9gUuFHmFTminWKOIUq9rzjvWtG23PkZvc94RQiXn3Rt0zFlHBVXiBP2eE2y-3VzcYzOZ8Jx9ronDNvjJWxOwyTPYknEcsIsPGZcEpoDDT75scdkCvk0PZooFQliSX0Zs4zjHpVLcXRL1GW_wHHP2fYDamUqKAQ8xYWsmPwF-9NlCqmsC-Lwda9HUC76eoaPBhAzvXuIp-nl5cX9-1Vzffv9xvrluLO9EaVxvBOkFrGlvlZO8Z1Yy6TihhLWGKQaEOCGBM7oeOmd5q7hUQgnRgwVJ-Cn6eOCdU_y1QC56F5dUdciaSSIFXUtKK4odUDbVVxIMek5-NOlZU6L3Ruid3huh90bogxF16MML9dKP4P6N_FW-Ar4cAFAffPSQdLYeJgvOp6q4dtH_j_8PiBeanA</recordid><startdate>202011</startdate><enddate>202011</enddate><creator>Viana Nunes, Adriana Maria</creator><creator>das Chagas Pereira de Andrade, Francisco</creator><creator>Filgueiras, Lívia Alves</creator><creator>de Carvalho Maia, Octávio Augusto</creator><creator>Cunha, Rodrigo L.O.R.</creator><creator>Rodezno, Sindy V.A.</creator><creator>Maia Filho, Antônio Luiz Martins</creator><creator>de Amorim Carvalho, Fernando Aécio</creator><creator>Braz, Debora Cavalcante</creator><creator>Mendes, Anderson Nogueira</creator><general>Elsevier B.V</general><general>Elsevier Science Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7ST</scope><scope>7TK</scope><scope>7U7</scope><scope>C1K</scope><scope>SOI</scope><orcidid>https://orcid.org/0000-0003-1123-6548</orcidid><orcidid>https://orcid.org/0000-0002-9778-3667</orcidid></search><sort><creationdate>202011</creationdate><title>preADMET analysis and clinical aspects of dogs treated with the Organotellurium compound RF07: A possible control for canine visceral leishmaniasis?</title><author>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</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c384t-dba40b4e91bc7d53b2c525d301026a272e00d45e3219f8dc3673574744bece503</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Alanine Transaminase - blood</topic><topic>Alkaline phosphatase</topic><topic>Alkaline Phosphatase - blood</topic><topic>Animals</topic><topic>Antiprotozoal Agents - pharmacokinetics</topic><topic>Antiprotozoal Agents - pharmacology</topic><topic>Antiprotozoal Agents - therapeutic use</topic><topic>Aspartate Aminotransferases - blood</topic><topic>Blood Cell Count</topic><topic>Body Weight - drug effects</topic><topic>Clinical aspects</topic><topic>Creatinine</topic><topic>Creatinine - blood</topic><topic>Dogs</topic><topic>Evaluation</topic><topic>Health services</topic><topic>Hematological parameters</topic><topic>Hematology</topic><topic>Hepatic toxicity</topic><topic>Intestinal Absorption</topic><topic>Kidney - drug effects</topic><topic>Kidney - pathology</topic><topic>Leishmaniasis, Visceral - blood</topic><topic>Leishmaniasis, Visceral - drug therapy</topic><topic>Leishmaniasis, Visceral - pathology</topic><topic>Leishmaniasis, Visceral - veterinary</topic><topic>Leukocytes</topic><topic>Liver - drug effects</topic><topic>Liver - pathology</topic><topic>Male</topic><topic>Metabolism</topic><topic>Models, Biological</topic><topic>Organometallic Compounds - pharmacokinetics</topic><topic>Organometallic Compounds - pharmacology</topic><topic>Organometallic Compounds - therapeutic use</topic><topic>Parameters</topic><topic>Parasitic diseases</topic><topic>Pharmacokinetics</topic><topic>Pharmacology</topic><topic>Placebos</topic><topic>Regularization</topic><topic>Renal toxicity</topic><topic>RF07</topic><topic>Spiro Compounds - pharmacokinetics</topic><topic>Spiro Compounds - pharmacology</topic><topic>Spiro Compounds - therapeutic use</topic><topic>Tellurium</topic><topic>Tellurium - pharmacokinetics</topic><topic>Tellurium - pharmacology</topic><topic>Tellurium - therapeutic use</topic><topic>Tellurium compounds</topic><topic>Toxicity</topic><topic>Urea</topic><topic>Urea - blood</topic><topic>Vector-borne diseases</topic><topic>Visceral leishmaniasis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Viana Nunes, Adriana Maria</creatorcontrib><creatorcontrib>das Chagas Pereira de Andrade, Francisco</creatorcontrib><creatorcontrib>Filgueiras, Lívia Alves</creatorcontrib><creatorcontrib>de Carvalho Maia, Octávio Augusto</creatorcontrib><creatorcontrib>Cunha, Rodrigo L.O.R.</creatorcontrib><creatorcontrib>Rodezno, Sindy V.A.</creatorcontrib><creatorcontrib>Maia Filho, Antônio Luiz Martins</creatorcontrib><creatorcontrib>de Amorim Carvalho, Fernando Aécio</creatorcontrib><creatorcontrib>Braz, Debora Cavalcante</creatorcontrib><creatorcontrib>Mendes, Anderson Nogueira</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium &amp; 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ispartof Environmental toxicology and pharmacology, 2020-11, Vol.80, p.103470, Article 103470
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source MEDLINE; ScienceDirect Journals (5 years ago - present)
subjects Alanine Transaminase - blood
Alkaline phosphatase
Alkaline Phosphatase - blood
Animals
Antiprotozoal Agents - pharmacokinetics
Antiprotozoal Agents - pharmacology
Antiprotozoal Agents - therapeutic use
Aspartate Aminotransferases - blood
Blood Cell Count
Body Weight - drug effects
Clinical aspects
Creatinine
Creatinine - blood
Dogs
Evaluation
Health services
Hematological parameters
Hematology
Hepatic toxicity
Intestinal Absorption
Kidney - drug effects
Kidney - pathology
Leishmaniasis, Visceral - blood
Leishmaniasis, Visceral - drug therapy
Leishmaniasis, Visceral - pathology
Leishmaniasis, Visceral - veterinary
Leukocytes
Liver - drug effects
Liver - pathology
Male
Metabolism
Models, Biological
Organometallic Compounds - pharmacokinetics
Organometallic Compounds - pharmacology
Organometallic Compounds - therapeutic use
Parameters
Parasitic diseases
Pharmacokinetics
Pharmacology
Placebos
Regularization
Renal toxicity
RF07
Spiro Compounds - pharmacokinetics
Spiro Compounds - pharmacology
Spiro Compounds - therapeutic use
Tellurium
Tellurium - pharmacokinetics
Tellurium - pharmacology
Tellurium - therapeutic use
Tellurium compounds
Toxicity
Urea
Urea - blood
Vector-borne diseases
Visceral leishmaniasis
title preADMET analysis and clinical aspects of dogs treated with the Organotellurium compound RF07: A possible control for canine visceral leishmaniasis?
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