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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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 |
format | Article |
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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. Nov 2020</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c384t-dba40b4e91bc7d53b2c525d301026a272e00d45e3219f8dc3673574744bece503</citedby><cites>FETCH-LOGICAL-c384t-dba40b4e91bc7d53b2c525d301026a272e00d45e3219f8dc3673574744bece503</cites><orcidid>0000-0003-1123-6548 ; 0000-0002-9778-3667</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1382668920301460$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32814174$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><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><title>preADMET analysis and clinical aspects of dogs treated with the Organotellurium compound RF07: A possible control for canine visceral leishmaniasis?</title><title>Environmental toxicology and pharmacology</title><addtitle>Environ Toxicol Pharmacol</addtitle><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.</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 & Calcified Tissue Abstracts</collection><collection>Environment Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Environment Abstracts</collection><jtitle>Environmental toxicology and pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Viana Nunes, Adriana Maria</au><au>das Chagas Pereira de Andrade, Francisco</au><au>Filgueiras, Lívia Alves</au><au>de Carvalho Maia, Octávio Augusto</au><au>Cunha, Rodrigo L.O.R.</au><au>Rodezno, Sindy V.A.</au><au>Maia Filho, Antônio Luiz Martins</au><au>de Amorim Carvalho, Fernando Aécio</au><au>Braz, Debora Cavalcante</au><au>Mendes, Anderson Nogueira</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>preADMET analysis and clinical aspects of dogs treated with the Organotellurium compound RF07: A possible control for canine visceral leishmaniasis?</atitle><jtitle>Environmental toxicology and pharmacology</jtitle><addtitle>Environ Toxicol Pharmacol</addtitle><date>2020-11</date><risdate>2020</risdate><volume>80</volume><spage>103470</spage><pages>103470-</pages><artnum>103470</artnum><issn>1382-6689</issn><eissn>1872-7077</eissn><abstract>•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.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>32814174</pmid><doi>10.1016/j.etap.2020.103470</doi><orcidid>https://orcid.org/0000-0003-1123-6548</orcidid><orcidid>https://orcid.org/0000-0002-9778-3667</orcidid></addata></record> |
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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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