Acute oral toxicity and assessment of blood pressure and kidney effects caused by oncocalyxone A

Paula Letícia Braga e Silva
OrcID
Laura Lícia Marcos da Costa
OrcID
Francisco Assis Nogueira Júnior
OrcID
Antônio Rafael Coelho Jorge
OrcID
Jeanine Morais Pereira
OrcID
Janaina Serra Azul Monteiro Evangelista
OrcID
Otília Deusdênia Loiola Pessoa
OrcID
Renata Sousa Alves
OrcID
Helena Serra Azul Monteiro
OrcID

    Paula Letícia Braga e Silva

    Federal University of Ceará, Department of Pharmacology and Physiology, Toxicology Laboratory, Rua Coronel Nunes de Melo, 1000, Rodolfo Teófilo, CEP 60416-000, Fortaleza, CE, Brazil.

    OrcID http://orcid.org/0000-0002-5899-8980

    Doutoranda do curso de Pós-graduação em Farmacologia da Universidade Federal do Ceará, Departamento de Farmacologia e Fisiologia. Desenvolve pesquisa na área de Farmacologia Renal no Laboratório de Farmacologia de Venenos, Toxinas e Lectinas (LAFAVET).

    Laura Lícia Marcos da Costa

    Federal University of Ceará, Department of Pharmacology and Physiology, Toxicology Laboratory, Rua Coronel Nunes de Melo, 1000, Rodolfo Teófilo, CEP 60416-000, Fortaleza, CE, Brazil.

    OrcID https://orcid.org/0000-0002-5994-1097

    Graduated in Pharmacy from the Federal University of Ceará (2013). Master in Pharmacology, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará (CAPES 6). Develops research in the area of renal and vascular pharmacology, diabetes and natural products at the Laboratory of Pharmacology of Poison, Toxins and Lectins (LAFAVET) , under the guidance of Profa. Dra. Helena Serra Azul Monteiro.

    Francisco Assis Nogueira Júnior

    Federal University of Ceará, Department of Pharmacology and Physiology, Toxicology Laboratory, Rua Coronel Nunes de Melo, 1000, Rodolfo Teófilo, CEP 60416-000, Fortaleza, CE, Brazil.

    OrcID https://orcid.org/0000-0001-9435-0244

    Graduated in Pharmacy from the State University of Paraíba (UEPB, 2014), Master in Pharmacology from the Federal University of Ceará (UFC, 2017), PhD student in Pharmacology also from UFC (in progress). Research developed in the field of renal pharmacology and snake venoms. Experience on duty at the Assistance and Toxicological Information Center in Campina Grande (Ceatox-CG), extension scholarship holder. Areas of Interest: Pharmacology, Toxicology, Toxinology and Toxicological Assistance.

    Antônio Rafael Coelho Jorge

    Federal University of Ceará, Department of Pharmacology and Physiology, Toxicology Laboratory, Rua Coronel Nunes de Melo, 1000, Rodolfo Teófilo, CEP 60416-000, Fortaleza, CE, Brazil.

    OrcID https://orcid.org/0000-0002-6756-2695

    Graduated in Biological Sciences at the Federal University of Ceará, he worked as an undergraduate in the area of protein biochemistry. Master and Doctor in Pharmacology from the Federal University of Ceará in the area of Renal Pharmacology and Toxinology, where he works in the field of renal hormones (ANP, Uroguaniline, Urodilatin) involved in the regulation of salt ingested in the diet and vascular and renal effects of venomous animal poisons . He worked as an undergraduate professor in the Nursing course at Faculdade INTA in Sobral-CE, where he taught the disciplines of Pharmacology, Microbiology and Immunology. Post-doctorate in Pharmacology (UFC) in the area of Toxins, poisons and biologically active peptides. Substitute Professor of Human Physiology at UFC in several undergraduate health courses.

    Jeanine Morais Pereira

    Federal University of Ceará, Department of Pharmacology and Physiology, Toxicology Laboratory, Rua Coronel Nunes de Melo, 1000, Rodolfo Teófilo, CEP 60416-000, Fortaleza, CE, Brazil.

    OrcID https://orcid.org/0000-0003-1340-8753

    Pharmacist graduated from the Federal University of Ceará in 2017. She was an initiation student at the Pharmacology Laboratory of poisons, toxins and lectins (LAFAVET). She was a Scientific Initiation student at the Infectious Diseases Laboratory (LDI), worked with a model of malnutrition and infection by E. coli. She was a monitor of the discipline of Production of medicines and cosmetics in the Pharmacy course, UFC. She has a course in injectables and vaccines. She worked in the pharmaceutical trade. She is currently a resident pharmacist in the UFC Multiprofessional Residency Program at the Maternidade Escola Assis Chateaubriand (MEAC) with an emphasis on Women's and Children's Health.

    Janaina Serra Azul Monteiro Evangelista

    Federal University of Ceará, Department of Pharmacology and Physiology, Toxicology Laboratory, Rua Coronel Nunes de Melo, 1000, Rodolfo Teófilo, CEP 60416-000, Fortaleza, CE, Brazil.

    OrcID https://orcid.org/0000-0002-9583-1573

    Graduated in Veterinary Medicine at the State University of Ceará (1992-1997); Master in Physiological Sciences (Level 4 - CAPES) from the State University of Ceará (1999-2000) and Doctorate in Pharmacology (Level 6 - CAPES) from the Federal University of Ceará (2004-2008). She is Adjunct Professor at the State University of Ceará (UECE), where she teaches the Discipline of Histology and General Veterinary Embryology. She held a Post Doc in Electron Microscopy at the Comparative Neurobiology Laboratory at the Cavanilles Institute for Biodiversity and Evolutionary Biology, Universidad de Valencia-Spain (2014-2015). She participates as an Effective Member of the Graduate Programs in Veterinary Sciences (level 6-CAPES) and of the Academic Master's Degree in Physiological Sciences at UECE (Level 4-CAPES), guiding Master and Doctoral students. She has experience in the area of ​​Morphology, with emphasis on Histology, highlighting the project: Morphological and Molecular Characterization of Mesenchymal Epithelial Transition and Myofibroblasts in Chronic Kidney Disease in Cats. Postdoctoral Orientation with the Project: Morphological study of the differences in the organs of different systems of small Cetaceos (dolphins) and Sirênios (manatees) of the Biodiversity of Northeast Brazil. Also having work in Toxicology with the following themes: Toxinology: toxins from animals, Crotalus durissus rattlesnake, Bothrops sp., Leptodactylus pentadactylus.

    Otília Deusdênia Loiola Pessoa

    Federal University of Ceará, Department of Pharmacology and Physiology, Toxicology Laboratory, Rua Coronel Nunes de Melo, 1000, Rodolfo Teófilo, CEP 60416-000, Fortaleza, CE, Brazil.

    OrcID https://orcid.org/0000-0002-1617-7586

    He graduated in Industrial Chemistry from the Federal University of Ceará, where he obtained the title of Doctor in Chemistry, with specialization in chemistry of natural products (1994). She was Vice-coordinator of the Graduate Program in Chemistry (09/99 - 09/01, 09/05 - 09/07, 09/13 - 09/13 - 01/14), Coordinator of the same Program (09/01 - 09/03), and president of the functional progression evaluation committee of the Science Center of the Federal University of Ceará (2012 - 2013). She is currently a Full Professor in the Department of Organic and Inorganic Chemistry, a researcher and productivity scholarship holder, level 1D of the National Council for Scientific Development. She guides projects of scientific initiation, master's, doctorate and post-gold in projects related to the determination of the chemical composition of plant extracts from the Northeastern flora, with ethnobotanical use or of pharmacological interest, mainly in the State of Ceará. She also works with the chemistry of natural marine products, including invertebrates, algae and associated microorganisms.

    Renata Sousa Alves

    Federal University of Ceará, Health Sciences Center, Department of Clinical and Toxicological Analysis. Rua Capitão Francisco Pedro 1210, Rodolfo Teófilo, CEP 60430-370, Fortaleza, CE, Brazil.

    OrcID https://orcid.org/0000-0003-0630-1499

    Graduated in Pharmacy - Qualification in Clinical Analysis from the Federal University of Ceará (2003), Master (2005) and Doctorate (2008) in Pharmacology from the Federal University of Ceará. He has experience in the Pharmacy area, with an emphasis on Clinical Analysis and Pharmacology, acting mainly on the following topics: Renal function, Endothelial dysfunction, Animal poisons and Toxins. She is currently Associate Professor II of the Department of Clinical and Toxicological Analysis at the Federal University of Ceará, coordinating the disciplines of Internship in Pharmacy III and Differentiated Internship in Clinical Analysis, Chee of the Laboratory of Clinical and Toxicological Analysis Prof Dr Eurico Litton Pinheiro de Freitas and Coordinator of the Professional Master's in Family Health - Northeast Network in Family Health (RENASF), a nucleader UFC in partnership with Fiocruz.

    Helena Serra Azul Monteiro

    Federal University of Ceará, Faculty of Medicine, Department of Physiology and Pharmacology Clinical Research Unit. Coronel Nunes de Melo, 1127, Porangabussu, CEP 60430-970, Fortaleza, CE, Brazil.

    OrcID https://orcid.org/0000-0002-8525-9657

    Graduated in Medicine from the Federal University of Ceará (1976) and doctorate in Medicine from UNICAMP (1990). Full Professor at the Department of Physiology and Pharmacology, Federal University of Ceará. She has experience in the field of Pharmacology, with an emphasis on Cardiovascular and Renal Pharmacology, working mainly on the following topics: toxinology, poisons, toxins, cardiovascular effects, renal effects. Leader of the research group LAFAVET (Laboratory of Pharmacology of Poison Toxins and Lectins) and CNPq researcher, level-1C with a research productivity grant, linked to the Department of Physiology and Pharmacology at UFC and the Graduate Program in Pharmacology and RENORBIO. She is an effective member of SBFTE, of the Brazilian Society of Toxinology (took part in the 2004-2006 board of directors) and a member of the International Society Toxinology (IST). Scientific exchange with national researchers from Instituto Butantan, UNESP, Federal University of Pernambuco, Catholic University of Goiás, State University of Ceará (UECE), University of Fortaleza (UNIFOR) and through sandwich doctoral co-supervision with University of Michigan (USA), with researcher Juan Calvette in Valencia, Spain and with Researcher Colin W. Taylor as PhD co-supervisor, at the University of Cambridge, Pharmacology, United Kingdom (2017). She was coordinator of the Graduate Program in Pharmacology at UFC (2007-2011) and representative of the Graduate Coordinators at UFC, at the University Council (2008-2009). She participated in the Management Committee of the BioMedicine Institute of the Brazilian Semi-Arid approved by CNPq. Head of Department of Physiology and Pharmacology (2015-2017 and 2017-2019) and member of the Departmental Council of the UFC Medical School (2015-2017 and 2017-2019).

Keywords

Oncocalyxone-A
Acute oral toxicity
Renal perfusion
Histological changes

Abstract

This study proposes to evaluate the toxicological, pressure and renal effects of onco-A in animal models in vivo and ex vivo. The Oncocalyxone-A (onco-A), isolated of Auxemma oncocalyx, was studied in doses of 1, 3 and 10 µg/mL. Female Swiss mice were used (20-25g) for the acute oral toxicity test. The data were compared by test t de Student, Two-Way ANOVA and post-test Bonferroni (p<0,05). The oral toxicity was considered low since it showed a DL50 ˃ 2000 mg/kg. Histological alterations on lung, renal and cardiac tissues were observed. About levels blood pressure of rats, the onco-A caused a significant reduction of mean arterial pressure, altered creatinine levels and, histological changes in cardiac and renal tissues. In isolated kidney perfusion onco-A caused an increase in perfusion pressure urinary flow and renal vascular resistance. The rate of glomerular filtration was reduced in concentrations 1 µg /mL and 10 µg/mL increasing the dose to 3 μg / mL. Photomicrographs of renal tissue after perfusion demonstrated significant histological changes induced by onco-A. It can be inferred that, although onco-A has presented low lethality in all experimental protocols performed, showed evidence of pulmonary, renal and cardiac toxicity.

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Author(s)

  • Paula Letícia Braga e Silva
    Federal University of Ceará, Department of Pharmacology and Physiology, Toxicology Laboratory, Rua Coronel Nunes de Melo, 1000, Rodolfo Teófilo, CEP 60416-000, Fortaleza, CE, Brazil.
    http://orcid.org/0000-0002-5899-8980
  • Laura Lícia Marcos da Costa
    Federal University of Ceará, Department of Pharmacology and Physiology, Toxicology Laboratory, Rua Coronel Nunes de Melo, 1000, Rodolfo Teófilo, CEP 60416-000, Fortaleza, CE, Brazil.
    https://orcid.org/0000-0002-5994-1097
  • Francisco Assis Nogueira Júnior
    Federal University of Ceará, Department of Pharmacology and Physiology, Toxicology Laboratory, Rua Coronel Nunes de Melo, 1000, Rodolfo Teófilo, CEP 60416-000, Fortaleza, CE, Brazil.
    https://orcid.org/0000-0001-9435-0244
  • Antônio Rafael Coelho Jorge
    Federal University of Ceará, Department of Pharmacology and Physiology, Toxicology Laboratory, Rua Coronel Nunes de Melo, 1000, Rodolfo Teófilo, CEP 60416-000, Fortaleza, CE, Brazil.
    https://orcid.org/0000-0002-6756-2695
  • Jeanine Morais Pereira
    Federal University of Ceará, Department of Pharmacology and Physiology, Toxicology Laboratory, Rua Coronel Nunes de Melo, 1000, Rodolfo Teófilo, CEP 60416-000, Fortaleza, CE, Brazil.
    https://orcid.org/0000-0003-1340-8753
  • Janaina Serra Azul Monteiro Evangelista
    Federal University of Ceará, Department of Pharmacology and Physiology, Toxicology Laboratory, Rua Coronel Nunes de Melo, 1000, Rodolfo Teófilo, CEP 60416-000, Fortaleza, CE, Brazil.
    https://orcid.org/0000-0002-9583-1573
  • Otília Deusdênia Loiola Pessoa
    Federal University of Ceará, Department of Pharmacology and Physiology, Toxicology Laboratory, Rua Coronel Nunes de Melo, 1000, Rodolfo Teófilo, CEP 60416-000, Fortaleza, CE, Brazil.
    https://orcid.org/0000-0002-1617-7586
  • Renata Sousa Alves
    Federal University of Ceará, Health Sciences Center, Department of Clinical and Toxicological Analysis. Rua Capitão Francisco Pedro 1210, Rodolfo Teófilo, CEP 60430-370, Fortaleza, CE, Brazil.
    https://orcid.org/0000-0003-0630-1499
  • Helena Serra Azul Monteiro
    Federal University of Ceará, Faculty of Medicine, Department of Physiology and Pharmacology Clinical Research Unit. Coronel Nunes de Melo, 1127, Porangabussu, CEP 60430-970, Fortaleza, CE, Brazil.
    https://orcid.org/0000-0002-8525-9657

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Acute oral toxicity and assessment of blood pressure and kidney effects caused by oncocalyxone A. Rev Fitos [Internet]. 2021 Mar. 31 [cited 2024 Nov. 21];15(1):93-107. Available from: https://revistafitos.far.fiocruz.br/index.php/revista-fitos/article/view/973
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