Hydroethanolic extract from Endopleura uchi (Huber) Cuatrecasas and its marker bergenin: Toxicological and pharmacokinetic studies in silico and in vivo on zebrafish
| Autor: | Helison de Oliveira Carvalho, Brenda Lorena Sánchez-Ortiz, Karyny Roberta Tavares Picanço, Luciane B. Silva, Rodrigo Cardoso Ataíde, Raphaelle Sousa Borges, Andrés Navarrete, José Carlos Tavares Carvalho, Cleydson B. R. Santos, Gloria Melisa Gonzalez Anduaga, Larissa Daniele Machado Góes, Beatriz Martins de S a Hyacienth, Arlindo César Matias Pereira |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
HBA
Hydrogen bonding acceptors EEu Endopleura uchi stem bark hydroethanolic extract IAN Regional Herbarium of the Eastern Amazonian Embrapa PPB Plasma protein binding Health Toxicology and Mutagenesis In silico 010501 environmental sciences Pharmacology Toxicology 01 natural sciences 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Pharmacokinetics In vivo lcsh:RA1190-1270 Biotrasformation Bergenin BBB Brain-blood partition coefficient (C.brain/C.blood) 0105 earth and related environmental sciences ComputingMethodologies_COMPUTERGRAPHICS lcsh:Toxicology. Poisons Hepatoxity CYP3A4 Chemistry ALT Alanine aminotransferase hERG ether-a-go-related human gene Regular Article MM Molecular mass Acute toxicity HIA Human intestinal absorption HAI Index of Histopathological Changes Phytochemical Toxicity HBD Hydrogen bonding donors Endopleura uchi P-Gp P-glycoprotein Nephrotoxity AST Aspartate aminotransferase 030217 neurology & neurosurgery |
| Zdroj: | Toxicology Reports, Vol 7, Iss, Pp 217-232 (2020) Toxicology Reports |
| ISSN: | 2214-7500 |
| Popis: | Graphical abstract Highlights • E. uchi stem bark hydroethanolic extract in zebrafish. • Evaluating the in silico pharmacokinetic and toxicological parameters. • Behavioral, biochemical and histopathological changes was dose dependent. • In silico bergenin and its metabolites showed high intestinal absorption. • Bergenin inhibited CYP2C9, CYP3A4 and CYP2C19. Endopleura uchi, is used for the treatment of inflammatory disease and related to the female reproductive tract. The aim of this study was to evaluate the acute toxicity of the Endopleura uchi stem bark hydroethanolic extract (EEu) in zebrafish, emphasizing the histopathological and biochemical parameters, as well as evaluating the in silico pharmacokinetic and toxicological parameters of the phytochemical/pharmacological marker, bergenin, as their metabolites. The animals were orally treated with EEu at a single dose of 75 mg/kg, 500 mg/kg, 1000 mg/kg and 3000 mg/kg. the oral LD50 of the EEu higher to the dose of 3000 mg/kg. Behavioral, biochemical and histopathological changes were dose dependent. In silico pharmacokinetic predictions for bergenin and its metabolites showed moderate absorption in high human intestinal absorption (HIA) and Caco-2 models, reduced plasma protein binding, by low brain tissue binding and no P-glycoprotein (P-Gp) inhibition. Their metabolism is defined by the CYP450 enzyme, in addition to bergenin inhibition of CYP2C9, CYP3A4 and CYP2C19. In the bergenin and its metabolites in silico toxicity test it have been shown to cause carcinogenicity and a greater involvement of the bergenin with the CYP enzymes in the I and II hepatic and renal metabolism’s phases was observed. It is possible to suggest that the histopathological damages are involved with the interaction of this major compound and its metabolites at the level of the cellular-biochemical mechanisms which involve the absorption, metabolization and excretion of these possible prodrug and drug. |
| Databáze: | OpenAIRE |
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