Toxicokinetics of arenobufagin and its cardiotoxicity mechanism exploration based on lipidomics and proteomics approaches in rats
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus Norvegicus
SUBMITTER: 
Haiyu Zhao
PROVIDER: PXD028622 | iProX | Fri Sep 17 00:00:00 BST 2021
REPOSITORIES: iProX
Publications
Toxicokinetics of Arenobufagin and its Cardiotoxicity Mechanism Exploration Based on Lipidomics and Proteomics Approaches in Rats.
Zhao Lijuan L Han Lingyu L Wei Xiaolu X Zhou Yanyan Y Zhang Yanqiong Y Si Nan N Wang Hongjie H Yang Jian J Bian Baolin B Zhao Haiyu H
Frontiers in pharmacology 20211222
Arenobufagin (ArBu), one of the main active bufadienolides of toad venom with cardiotonic effect, analgesic effect, and outstanding anti-tumor potentiality, is also a potential cardiotoxic component. In the present study, the cardiac effect of ArBu and its underlying mechanism were explored by integrating data such as heart rates, toxicokinetics, myocardial enzyme and brain natriuretic peptide (BNP) activity, pathological sections, lipidomics and proteomics. Under different doses, the cardiac ef ...[more]
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This model is described in the article:
A pharmacokinetic model to predict the PK interaction of L-dopa and benserazide in rats.
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Abstract:
PURPOSE:
To study the PK interaction of L-dopa/benserazide in rats. METHODS: Male rats received a single oral dose of 80 mg/kg L-dopa or 20 mg/kg benserazide or 80/20 mg/kg L-dopa/benserazide. Based on plasma concentrations the kinetics of L-dopa, 3-O-methyldopa (3-OMD), benserazide, and its metabolite Ro 04-5127 were characterized by noncompartmental analysis and a compartmental model where total L-dopa clearance was the sum of the clearances mediated by amino-acid-decarboxylase (AADC), catechol-O-methyltransferase and other enzymes. In the model Ro 04-5127 inhibited competitively the L-dopa clearance by AADC.
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The coadministration of L-dopa/benserazide resulted in a major increase in systemic exposure to L-dopa and 3-OMD and a decrease in L-dopa clearance. The compartmental model allowed an adequate description of the observed L-dopa and 3-OMD concentrations in the absence and presence of benserazide. It had an advantage over noncompartmental analysis because it could describe the temporal change of inhibition and recovery of AADC.
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The above issue is caused by some initial assignments which are not calculated when COPASI imports the file. This issue should not be present in newer releases of COPASI.
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and identified by: MODEL0910130001
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