دورية أكاديمية
Early preclinical screening using zebrafish ( Danio rerio ) reveals the safety of the candidate anti-inflammatory therapeutic agent Tn P.
العنوان: | Early preclinical screening using zebrafish ( Danio rerio ) reveals the safety of the candidate anti-inflammatory therapeutic agent Tn P. |
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المؤلفون: | Batista-Filho J; Immunoregulation Unit of the Laboratory of Applied Toxinology (CeTICs/FAPESP), Butantan Institute, Vital Brazil Avenue, 1500, Butantan, 05503-009, São Paulo, Brazil.; Post-Graduation Program of Toxinology, Butantan Institute, São Paulo, SP, Brazil., Falcão MAP; Immunoregulation Unit of the Laboratory of Applied Toxinology (CeTICs/FAPESP), Butantan Institute, Vital Brazil Avenue, 1500, Butantan, 05503-009, São Paulo, Brazil., Maleski ALA; Immunoregulation Unit of the Laboratory of Applied Toxinology (CeTICs/FAPESP), Butantan Institute, Vital Brazil Avenue, 1500, Butantan, 05503-009, São Paulo, Brazil.; Post-Graduation Program of Toxinology, Butantan Institute, São Paulo, SP, Brazil., Soares ABS; Immunoregulation Unit of the Laboratory of Applied Toxinology (CeTICs/FAPESP), Butantan Institute, Vital Brazil Avenue, 1500, Butantan, 05503-009, São Paulo, Brazil., Balan-Lima L; Immunoregulation Unit of the Laboratory of Applied Toxinology (CeTICs/FAPESP), Butantan Institute, Vital Brazil Avenue, 1500, Butantan, 05503-009, São Paulo, Brazil., Disner GR; Immunoregulation Unit of the Laboratory of Applied Toxinology (CeTICs/FAPESP), Butantan Institute, Vital Brazil Avenue, 1500, Butantan, 05503-009, São Paulo, Brazil., Lima C; Immunoregulation Unit of the Laboratory of Applied Toxinology (CeTICs/FAPESP), Butantan Institute, Vital Brazil Avenue, 1500, Butantan, 05503-009, São Paulo, Brazil., Lopes-Ferreira M; Immunoregulation Unit of the Laboratory of Applied Toxinology (CeTICs/FAPESP), Butantan Institute, Vital Brazil Avenue, 1500, Butantan, 05503-009, São Paulo, Brazil. |
المصدر: | Toxicology reports [Toxicol Rep] 2020 Dec 10; Vol. 8, pp. 13-22. Date of Electronic Publication: 2020 Dec 10 (Print Publication: 2021). |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: Elsevier Ireland Ltd Country of Publication: Ireland NLM ID: 101630272 Publication Model: eCollection Cited Medium: Internet ISSN: 2214-7500 (Electronic) Linking ISSN: 22147500 NLM ISO Abbreviation: Toxicol Rep Subsets: PubMed not MEDLINE |
أسماء مطبوعة: | Original Publication: [Ireland] : Elsevier Ireland Ltd., [2014]- |
مستخلص: | The patented anti-inflammatory peptide Tn P had its effectiveness recently confirmed in vivo in a murine model of multiple sclerosis and asthma. In this work, the safety of the Tn P was evaluated in investigative toxicology tests using zebrafish ( Danio rerio ) as a model. We conducted the OECD #236 test to investigate effects of the Tn P on the survival, hatching performance, and morphological formation of zebrafish embryos. After determining these endpoints, morphometric analysis termination of locomotion eartbeat rate in zebrafish larvae were evaluated to identify adverse effects such as neurotoxicity and cardiotoxicity. The results highlight a wide therapeutic index for Tn P with non-lethal and safe doses rom 1 nM to 10 μM, without causing neurotoxicity or cardiotoxic effect. The low frequencyf abnormalities by Tn P was associated with high safety of the molecule and the developing embryo's ability to process and eliminate it. Tn P crossed the blood-brain barrier without disturbing the normal architecture of forebrain, midbrain and hindbrain. Our data reinforce the importance of zebrafish as an accurate investigative toxicology model to assess acute toxicity as well as cardiotoxicity and neurotoxicity of molecules in the preclinical phase of development. (© 2020 Published by Elsevier B.V.) |
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فهرسة مساهمة: | Keywords: Drug safety; Preclinical analysis; TnP peptide; Toxicology assessments; Zebrafish |
تواريخ الأحداث: | Date Created: 20201228 Latest Revision: 20201229 |
رمز التحديث: | 20240628 |
مُعرف محوري في PubMed: | PMC7750688 |
DOI: | 10.1016/j.toxrep.2020.12.004 |
PMID: | 33364179 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2214-7500 |
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DOI: | 10.1016/j.toxrep.2020.12.004 |