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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Early preclinical screening using zebrafish (Danio rerio) reveals the safety of the candidate anti-inflammatory therapeutic agent TnP

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Author(s):
Batista-Filho, Joao [1, 2] ; Falcao, Maria Alice Pimentel [2] ; Maleski, Adolfo Luis Almeida [1, 2] ; Soares, Amanda Beatriz Silva [2] ; Balan-Lima, Leticia [2] ; Disner, Geonildo Rodrigo [2] ; Lima, Carla [2] ; Lopes-Ferreira, Monica [2]
Total Authors: 8
Affiliation:
[1] Butantan Inst, Postgrad Program Toxinol, Sao Paulo, SP - Brazil
[2] Butantan Inst, Lab Appl Toxinol CeTICs FAPESP, Immunoregulat Unit, Vital Brazil Ave 1500, BR-05503009 Sao Paulo, SP - Brazil
Total Affiliations: 2
Document type: Journal article
Source: TOXICOLOGY REPORTS; v. 8, p. 13-22, 2021.
Web of Science Citations: 2
Abstract

The patented anti-inflammatory peptide TnP had its effectiveness recently confirmed in vivo in a murine model of multiple sclerosis and asthma. In this work, the safety of the TnP was evaluated in investigative toxicology tests using zebrafish (Danio rerio) as a model. We conducted the OECD \#236 test to investigate effects of the TnP 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 TnP with non-lethal and safe doses rom 1 nM to 10 mu M, without causing neurotoxicity or cardiotoxic effect. The low frequencyf abnormalities by TnP was associated with high safety of the molecule and the developing embryo's ability to process and eliminate it. TnP 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. (AU)

FAPESP's process: 13/07467-1 - CeTICS - Center of Toxins, Immune-Response and Cell Signaling
Grantee:Hugo Aguirre Armelin
Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC