Early preclinical screening using zebrafish () reveals the safety of the candidate anti-inflammatory therapeutic agent P.

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