Elucidating mechanism of drug induced toxicity
Instead of other fish species, zebrafish adults are only approximately 1-1.5 inches long.
Also zebrafish have been utilized as a laboratory species for quite some time so the optimum breeding and maintenance conditions have been well determined.
The advantages of the zebrafish both in identifying endpoints of toxicity and in elucidating mechanism of toxicity are highlighted.
By using zebrafish to study vertebrate development that mutations are relatively easy to obtain and to screen.
The zebrafish embryos may be more or less sensitive to toxins than the other organisms, therefore the lowest value can be considered as the starting point.
The method is based on using a minimum of five test concentration as well as appropriate control with individual embryos per exposure concentration.
Lethal dose 50 (LD50) is the measurement used in toxicology studies to determine the potential impact of toxic substance on different types of organism.
The LD50 depend on the route of entry into the body of the organism being tested.
In severalties to larger species, the minute size of the larval and adult zebrafish minimizes quantities of lab ware and chemicals, both for treating and maintaining live fishes and also costs through low quantities of dosing substance and performing various assays.
In addition to these another important feature of the zebrafish embryos are fecundity and transparent embryos.
Covalent bonding thus allows high potency to be routinely achieved in compounds of low molecular mass, along with all the beneficial pharmaceutical properties that are associated with small size (Smith, Zhang, Leach, & Houk, 2009) Covalent inhibitors can be designed to target a nucleophile that is unique or rare across a protein family (Singh et al., 1997)(Cohen et al., 2005)(Singh et al., 2010)(Liu et al., 2013), thereby ensuring that covalent bond formation cannot occur with most other family members.
This approach can lead to high selectivity against closely related proteins because although the inhibitor might bind transiently to the active sites of such proteins, it will not covalently label them if they lack the targeted nucleophilic residue in the appropriate position.