ompound application routes for larval zebrafish. Uptake routes which IRAK1 Species predominate throughout exposure Figure 1. Possible compound application routes for larval zebrafish. Uptake routes which predominate during exposure by by immersion indicated by by arrows, sites for compound microinjection by injection needles. immersion are are indicated arrows, websites for compound microinjection by injection needles.two.2. Metabolism and Excretion zebrafish express drug metabolising enzymes, including phase I enzymes for example Zebrafish Cytochromes P450 (CYPs), as well as sulfo- (SULTs) and UDP-glucuronosyltransferases (SULTs) and UDP-glucuronosyltransferases (UGTs) which are involved in phase xenobiotic metabolism [524]. CYPs are evolution(UGTs) which are involved in phase II II xenobiotic metabolism [524]. CYPs are evolutionary conserved show show orthologs between humans humans and zebrafish [55,56]. ary conserved and and numerous many orthologs among and zebrafish [55,56]. However, On the other hand, genetic syntenya human a human CYP genezebrafish ortholog doesn’t necesgenetic synteny in between between CYP gene and its and its zebrafish ortholog doesn’t necessarily to metabolism from the same substrate and, vice versa, absence of an ortholog sarily lead result in metabolism on the exact same substrate and, vice versa, absence of an may be substituted by other zebrafish CYP enzymes [57]. Also, zebrafish CYP’s ortholog is usually substituted by other zebrafish CYP enzymes [57]. Furthermore, zebrafish exhibit spatiotemporal variations in their expression profiles, using a with powerful in CYP’s exhibit spatiotemporal variations in their expression profiles, strongaincreaseinCYP gene expression right after hatching hatching [579]. In spite of these potential limitations, crease in CYP gene expression right after [579]. Despite these potential limitations, zebrafish CYP orthologs orthologs produce metabolites corresponding to those identified in mamzebrafish CYP frequentlyfrequently create metabolites corresponding to these identimals, mammals, as reviewed by Anselmo de Souza de Souza Richter et al. lately fied inas extensively extensively reviewed by Anselmoet al. [54]. et al. [54]. Richter et al. created a larval a larval in vitro model for forensic toxicology that appropriately appropriately not too long ago developedzebrafishzebrafish in vitro model for forensic toxicology thatpredicted the human metabolites of a new of a new synthetic cannabinoid [60]. inside the 1st the predicted the human metabolites synthetic cannabinoid [60]. Likewise,Likewise, in handful of hours of hours of development start to express LPAR2 custom synthesis metabolic enzymes enzymes for example glufirst handful of improvement zebrafishzebrafish start off to express metabolic such as glutathione-Stransferases (GST’s), whose detoxification capacity in capacity in the mercapturic acid tathione-S-transferases (GST’s), whose detoxificationthe mercapturic acid pathway was demonstrated not too long ago in embryos and embryos and larvae exposed towards the model 2,4pathway was demonstrated lately in larvae exposed towards the model GST substrateGST dinitrochlorobenzene [613]. Even though elimination of xenobiotics of xenobiotics from the husubstrate 2,4-dinitrochlorobenzene [613]. Whilst elimination in the human body takes placebody takes location by clearance bile/faeces as well as the lungs, in zebrafish, bile production man by clearance by way of the kidneys, by means of the kidneys, bile/faeces and also the lungs, in zebrafish, and gills, which serves as a significant respiratory organ, are certainly not totally functional throughout the initial four a