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Most of the innovative drugs with important therapeutic benefits are not approved or are removed from the clinical practice owing to drug-induced toxicity. The kidneys are one of the most important target organs of drug toxicity as they play an important role in drug excretion and drug metabolism. More specifically, the proximal tubule, which is a part of the nephrons of the kidney, is very sensitive to any drug insult as it reabsorbs and secretes drugs and metabolites, meaning that it is continuously exposed to high concentrations of toxins. Therefore, the kidney is more susceptible to be damaged by drugs, which ultimately leads to drug-induced kidney injury (DIKI). The DIKI progressing is reversible at early stage and the function of kidney can be recovered if DIKI is discovered and treated promptly. Otherwise, irreversible damage to the kidney will occur with the DIKI progressing to the late stage. Thus, discriminative detection of DIKI at early and late stages has important significance for predicting the drug nephrotoxicity, adjusting the dosage regimen, and improving the success rate of new drug research.
Recently, zebrafish have been used as an alternative experimental animal model for mammals. Because the cell types present in the zebrafish pronephros and mesonephros closely resemble those found in higher vertebrates, zebrafish have also been used to study kidney function, drug-induced damage and repair mechanisms. In addition, as zebrafish larvae and juvenile fish are small in size and hence can be arrayed in 24- or 96-well plates, zebrafish-based disease models have become attractive as rapid drug discovery platforms over the last decade.
Figure 1. Morphological and functional assessment of DIKI.
Zebrafish is not only an ideal model in developmental biology research but also for the examination of organ toxicity. With years of experience and advanced technologies, Creative Biogene has developed several approaches to utilize zebrafish in nephrotoxicity screening. We have examined the feasibility of zebrafish as an alternative animal model to mammals for evaluating DIKI. And we have improved this screening assay and technology, and performed a large in vivo high-content screening experiment with the aim to identify approved drugs with adverse effects on the kidney in zebrafish.
Contact us to learn more about our nephrotoxicity assessment services.
References
For research use only. Not intended for any clinical use.
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