ReviewGene to ScreenZebrafish: a predictive model for assessing drug-induced toxicity
Section snippets
Cardiotoxicity assessment in zebrafish
Unforeseen cardiotoxicity is a major problem that can result in drug withdrawal. In 2004, rofecoxib (Vioxx), Merck's blockbuster antiarthritic drug was removed from the market because of increased risk of heart attack and stroke. Another example, propulsid (Cisapride), an oral gastrointestinal prokinetic agent, has been associated with ∼400 adverse cardiac events (arrhythmias) and has resulted in more than 80 deaths in the USA 6, 7. These problems with cardiotoxicity led to the removal of
Hepatotoxicity assessment in zebrafish
Drug-induced liver injury has been recognized by the pharmaceutical industry as a major toxicological problem. Tests that are useful for evaluating drug-induced hepatotoxicity in laboratory animals fall into four primary categories: (1) serum enzyme tests; (2) hepatic excretory tests; (3) assessment of alterations in the chemical constituents of the liver and (4) histological analysis. Tests for assessing repair and recovery of liver parenchyma and apoptosis are also used to study the effects
Neurotoxicity assessment in zebrafish
Neurotoxicity is another leading cause of drug withdrawal and examples of costly high-profile cases of neurotoxicity include diamthazole, vinyl chloride and clioquinol [29]. Neurotoxicity profiles of numerous approved drugs are incomplete and many cause neurotoxic side effects 29, 30, 31. Increasing public concern about drug- and chemical-induced neurotoxicity and the inadequacy of current toxicological testing requirements resulted in initiation of a US Congressional review of Federal research
Developmental toxicity assessment in zebrafish
After the teratogenic effects of thalidomide were recognized in 1966, the FDA established protocols to be used for assessing drug effects on reproduction and development before approval for human use. In addition, because of concerns about chemicals in human food, the EPA issued similar guidelines for pesticides in 1982 and for industrial chemicals in 1985. According to current international guidelines, developmental toxicity testing involves exposing pregnant animals, usually rats or rabbits,
Summary
Zebrafish has been shown to be a predictive animal model for assessing drug toxicity and safety. Assessment of a large number of compounds from diverse drug classes is necessary to further validate the model. Although it is unclear how ADME after drug delivery in fish water compares to ADME after delivery by other routes of administration, performance of studies in adult zebrafish using conventional drug delivery methods such as injection and intubation promises to increase the use of this
Conflict of interest
Both authors are employees of Phylonix. Ms McGrath is also an inventor of patents assigned to Phylonix.
References (60)
Zebrafish apoptosis assays for drug discovery
Methods Cell Biol.
(2004)- et al.
The use of zebrafish for assessing ototoxic and otoprotective agents
Hearing Res.
(2005) Cardiotoxicity of new antihistamines and cisapride
Toxicol. Lett.
(2002)Validation of a [3H]astemizole binding assay in HEK293 cells expressing HERG K+ channels
J. Pharmacol. Sci.
(2004)Zebrafish embryos express an orthologue of HERG and are sensitive toward a range of QT-prolonging drugs inducing severe arrhythmia
Toxicol. Appl. Pharmacol.
(2003)The long QT syndrome: ion channel diseases of the heart
Mayo Clin. Proc.
(1998)Cardiac repolarization: current knowledge, critical gaps, and new approaches to drug development and patient management
Am. Heart J.
(2002)Nonclinical proarrhythmia models: predicting Torsades de Pointes
J. Pharmacol. Toxicol. Methods
(2005)Acquired QT interval prolongation and HERG: implications for drug discovery and development
Eur. J. Pharmacol.
(2004)Uptake, toxicity, and effects on detoxication enzymes of atrazine and trifluoroacetate in embryos of zebrafish
Ecotoxicol. Environ. Saf.
(2000)
Expression of PXR, CYP3A and MDR1 genes in liver of zebrafish
Comp. Biochem. Physiol. C: Toxicol. Pharmacol.
Constitutive and xenobiotics-induced expression of a novel CYP3A gene from zebrafish larva
Toxicol. Appl. Pharmacol.
Whole zebrafish cytochrome P450 microplate assays for assessing drug metabolism and drug safety
Toxicologist
Hepatic steatosis in zebrafish (Brachydanio rerio) induced by long-term exposure to gamma-hexachlorocyclohexane
Ecotoxicol. Environ. Saf.
The zebrafish as a model system for assessing the reinforcing properties of drugs of abuse
Methods
Neurotoxicity assessment using zebrafish
J. Pharmacol. Toxicol. Methods
A zebrafish assay for identifying neuroprotectants in vivo
Neurotoxicol. Teratol.
Degeneration and gliosis in rat retina and central nervous system following 3,3″-iminodipropionitrile exposure
Brain Res.
Structural and functional characterization of the zebrafish gene for glial fibrillary acidic protein, GFAP
Gene
The neonate-6-hydroxydopamine-lesioned rat: a model for clinical neuroscience and neurobiological principles
Brain Res. Brain Res. Rev.
The teleostean (zebrafish) dopaminergic system ascending to the subpallium (striatum) is located in the basal diencephalons (posterior tuberculum)
Brain Res.
Connections of the ventral telencephalon and tyrosine hydroxylase distribution in the zebrafish brain (Danio rerio) lead to identification of an ascending dopaminergic system in a teleost
Brain Res. Bull.
Apoptosis: a target for neuroprotection
Therapie
Peripheral neuropathy: a persisting challenge in paclitaxel-based regimes
Eur. J. Cancer
Pentylenetetrazole induced changes in zebrafish behavior, neural activity and c-fos expression
Neuroscience
Zebrafish: a preclinical model for drug screening
Assay Drug Dev. Technol.
In vivo zebrafish assays for toxicity testing
Curr. Opin. Drug Discov. Dev.
Human melanoma cells transplanted into zebrafish proliferate, migrate, produce melanin, form masses and stimulate angiogenesis in zebrafish
Angiogenesis
Organogenesis – heart and blood formation from the zebrafish point of view
Science
Functional and morphological evidence for a ventricular conduction system in zebrafish and Xenopus hearts
Am. J. Physiol. Heart Circ. Physiol.
Cited by (451)
Potential of the Blue Calm® food supplement in the treatment of alcohol withdrawal-induced anxiety in adult zebrafish (Danio rerio)
2024, Neurochemistry InternationalN-nitrosodimethylamine exposure to zebrafish embryos/larvae causes cardiac and spinal developmental toxicity
2024, Comparative Biochemistry and Physiology Part - C: Toxicology and PharmacologyThe posterity of Zebrafish in paradigm of in vivo molecular toxicological profiling
2024, Biomedicine and PharmacotherapyThe invisible Threat: Assessing the reproductive and transgenerational impacts of micro- and nanoplastics on fish
2024, Environment InternationalEcotoxicological assessment of Cu-rich acid mine drainage of Sulitjelma mine using zebrafish larvae as an animal model
2024, Ecotoxicology and Environmental SafetyTo be or not to be plastics? Protein modulation and biochemical effects in zebrafish embryos exposed to three water-soluble polymers
2024, Science of the Total Environment