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Chuenlei Parng

Publications and source records attributed to Chuenlei Parng.

6 recordsLinked to original sources
PubMed2006

A zebrafish assay for identifying neuroprotectants in vivo.

In this study, we developed an in vivo method to determine drug effects on oxidation-induced apoptosis in the zebrafish brain caused by treatment with L-hydroxyglutaric acid (LGA). We confirmed that LGA-induced apoptosis was caused by oxidation by examining the presence of an oxidative product, nitrotyrosine. Next, we examined the effects of 14 characterized neuroprotectants on LGA-treated zebrafish, including: D-methionine (D-Met), Indole-3-carbinol, deferoxamine (DFO), dihydroxybenzoate (DHB), deprenyl, L-NAME (N(G)-nitro-L-arginine methyl ester), n-acetyl L-cysteine (L-NAC), 2-oxothiazolidine-4-carboxylate (OTC), lipoic acid, minocycline, isatin, cortisone, ascorbic acid and alpha-tocopherol. Eleven of 14 neuroprotectants and 7 of 7 synthetic anti-oxidants exhibit significant protection in zebrafish. Buthionine sulfoximine (BSO), used as a negative control, exhibited no significant protective effects. In addition, three blood-brain barrier (BBB) impermeable compounds exhibited no significant effects. Our results in zebrafish were similar to results reported in mammals supporting the utility of this in vivo method for identifying potential neuroprotective anti-oxidants.

Acridines↗
PubMed2005

The use of zebrafish for assessing ototoxic and otoprotective agents.

Zebrafish and other fish exhibit hair cells in the lateral-line neuromasts which are structurally and functionally similar to mammalian inner ear hair cells. To facilitate drug screening for ototoxic or otoprotective agents, we report a straightforward, quantitative in vivo assay to determine potential ototoxicity of drug candidates and to screen otoprotective agents in zebrafish larva. In this study, a fluorescent vital dye, DASPEI (2-(4-(dimethylamino)styryl)-N-ethylpyridinium iodide), was used to stain zebrafish hair cells in vivo and morphometric analysis was performed to quantify fluorescence intensity and convert images to numerical endpoints. Various therapeutics, including gentamicin, cisplatin, vinblastine sulfate, quinine, and neomycin, which cause ototoxicity in humans, also resulted in hair cell loss in zebrafish. In addition, protection against cisplatin-induced ototoxicity was observed in zebrafish larva co-treated with cisplatin and different antioxidants including, glutathione (GSH), allopurinol (ALO), N-acetyl l-cysteine (l-NAC), 2-oxothiazolidine-4-carboxylate (OTC) and d-methionine (d-MET). Our data indicate that results of ototoxicity and otoprotection in zebrafish correlated with results in humans, supporting use of zebrafish for preliminary drug screening.

Animals↗
PubMed2005

In vivo zebrafish assays for toxicity testing.

Toxicity, due to complications of in vivo adsorption, distribution, metabolism and excretion (ADME), is a major cause of failure during drug development; many drugs shown to be safe in cell culture prove toxic in animal studies. Effective in vivo toxicity screening early in the development process can reduce the number of compounds that progress to laborious and costly late-stage animal testing. The transparent zebrafish provides accessibility to internal organs, tissues and even cells, and has emerged as an invaluable model organism for toxicity testing and drug discovery. Straightforward in vivo zebrafish assays can serve as an intermediate step between cell-based and mammalian testing, thus streamlining the drug development time-line.

Animals↗
PubMed2002

Zebrafish: a preclinical model for drug screening.

The zebrafish embryo has become an important vertebrate model for assessing drug effects. It is well suited for studies in genetics, embryology, development, and cell biology. Zebrafish embryos exhibit unique characteristics, including ease of maintenance and drug administration, short reproductive cycle, and transparency that permits visual assessment of developing cells and organs. Because of these advantages, zebrafish bioassays are cheaper and faster than mouse assays, and are suitable for large-scale drug screening. Here we describe the use of zebrafish bioassays for assessing toxicity, angiogenesis, and apoptosis. Using 18 chemicals, we demonstrated that toxic response, teratogenic effects, and LC(50) in zebrafish are comparable to results in mice. The effects of compounds on various organs, including the heart, brain, intestine, pancreas, cartilage, liver, and kidney, were observed in the transparent animals without complicated processing, demonstrating the efficiency of toxicity assays using zebrafish embryos. Using endogenous alkaline phosphatase staining and a whole-animal enzyme assay, we demonstrated that SU5416 and flavopiridol, compounds shown to have antiangiogenic effects in mammals, inhibit blood vessel growth in zebrafish, and this bioassay is suitable for high-throughput screening using a 96-well microplate reader. We also demonstrated that in vivo acridine orange staining can be used to visualize apoptotic events in embryos treated with brefeldin A, neomycin, or caspase inhibitors. After in vivo staining, acridine orange can be extracted and quantitated using a fluorescence microplate reader, providing a screening system for agents that modulate apoptosis.

Acridine Orange↗
PubMedDate not supplied

Neurotoxicity assessment using zebrafish.

INTRODUCTION: Transparency is a unique attribute of zebrafish that permits direct assessment of drug effects on the nervous system using whole mount antibody immunostaining and histochemistry. METHODS: To assess pharmacological effects of drugs on the optic nerves, motor neurons, and dopaminergic neurons, we performed whole mount immunostaining and visualized different neuronal cell types in vivo. In addition, we assessed neuronal apoptosis, proliferation, oxidation and the integrity of the myelin sheath using TUNEL staining, immunostaining and in situ hybridization. The number of dopaminergic neurons was examined and morphometric analysis was performed to quantify the staining signals for myelin basic protein and apoptosis. RESULTS: We showed that compounds that induce neurotoxicity in humans caused similar neurotoxicity in zebrafish. For example, ethanol induced defects in optic nerves and motor neurons and affected neuronal proliferation; 6-hydroxydopamine caused neuronal oxidation and dopaminergic neuron loss; acrylamide induced demyelination; taxol, neomycin, TCDD and retinoic acid induced neuronal apoptosis. DISCUSSION: Effects of drug treatment on different neurons can easily be visually assessed and quantified in intact animals. These results support the use of zebrafish as a predictive model for assessing neurotoxicity.

Acrylamide↗