Nifedipine toxicity is exacerbated by acetyl l-carnitine but alleviated by low-dose ketamine in zebrafish in vivo.

Calcium channel blocker (CCB) poisoning is a common and sometimes life-threatening emergency. Our previous studies have shown that acetyl l-carnitine (ALCAR) prevents cardiotoxicity and developmental toxicity induced by verapamil, a CCB used to treat patients with hypertension. Here, we tested whether toxicities of nifedipine, a dihydropyridine CCB used to treat hypertension, can also be mitigated by co-treatment with ALCAR.

Ketamine-induced attenuation of reactive oxygen species in zebrafish is prevented by acetyl l-carnitine in vivo.

Ketamine, an anesthetic, is a non-competitive antagonist of the calcium-permeable N-methyl-d-aspartate (NMDA) receptor. High concentrations of ketamine have been implicated in cardiotoxicity and neurotoxicity. Often, these toxicities are thought to be mediated by reactive oxygen species (ROS).

N-acetylcysteine prevents ketamine-induced adverse effects on development, heart rate and monoaminergic neurons in zebrafish.

N-acetylcysteine, a precursor molecule of glutathione, is an antioxidant. Ketamine, a pediatric anesthetic, has been implicated in cardiotoxicity and neurotoxicity including modulation of monoaminergic systems in mammals and zebrafish. Here, we show that N-acetylcysteine prevents ketamine's adverse effects on development and monoaminergic neurons in zebrafish embryos.

Mechanistic studies on ketamine-induced mitochondrial toxicity in zebrafish embryos.

Ketamine, a phencyclidine derivative, is an antagonist of the Ca-permeable N-methyl-d-aspartate (NMDA)-type glutamate receptors. It is a pediatric anesthetic and has been implicated in developmental neurotoxicity. Ketamine has also been shown to deplete ATP in mammalian cells.

Cyclosporine exacerbates ketamine toxicity in zebrafish: Mechanistic studies on drug-drug interaction.

Cyclosporine A (CsA) is an immunosuppressive drug commonly used in organ transplant patients to prevent allograft rejections. Ketamine is a pediatric anesthetic that noncompetitively inhibits the calcium-permeable N-methyl-d-aspartic acid receptors. Adverse drug-drug interaction effects between ketamine and CsA have been reported in mammals and humans.

Acetyl L-carnitine targets adenosine triphosphate synthase in protecting zebrafish embryos from toxicities induced by verapamil and ketamine: An in vivo assessment.

Verapamil is a Ca channel blocker and is highly prescribed as an anti-anginal, antiarrhythmic and antihypertensive drug. Ketamine, an antagonist of the Ca -permeable N-methyl-d-aspartate-type glutamate receptors, is a pediatric anesthetic. Previously we have shown that acetyl l-carnitine (ALCAR) reverses ketamine-induced attenuation of heart rate and neurotoxicity in zebrafish embryos.

Distinct effects of ketamine and acetyl L-carnitine on the dopamine system in zebrafish.

Ketamine, a noncompetitive N-methyl-D-aspartic acid (NMDA) receptor antagonist is commonly used as a pediatric anesthetic. We have previously shown that acetyl L-carnitine (ALCAR) prevents ketamine toxicity in zebrafish embryos. In mammals, ketamine is known to modulate the dopaminergic system.

Opposing effects of ketamine and acetyl L-carnitine on the serotonergic system of zebrafish.

Ketamine, a pediatric anesthetic, is a noncompetitive N-methyl-D-aspartic acid (NMDA) receptor antagonist. Studies show that ketamine is neurotoxic in developing mammals and zebrafish. In both mammals and zebrafish, acetyl L-carnitine (ALCAR) has been shown to be protective against ketamine toxicity.

Developmental toxicity assay using high content screening of zebrafish embryos.

Typically, time-consuming standard toxicological assays using the zebrafish (Danio rerio) embryo model evaluate mortality and teratogenicity after exposure during the first 2 days post-fertilization. Here we describe an automated image-based high content screening (HCS) assay to identify the teratogenic/embryotoxic potential of compounds in zebrafish embryos in vivo. Automated image acquisition was performed using a high content microscope system.

K114 inhibits A-beta aggregation and inflammation in vitro and in vivo in AD/Tg mice.

Alzheimer's disease (AD) is the most common age related human neurodegenerative disorder. The major histopathological characteristics of the AD brain are extracellular amyloid-beta (Aβ) peptide loaded plaques and intraneuronal neurofibrillary tangles made of phosphorylated tau proteins. Amyloid plaques consist primarily of aggregated Aβ1-42 and Aβ1-40 peptides.

Efficacy and toxicity of clioquinol treatment and A-beta42 inoculation in the APP/PSI mouse model of Alzheimer's disease.

Alzheimer's disease (AD), the most common human neurodegenerative disease, is characterized pathologically by numerous deposits of amyloid plaques in the brain. Systemic administration of clioquinol (CQ) and inoculation with amyloid-beta42 (Aβ42) vaccines have been demonstrated to significantly inhibit deposits of amyloid in AD brains. However, each of these treatments has also been reported to be neurotoxic.

Characterization of myelin pathology in the hippocampal complex of a transgenic mouse model of Alzheimer's disease.

We have characterized the myelin changes observed within the hippocampal complex (HC) of a transgenic (Tg) mouse model of Alzheimer's disease (AD). Individual myelinated fibers were labeled with Black-Gold II while amyloid plaques were labeled with either Congo Red or Pan-A-beta immunofluoresence. Myelinated fibers were never seen passing through amyloid plaques in any region, while conspicuous myelin pathology was seen within, and immediately adjacent to, the amyloid plaques in the HC of the AD-Tg mouse.