Amiodarone is prescribed for the treatment and prevention of irregular heartbeats. Although effective in clinical practice, the long-term use of amiodarone has many unwanted side effects, including cardiac, pulmonary, hepatic, and neurological toxicities. Our objective was to elucidate effects of amiodarone exposure on the cholesterol metabolism in cultured neuronal and non-neuronal cells and in individuals taking amiodarone. We observed that amiodarone increases distinct cholesterol precursors in different cell types in a dose-dependent manner. In liver and kidney cell lines, amiodarone causes increase in desmosterol levels, and in primary cortical neurons and astrocytes, amiodarone increases zymosterol, zymostenol, and 8-dehydrocholesterol (8-DHC). We conclude that amiodarone inhibits two enzymes in the pathway, emopamil binding protein (EBP) and dehydrocholesterol reductase 24 (DHCR24). Cortical neurons and astrocytes are more sensitive to amiodarone than liver and kidney cell lines. We confirmed the inhibition of EBP enzyme by analyzing the sterol intermediates in EBP-deficient Neuro2a cells versus amiodarone-treated control Neuro2a cells. To determine if the cell culture experiments have clinical relevance, we analyzed ser...Continue Reading
The effects of amiodarone, an alpha and beta receptor antiagonist, on adrenergic transmission in the cat spleen
Correlation of amiodarone dosage, heart rate, QT interval and corneal microdeposits with serum amiodarone and desethylamiodarone concentrations
Amiodarone: correlation of serum concentration with suppression of complex ventricular ectopic activity
Steady-state serum amiodarone concentrations: relationships with antiarrhythmic efficacy and toxicity
Neurotoxic action of some antiarrhythmic agents: comparative effects of propafenone, lidocaine and amiodarone on leech Retzius nerve cell
Evaluation of human blood lymphocytes as a model to study the effects of drugs on human mitochondria. Effects of low concentrations of amiodarone on fatty acid oxidation, ATP levels and cell survival
Yeast sterol C8-C7 isomerase: identification and characterization of a high-affinity binding site for enzyme inhibitors
High affinity of sigma 1-binding sites for sterol isomerization inhibitors: evidence for a pharmacological relationship with the yeast sterol C8-C7 isomerase
Elevation of high-density lipoprotein cholesterol in humans during long-term therapy with amiodarone
Abnormal sterol metabolism in patients with Conradi-Hünermann-Happle syndrome and sporadic lethal chondrodysplasia punctata
Cloning of an emopamil-binding protein (EBP)-like protein that lacks sterol delta8-delta7 isomerase activity
Developmental delay associated with normal thyroidal function and long-term amiodarone therapy during fetal and neonatal life
An oxysterol biomarker for 7-dehydrocholesterol oxidation in cell/mouse models for Smith-Lemli-Opitz syndrome.
Conradi-Hünermann-Happle syndrome in males vs. MEND syndrome (male EBP disorder with neurological defects)
Phospholipidosis in rats treated with amiodarone: serum biochemistry and whole genome micro-array analysis supporting the lipid traffic jam hypothesis and the subsequent rise of the biomarker BMP
A highly sensitive method for analysis of 7-dehydrocholesterol for the study of Smith-Lemli-Opitz syndrome.
The Effect of Small Molecules on Sterol Homeostasis: Measuring 7-Dehydrocholesterol in Dhcr7-Deficient Neuro2a Cells and Human Fibroblasts
Inhibitors of 7-Dehydrocholesterol Reductase: Screening of a Collection of Pharmacologically Active Compounds in Neuro2a Cells
Hepatic Amiodarone Lipotoxicity Is Ameliorated by Genetic and Pharmacological Inhibition of Endoplasmatic Reticulum Stress
Identification and characterization of prescription drugs that change levels of 7-dehydrocholesterol and desmosterol.
Potential involvement of the microbiota-gut-brain axis in the neurotoxicity of triphenyl phosphate (TPhP) in the marine medaka (Oryzias melastigma) larvae.
Antiarrhythmic Agents: Mechanisms of Action
Understanding the mechanism of action of antiarrhythmic agents is essential in developing new medications as treatment of cardiac arrhythmias is currently limited by the reduced availability of safe and effective drugs. Discover the latest research on Antiarrhythmic Agents: Mechanism of Action here.
Astrocytes are glial cells that support the blood-brain barrier, facilitate neurotransmission, provide nutrients to neurons, and help repair damaged nervous tissues. Here is the latest research.