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Expression profiling of rat heart and blood after amiodarone treatment

ABSTRACT: In the present study, an oligonucleotide microarray platform was used to compare expression profiles of heart and blood in rats treated with amiodarone against respective controls. Male Sprague-Dawley (CD) rats, which were 10 weeks old and weighed 290-320 grams at the beginning of the study, have been treated for ten days with amiodarone by oral route at a dose of 300mg/Kg/die. The study has been constituted by a control group, which received the vehicle (methylcellulose 1%, w/v), and by a treatment group (10 animals for both groups). For each tissue sample, total RNA has been individually extracted and evaluated. For each tissue, three pools/group (2 pools composed of 3 animals and the last one by 4) have been used for microarray analysis. A modulation of 600 genes in heart and 8300 genes in blood has been obtained.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE24213 | GEO | 2015/03/23

SECONDARY ACCESSION(S): PRJNA132947

REPOSITORIES: GEO

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Project description:Amiodarone reversibly decreases sodium-iodide symporter mRNA expression at therapeutic concentrations and induces antioxidant responses at supraphysiological concentrations in cultured human thyroid follicles Amiodarone, a potent antiarrhythmic agent, is a highly active oxidant, exerting cytotoxic effects on thyrocytes at pharmacological concentrations. Patients receiving amiodarone usually remain euthyroid, but occasionally develop thyroid dysfunction, such as amiodarone-associated hypothyroidism or amiodarone-induced thyrotoxicosis. To elucidate the mechanism by which amiodarone elicits thyroid dysfunction, human thyroid follicles were cultured with TSH and amiodarone at therapeutic (1-2 microM) and pharmacological (10-20microM) concentrations, and the drug-induced effect on whole human gene expression was analyzed by cDNA microarray. Amiodarone at 1-2microM decreased the expression level of the sodium-iodide symporter (NIS) to nearly half, but did not affect genes participating in thyroid hormonogenesis (thyroid peroxidase, thyroglobulin, pendrin, NADPH oxidase). Higher concentrations (10-20 microM) decreased the expression of all these genes, accompanied by increased expression of antioxidant proteins such as heme oxygenase 1 and ferritin. When thyroid follicles obtained from a patient with Graves’ disease who had been treated with amiodarone for 2 months before thyroidectomy were cultured in amiodarone-free medium, TSH-induced thyroid function was intact, suggesting that amiodarone at a maintenance dose did not elicit any cytotoxic effect on thyrocytes. The ultrastructural features of cultured thyroid follicles were compatible with these in vitro findings. These in vitro and ex vivo findings suggest that patients taking maintenance doses of amiodarone usually remain euthyroid, probably due to escape from the Wolff-Chaikoff effect mediated by decreased expression of NIS mRNA. Furthermore, amiodarone is not cytotoxic for thyrocytes at therapeutic concentrations but elicits cytotoxicity through oxidant activity at supra-physiological concentrations. Keywords: Cultured human thyroid follicles

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Expression profiling of rat heart and blood after amiodarone treatment

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