Search PubMed⌕ Search
Home/Archive/PubMed

PubMed · 8137927

Amiodarone-induced hypercholesterolemia is associated with a decrease in liver LDL receptor mRNA.

F Hudig·O Bakker·W M Wiersinga
View original source ↗Export metadata ↓

Abstract

Amiodarone decreases plasma and tissue triiodothyronine (T3) and increases plasma cholesterol levels resembling changes seen during hypothyroidism. To elucidate the mechanism of amiodarone-induced hypercholesterolemia we investigated gene expression of three key proteins in cholesterol metabolism (cholesterol 7 alpha-hydroxylase, LDL receptor, HMG-CoA reductase) in livers of rats. Animals were treated with amiodarone or propylthiouracil (to induce mild hypothyroidism). The LDL receptor mRNA was downregulated (approximately 50%) in both amiodarone-treated and hypothyroid animals, while the other mRNA remained unchanged after 14-day treatment. The results suggest that amiodarone-induced hypercholesterolemia is associated with decreased LDL receptor mRNA levels.

Explore related subjects

AmiodaroneAnimalsCholesterol 7-alpha-HydroxylaseHydroxymethylglutaryl CoA ReductasesHypercholesterolemiaLiverMalePropylthiouracilRNA, MessengerRatsRats, WistarReceptors, LDLTime FactorsJournal Article

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

F Hudig, O Bakker, W M Wiersinga. 1994-03-14. Amiodarone-induced hypercholesterolemia is associated with a decrease in liver LDL receptor mRNA.. https://doi.org/10.1016/0014-5793(94)80245-9

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed1996

Amiodarone-induced pulmonary fibrosis in Fischer 344 rats.

Amiodarone is a potent antiarrhythmic agent with a number of side-effects, the most serious being the development of pulmonary toxicity. The purpose of the study was to determine if a single intratracheal instillation of amiodarone would induce pulmonary fibrosis and associated functional changes in rats. Female Fischer 344 rats were given a single intratracheal instillation of 200 microliters containing 1.25 mg amiodarone (n = 9) while the control group received an equivalent volume of sterile water (n = 8). After 6 weeks, pulmonary function tests, lung hydroxyproline measurements and lung histology were performed. The amiodarone-treated animals showed a significant reduction in the coefficient of diffusion (kCO) and a significant increase in lung hydroxyproline levels as compared to the control group. The treated group had abnormal histology including areas of septal thickening with cellular infiltration of the interstitial and alveolar spaces, whereas the control group had normal histology. These observations suggest that the intratracheal instillation route of amiodarone treatment produces a fibrotic response in rats that can be measured physiologically, biochemically and histologically. This model may aid in the elucidation of the mechanism of amiodarone-induced pulmonary toxicity (AIPT)./ABS.

Amiodarone↗
PubMed1996

[Early diagnosis of amiodarone-induced pulmonary toxicity: are repeated lung function tests of any value?].

Amiodarone therapy for certain life-threatening cardiac arrhythmias is associated with numerous side and adverse effects, of which pulmonary toxicity is one of the most serious adverse reactions. It appears to be generally accepted that amiodarone-induced pulmonary toxicity (APT) is associated with considerable morbidity and mortality. Based on the assumption that detection of APT in an asymptomatic phase would improve the prognosis for these patients, the value of monitoring for toxic effects with various paraclinical tests has been extensively studied. This article summarizes current knowledge of the pulmonary complications of amiodarone therapy with emphasis on the usefulness of pulmonary function tests in the detection of APT. Based on the findings in the published studies, it appears that changes in pulmonary function, including diffusion capacity, over time do not identify patients at risk for development of APT. It is suggested that it is worthwhile to obtain two or three measurements of pulmonary function, including diffusion capacity, within the first few months of therapy in order to establish the variation in the individual patient. When a stable maintenance dose has been reached, subsequent testing should be reserved for patients who develop new or progressive pulmonary symptoms or radiographic infiltrates.

Amiodarone↗
PubMed1996

Stepwise binary gradient high-performance liquid chromatographic system for routine drug monitoring.

Drug therapy is usually optimized by concentration measurement in patient serum. High-performance liquid chromatography (HPLC) is one of the most important analytical techniques used for therapeutic drug monitoring (TDM) of drugs for which no immunoassay kits are available. HPLC has been frequently used for screening purposes in toxicology, too. The Merck Tox Screening System (MTSS) has been developed for the identification of substances by a combination of gradient HPLC with diode-array detection and identification with a database system. For routine TDM an isocratic HPLC system is more suitable because of shorter analysis time, better reproducibility of retention index and better precision of results. Therefore we defined a set of methods in steps of 10% of the two MTSS eluents. Three examples are shown: Amiodarone, Indometacine and Thiopental. New applications to test for other substances can be transferred to an isocratic system after a complete MTSS gradient run.

Amiodarone↗