Effects of amiodarone on 5′-deiodination of thyroxine to tri-iodothyronine in rat myocardium

Ceppi, Jorge A.; Zaninovich, Angel A.

doi:10.1677/joe.0.1210431

Cited by 20 publications

(10 citation statements)

References 12 publications

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“…In rats, long-term AM treatment led to contradictory results with a decrease in plasma TSH concentration associated with an increase in plasma T4 and a decrease in plasma T3 (23) or an increase in plasma TSH secretion (5,24) and TSH subunit synthesis (24). In addition, thyroid hormone induced a fall in TSH secretion that was less pronounced when rats were treated with both AM and TH (24), suggesting a competitive interaction consistent with AM inhibition of T3 binding to nuclear receptors in the anterior pituitary (5).…”

Section: Effects Of Amiodarone (Am)mentioning

confidence: 99%

Dihydropyridine-like effects of amiodarone and desethylamiodarone on thyrotropin secretion and intracellular calcium concentration in rat pituitary

Roussel

Grazzini²,

Guipponi³

et al. 1995

European Journal of Endocrinology

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Amiodarone (AM) and its major metabolite desethylamiodarone (DEA) are structurally similar to biologically active thyroid hormones. Amiodarone therapy is frequently associated with impairment of thyrotropic function, whose mechanisms are still controversial. Besides its effect on nuclear thyroid hormone binding. AM is able to displace dihydropyridine (DH) binding on membrane preparations from several tissues. By perifusing rat pituitary fragments and measuring thyrotropin (TSH) release we examined: the effect of AM on Ca(2+)-dependent and DHP-sensitive potentiation of the TSH response to thyrotropin-releasing hormone (TRH) induced by either triiodothyronine (T3, perifused for only 30 min before a TRH pulse) or by the prepro-TRH peptide 160-169 (PS4); and the effect of DEA on TRH-induced TSH response in the presence or absence of the DHP nifedipine. We show that AM reverses T3 or PS4 potentiation of the TSH response to TRH; this effect is specific because AM does not modify ionomycin potentiation of that response. In contrast, DEA significantly potentiates the TSH response to TRH and the DHP nifedipine reverses that potentiation. We also tested whether AM would change the acute T3-induced increase in intracellular Ca2+ concentration by measuring intracellular Ca2+ ([Ca2+])i with fura-2 imaging on primary cultures of pituitary cells. We show that AM reverses the effect of T3 on [Ca2+]i as well as the PS4-induced increase in [Ca2+]i. In contrast, DEA increases [Ca2+]i and nifedipine reverses this effect. Our results suggest that AM and DEA display DHP-like effects on TRH-induced TSH release, behaving either as a Ca2+ channel blocker (AM) or as a Ca2+ channel agonist (DEA).

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Section: Effects Of Amiodarone (Am)mentioning

confidence: 99%

Dihydropyridine-like effects of amiodarone and desethylamiodarone on thyrotropin secretion and intracellular calcium concentration in rat pituitary

Roussel

Grazzini²,

Guipponi³

et al. 1995

European Journal of Endocrinology

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“…The result¬ ing histograms allowed a clear identification of the radioactive compounds, which were correlated with the stained areas in duplicate strips. Radioactivity in the chromatograms were corrected for the proportion of each radioactive compound present in the Chromatographie runs of the standard solutions as received from the commercial source, and of tissuefree systems incubated concomitantly with the homogenates (Ceppi & Zaninovich, 1989). …”

Section: T4 Deiodination Studiesmentioning

confidence: 99%

Changes induced by cadmium administration on thyroxine deiodination and sulfhydryl groups in rat liver

Paier¹,

Hagmüller²,

Noli³

et al. 1993

Journal of Endocrinology

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The effects of cadmium on 5'-deiodination of thyroxine (T4) by rat liver and on the hepatic concentration of non-protein sulfhydryl groups (NPSH) were studied in Wistar rats of 200-250 g body weight. A group of ten rats was injected with cadmium chloride (300 micrograms/100 g body weight i.p.) daily for 4 days. Another group of six rats received, in addition, dithiothreitol (DTT; 1 mg/100 g body weight i.p.) daily for the same period. A group of eight normal untreated rats served as control. T4 deiodination was also determined in aliquots of liver from untreated rats, with cadmium (2 or 5 mmol/l) and with or without DTT (0, 2.5, 5 or 10 mmol/l) plus 1 microCi 125I-labelled T4. Hepatic NPSH were measured by a colorimetric method employing dithioldinitrobenzoic acid. Homogenates were incubated for 90 min at 37 degrees C and chromatographed in a tertiary amyl alcohol:hexane:ammonia (2 mol/l) (10:1:12) system. Cadmium-injected rats showed a significant (P < 0.01) decrease in T4 deiodination and in the generation of 125I (P < 0.01) and tri-iodothyronine (T3) (P < 0.02). NPSH were also decreased (P < 0.02). Administration of DTT restored T4 deiodination and NPSH to normal. In-vitro addition of cadmium or DTT to normal rat liver homogenates induced similar effects on the degradation of T4. Serum concentrations of T4 (P < 0.01) and T3 (P < 0.01) declined significantly in cadmium-injected rats, whereas DTT administration failed to normalize serum hormone levels. The data suggest that cadmium may have decreased 5'-deiodinating activity through binding to sulfhydryl groups of 5'-deiodinase as it does in other enzymes.(ABSTRACT TRUNCATED AT 250 WORDS)

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“…The counted radioactivity was corrected for the proportion of radioactive compounds other than ( 125 I)T 4 that were present in the chromatographic runs of the commercial solution of ( 125 I)T 4 and of the tissue-free preparations in the manner described previously (Ceppi and Zaninovich 1989).…”

Section: Methodsmentioning

confidence: 99%

Cadmium Inhibits the In Vitro Conversion of Thyroxine to Triiodothyronine in Rat Brown Adipose Tissue

Paier

Pavia

Hansi

et al. 1997

Bulletin of Environmental Contamination and Toxicology

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Effects of amiodarone on 5′-deiodination of thyroxine to tri-iodothyronine in rat myocardium

Cited by 20 publications

References 12 publications

Dihydropyridine-like effects of amiodarone and desethylamiodarone on thyrotropin secretion and intracellular calcium concentration in rat pituitary

Dihydropyridine-like effects of amiodarone and desethylamiodarone on thyrotropin secretion and intracellular calcium concentration in rat pituitary

Changes induced by cadmium administration on thyroxine deiodination and sulfhydryl groups in rat liver

Cadmium Inhibits the In Vitro Conversion of Thyroxine to Triiodothyronine in Rat Brown Adipose Tissue

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