Differential involvement of various sources of reactive oxygen species in thyroxin-induced hemodynamic changes and contractile dysfunction of the heart and diaphragm muscles

Free Radical Biology & Medicine
Mohammad T ElnakishPaul M L Janssen

Abstract

Thyroid hormones are key regulators of basal metabolic state and oxidative metabolism. Hyperthyroidism has been reported to cause significant alterations in hemodynamics, and in cardiac and diaphragm muscle functions, all of which have been linked to increased oxidative stress. However, the definite source of increased reactive oxygen species (ROS) in each of these phenotypes is still unknown. The goal of the current study was to test the hypothesis that thyroxin (T4) may produce distinct hemodynamic, cardiac, and diaphragm muscle abnormalities by differentially affecting various sources of ROS. Wild-type and T4 mice with and without 2-week treatments with allopurinol (xanthine oxidase inhibitor), apocynin (NADPH oxidase inhibitor), L-NIO (nitric oxide synthase inhibitor), or MitoTEMPO (mitochondria-targeted antioxidant) were studied. Blood pressure and echocardiography were noninvasively evaluated, followed by ex vivo assessments of isolated heart and diaphragm muscle functions. Treatment with L-NIO attenuated the T4-induced hypertension in mice. However, apocynin improved the left-ventricular (LV) dysfunction without preventing the cardiac hypertrophy in these mice. Both allopurinol and MitoTEMPO reduced the T4-induced fatiga...Continue Reading

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Citations

Jul 7, 2015·Oxidative Medicine and Cellular Longevity·Mohammad T ElnakishPaul M L Janssen
Mar 13, 2019·Expert Opinion on Drug Discovery·Paul M L Janssen, Mohammad T Elnakish
Jun 19, 2018·Frontiers in Physiology·Flavia F BloiseTania M Ortiga-Carvalho
Jul 17, 2018·Journal of Neuromuscular Diseases·Jeovanna LowePaul M L Janssen
Jan 17, 2020·Aging Medicine·Ben KirkGustavo Duque
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Nov 8, 2017·Journal of Cardiovascular Pharmacology·Steven J RepasMohammad T Elnakish
Nov 11, 2020·Proceedings. Biological Sciences·Alejandro CantareroCarlos Alonso-Alvarez

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