N-Acetylcysteine Prevents Low T3 Syndrome and Attenuates Cardiac Dysfunction in a Male Rat Model of Myocardial Infarction

Abstract

Nonthyroidal illness syndrome (NTIS) affects patients with myocardial infarction (MI). Oxidative stress has been implicated as a causative factor of NTIS, and reversed via N-acetylcysteine (NAC). Male Wistar rats submitted to left anterior coronary artery occlusion received NAC or placebo. Decreases in triiodothyronine (T3) levels were noted in MI-placebo at 10 and 28 days post-MI, but not in MI-NAC. Groups exhibited similar infarct areas whereas MI-NAC exhibited higher ejection fraction than did MI-placebo. Left ventricular systolic and diastolic diameters were also preserved in MI-NAC, but not in MI-placebo. Ejection fraction was positively correlated with T3 levels. Oxidative balance was deranged only in MI-placebo animals. Increased type 3 iodothyronine deiodinase expression was detected in the cardiomyocytes of MI-placebo compared with normal heart tissue. NAC was shown to diminish type 3 iodothyronine deiodinase expression and activity in MI-NAC. These results show that restoring redox balance by NAC treatment prevents NTIS- related thyroid hormone derangement and preserves heart function in rats subjected to MI.

Short-term exercise training improves cardiac function associated to a better antioxidant response and lower type 3 iodothyronine deiodinase activity after myocardial infarction

“…This is confirmed by the positive correlation of D3 with carbonyls and the negative correlation with TRx (Fig 5). These findings are in line with other studies, that demonstrated increased antioxidant defenses after MI in the presence of antioxidant medication, rebalancing the redox status, preventing changes in thyroid metabolism and improving cardiac function [3].…”

“…These series of parameters is consistent with that assessed in other studies by our research group [6, 8, 16] and others as well [26, 27]. In addition, the reduction in cardiac function may be largely explained by increased protein oxidation (augmented carbonyl levels) and D3 activity in cardiac tissue sample of the infarcted animals [3]. With regard to hemodynamic parameters, SBP increased regardless of the animals’ status (acute MI or sham) showing that, in this experimental model, acute MI did not induce any hemodynamic changes.…”

“…An increase in D3 was shown in a rat model of right ventricular hypertrophy due to pressure overload [2]. We also have found increased D3 activity after MI associated to imbalance in the redox state (pro-oxidative) [3]. MI-induced increase in D3 activity was associated with lower T3 concentration in cardiomyocytes, whereas plasma T3 levels were unchanged [4].…”

Correlation of Triiodothyronine Level with In-Hospital Cardiac Function and Long-Term Prognosis in Patients with Acute Myocardial Infarction

“…While T4 is solely a product of the thyroid gland, T3 is a product of the thyroid and of many other tissues. Low T3 level has been proven to be correlated with myocardial damage in animal models [12] and is associated with a poor cardiovascular prognosis in human [11, 13, 14]. Previous studies have indicated that subclinical hypothyroidism could be a predictor of adverse cardiovascular outcomes in patients with acute decompensated heart failure [14–16], and low T3 has been correlated with worse hospital outcomes in patients with acute HF [11, 14].…”

Current concepts and challenges to unravel the role of iodothyronine deiodinases in human neoplasias

“…Importantly, DIO3 is reexpressed in normal and pathological hyperproliferative conditions. DIO3 reactivation has been demonstrated in the pathological context of cardiac hypertrophy, myocardial infarction, critical illness and several types of cancer (Huang 2005, Lehnen et al 2017.…”