N-Acetylcysteine, an ROS Inhibitor, Alleviates the Pathophysiology of Hyperthyroidism-Induced Cardiomyopathy via the ROS/Ca2+ Pathway

Abstract

Hyperthyroidism is common and can induce cardiomyopathy, but there is no effective therapeutic strategy. The purpose of this study was to investigate the molecular mechanism of hyperthyroidism-induced cardiomyopathy (HTC) and the effect of N-acetylcysteine (NAC), an ROS inhibitor, on the pathophysiology of HTC in vivo and in vitro. Compared with those in the control groups in vivo and in vitro, TT3 and TT4 were significantly increased, the structure of myocardial cells was enlarged and disordered, and interstitial fibrosis and the apoptosis of myocardial cells were markedly increased in the L-Thy group. The ROS and inflammatory response were increased in the hyperthyroidism group. In the NAC group, the contents of TT3 and TT4 were decreased, the myocardial cell structure was slightly disturbed, fibrosis and apoptosis were significantly reduced, and the ROS level and inflammatory response were significantly reduced. Interestingly, L-Thy decreased the viability of fibroblasts and H9c2 cells, suggesting that L-Thy-induced fibrosis was not caused by the proliferation of fibroblasts. The molecular mechanism of HTC could be explained by the fact that L-Thy could cause cardiac hypertrophy, inflammation, and fibrosis by regulating the Ca2+/calpain/Rcan1-dependent signalling pathway, the Ca2+/Rcan1/NF-κB/p65-dependent signalling pathway, and the Ca2+/ROS/Bcl-2/caspase-3-dependent signalling pathway. In conclusion, NAC can alleviate the pathophysiology of hyperthyroidism-induced cardiomyopathy, probably by regulating the ROS/Ca2+-dependent pathway.

Effects of gas signaling molecule SO2 in cardiac functions of hyperthyroid rats

“…The Masson staining and Western-Blot results revealed that myocardial collagen synthesis was significantly increased in hyperthyroid rats, accompanied by impaired synthesis and clearance of extracellular matrix and obviously increased myocardial fibrosis. Similarly, Bao et al [29] reported a significant increase in interstitial fibrosis in cardiac myocytes of hyperthyroid rats, which is accompanied by weakened cardiac function and cardiac hypertrophy. In addition, Khamis et al [34] found significant upregulations of cardiac fibrosis-related genes of SMAD-2, SMAD-3, SMAD-4, TGF-β, and NF-κβ in myocardial tissues of hyperthyroid rats, and severely disturbed fibrotic changes in myocardial histopathology.…”

“…Similarly, Bao et al . [ 29 ] reported a significant increase in interstitial fibrosis in cardiac myocytes of hyperthyroid rats, which is accompanied by weakened cardiac function and cardiac hypertrophy. In addition, Khamis et al .…”

“…The cells were divided into a control group, a L-Thy group, a L-Thy + SO 2 group, a L-Thy + SO 2 + HDX group, and a SO 2 group according to different treatments. The cells in the control group and the SO 2 group were cultured with a normal medium, and those in the L-Thy group and L-Thy + SO 2 group were treated with 2 μM L-Thy at 37°C for 24 h [ 29 ]. The cells in the L-Thy + SO 2 and L-Thy + SO 2 + HDX groups were pretreated for 0.5 h by adding exogenous SO 2 donor Na 2 SO 3 /NaHSO 3 (100 μM, 3:1 mol rate), as described previously [ 30 ].…”

The ROS mediates MCUb in mitochondria-regulated apoptosis of TM4 cells induced by titanium dioxide nanoparticles

“…However, the exact molecular mechanisms underlying this process remains unknown. It has been proposed that the intracellular ROS may disrupt in disrupt Ca 2 + homeostasis and inducing the cell apoptosis [26,27]. MCUb had been eluciated as a key regulator, exerting structural and physiological inhibitory of mitochondrial calcium exchange [28].…”