Melatonin protects against oxidative damage and restores expression of GLUT4 gene in the hyperthyroid rat heart

Abstract

To understand the mechanism of cardiovascular dysfunction in the hyperthyroid condition, the role of oxidative stress was examined in rats treated with 3,5,3'-triiodo-l-thyronine (T3). Treatment of rats daily with T3 (8 microg/100 g BW) for 15 days resulted in an increase in heart weight to body weight ratio, which was ameliorated by antioxidants, melatonin (2 mg/100 g BW) or vitamin E (4 mg/100 g BW). Both melatonin and vitamin E also inhibited rises of lipid peroxidation and hydroxyl radical generation and prevented the inhibition of Cu,Zn-superoxide dismutase in the hypertrophic heart. The expression of the glucose transporter, GLUT4, was reduced in response to T3, which was completely restored by melatonin and partially by vitamin E. However, neither antioxidant prevented down regulation of peroxisome proliferator-activated receptor-alpha in the hyperthyroid heart. Furthermore, the reduced level of myocyte enhancer factor-2, a regulator of GLUT4 transcription was restored completely by melatonin and partially by vitamin E treatment. Glucose uptake in hypertrophic left ventricular cells was also restored by these antioxidants. The expression of B-type natriuretic peptide, a marker of heart failure, was significantly increased by T3 and ameliorated by melatonin or vitamin E treatments. In general, the beneficial effects of melatonin given as a co-treatment with T3 were better than those induced by vitamin E. These data show that melatonin ameliorates hypertrophic growth of the myocardium induced by hyperthyroidism and provide an insight into the mechanism of reactive oxygen species-mediated down regulation of metabolically important genes such as GLUT4 in the heart.

Melatonin prevents fibrosis but not hypertrophy development in the left ventricle of NG-nitro-L-arginine-methyl ester hypertensive rats

“…Although melatonin was suggested to have some antiremodelling potential [6] and was shown to prevent cardiac hypertrophy, to reduce oxidative load and to alter the expression of metabolically important genes in the hyperthyroid rat [23], in our study melatonin failed to prevent LVH induced by L-NAME. Some studies have suggested that NO delivery might attenuate LVH independently of blood pressure reduction [24], whereas others have indicated that the haemodynamic load may be the major determinant of LVH, and neurohumoral activation including NO may play a rather modulatory role [13,25].…”

Hyperthyroidism causes cardiac dysfunction by mitochondrial impairment and energy depletion

“…Excess T 3 induces a hypermetabolic state in the heart and also increases cellular respiration leading to increased ROS production, which is not completely neutralized by the cellular antioxidants, and there is gradual and progressive accumulation of ROS in cardiomyocytes (Ghosh et al 2007, Abel & Doenst 2011. This is evident from increased lipid peroxidation and depletion of cellular antioxidants seen after 15 days of T 3 treatment ( Fig.…”

“…Lipid peroxides in the cell-free homogenate obtained from LV tissue were determined as described earlier (Ghosh et al 2007). Briefly, LV tissue (200 mg) was homogenized in ice-cold 0.9% saline (pH 7.0) with a Potter-Elvehjem glass homogenizer for 30 s. The homogenate was centrifuged at 800 g for 3 min at 4 8C and the cell-free homogenate was mixed with thiobarbituric acid (TBA)-trichloro acetic acid reagent with thorough shaking.…”

Excess of Glucocorticoid Induces Cardiac Dysfunction via Activating Angiotensin II Pathway

“…The lipid peroxides in the homogenate was determined as thiobarbituric acid reactive substances (TBARS) by previously described method [33,34]. Briefly, the homogenate was mixed with TBA-TCA (Thiobarbituric acidTrichloro acetic acid) reagent with thorough shaking and boiled for 15 min in a boiling water bath.…”