Abstract
BackgroundHyperthyroidism is known to increase the risk of ischemic heart diseases. Octreotide has been reported to attenuate ischemia/reperfusion (I/R) injury. Whether it is useful when ischemic heart disease is accompanied with co-morbidities like hyperthyroidism needs more clarifying. So, this study aimed to explore the effect of octreotide on cardiac I/R injury in hyperthyroid rats and to clarify if Nrf2 activation is involved in this effect. Forty adult female Wistar rats were subdivided into control (euthyroid) (n = 10) and hyperthyroid (n = 30) groups. Rats in hyperthyroid group received l-thyroxine (12 mg/L) in drinking water for 35 days, then were randomly divided into three equal subgroups (n = 10): hyperthyroid control positive group, hyperthyroid octreotide treated group, and hyperthyroid octreotide + Nrf2 inhibitor (brusatol) treated group. Isolated hearts were submitted to I/R and evaluated for cardiac hemodynamics and infarct size. Serum T3 and T4, coronary efflux lactate dehydrogenase (LDH) and creatine kinase-myoglobin binding (CK-MB) and cardiac tissue malondialdehyde (MDA) were estimated. Nrf2- regulated gene expressions of HO-1, SOD, GPx, and catalase were assessed.ResultsOctreotide administration to hyperthyroid rats improved baseline and post-ischemic recovery of cardiac hemodynamics, decreased the high coronary efflux LDH and CK-MB and tissue MDA, reduced infarction size, and upregulated the decreased antioxidative enzymes HO-1, SOD, GPx, and catalase mRNA expressions in the hyperthyroid I/R rat hearts. The Nrf2 inhibitor brusatol reversed the cardioprotective effect of octreotide in hyperthyroid I/R rat hearts.ConclusionOctreotide can reduce oxidative stress to effectively alleviate I/R injury in the hyperthyroid rat hearts through upregulation of Nrf2-dependent antioxidative signaling pathways.
Highlights
Hyperthyroidism is known to increase the risk of ischemic heart diseases
Reperfusion effectively reduces the mortality of cardiac cells, early restoration of blood flow leads to overproduction of free radicals like reactive oxygen species (ROS), which may further lead to cardiac tissue injury [3] accompanied by activation of cardioprotective mechanisms, an effect called hormesis [4]
The current study aimed to explore the effect of octreotide on cardiac I/R injury in hyperthyroid female rats and to clarify if Nrf2 activation is involved in this effect
Summary
Hyperthyroidism is known to increase the risk of ischemic heart diseases. Octreotide has been reported to attenuate ischemia/reperfusion (I/R) injury. Reperfusion effectively reduces the mortality of cardiac cells, early restoration of blood flow leads to overproduction of free radicals like reactive oxygen species (ROS), which may further lead to cardiac tissue injury [3] accompanied by activation of cardioprotective mechanisms, an effect called hormesis [4]. These mechanisms include production of important antioxidative molecules as catalase, superoxide dismutases (SOD), glutathione, glutathione S-transferases, glutathione peroxidases (GPx), heme oxygenases (HO), thioredoxin reductases, and thioredoxins that can be regulated by the transcription factor nuclear factor (erythroid 2-related) factor 2 (Nrf2) [5]. Activation of Nrf could be considered as a therapeutic option in cardiovascular diseases [7]
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