title: Selenium downregulates oxidative stress-induced activation of leukotriene pathway in experimental rats with diabetic cardiac hypertrophy.
abstract: Cardiac hypertrophy has been considered as an important risk factor of morbidity and mortality. It is characterized as thickening of ventricle wall of the heart and consequent reduction in the contracting ability of the heart to pump the blood. Hyperglycemia-induced reactive oxygen species act as major mediators of diabetic complications. Inflammation plays an essential role in the development of diabetic cardiac hypertrophy. Selenium has been shown to induce insulin-like and anti-inflammatory effects in human and experimental animals. But, its mechanism of action has not been elucidated. Hence, in order to probe into its mechanism at molecular level, we designed an experiment to study the effect of selenium as sodium selenite in streptozotocin-induced diabetic rats. The rats were divided into four groups and maintained as follows: (1) controls, (2) sodium selenite-treated controls, (3) diabetic, and (4) sodium selenite-treated diabetic rats. Duration of the experiment was 30 days. Selenium supplementation enhanced the streptozotocin-induced reduction in the activities of antioxidant enzymes, decreased the serum glucose level, glycated hemoglobin content, concentration of high-sensitivity C-reactive protein, levels of lipid peroxidation products, as well as inflammatory parameters. Decrease in the phospholipase activity by selenium supplementation also contributed to the downregulation of leukotriene pathway. It also downregulated the expressions of nuclear transcription factor κB (NFκB), lipoxygenase, cyclooxygenase, 5-lipoxygenase-activating protein, and receptor for leukotriene B4. Hence, selenium decreased the production of reactive oxygen species and inhibited the activation of NFκB-mediated transcription of pro-inflammatory mediators which resulted in the downregulation of leukotriene pathway in diabetic cardiac hypertrophy.
authors: Department of Biochemistry, University of Kerala, Kariavattom, Thiruvananthapuram, 695581, Kerala, India.
authors: B L
authors: BL
authors: Dhanya
authors: R P
authors: RP
authors: Swathy
authors: M
authors: M
authors: Indira
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D058065:Diabetic Cardiomyopathies / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D015536:Down-Regulation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006442:Glycated Hemoglobin / Q000378:metabolism; D015289:Leukotrienes / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D018038:Sodium Selenite / Q000008:administration & dosage / Q000494:pharmacology*; D014131:Trace Elements / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D001094:Arachidonate 5-Lipoxygenase; D001786:Blood Glucose; D002097:C-Reactive Protein; D051546:Cyclooxygenase 2; D006442:Glycated Hemoglobin; D015289:Leukotrienes; D016328:NF-kappa B; D018038:Sodium Selenite; D014131:Trace Elements