ABSTRACT
The aim of this study was to investigate the effects of melatonin on the serum asymmetric dimethylarginine (ADMA) levels and the expressions of vaspin, visfatin, dimethylarginine dimethylaminohydrolase (DDAH), and signal transducer and activator of transcription-3 (STAT-3) for evaluation of endothelial function and inflammation in the hypercholesterolemic rats. Rats were divided into 5 groups: (1) control, (2) hypercholesterolaemia, (3) melatonin administrated concurrently with cholesterol diet, (4) melatonin administrated only last 2 weeks and fed with cholesterol diet, (5) atorvastatin administered only last 2 weeks fed with cholesterol diet. Although an increase was observed in the expressions of visfatin and STAT-3 and the serum ADMA levels, the vaspin and DDAH protein expressions were found to decrease with hypercholesterolemic diets. Melatonin was determined to restore all the parameters to the normal levels. In conclusion, melatonin may have protective and therapeutic effects on hypercholesterolaemia by regulating vaspin, STAT-3, DDAH, and ADMA signalling pathways and create similar effects with atorvastatin.
Subject(s)
Atherosclerosis , Hypercholesterolemia , Hyperlipidemias , Melatonin , Rats , Animals , Melatonin/pharmacology , Melatonin/therapeutic use , Nicotinamide Phosphoribosyltransferase , Hypercholesterolemia/complications , Hypercholesterolemia/drug therapy , Atorvastatin/pharmacology , Atorvastatin/therapeutic use , Inflammation/drug therapy , Atherosclerosis/drug therapy , Atherosclerosis/etiology , Nitric Oxide/metabolismABSTRACT
BACKGROUND AND AIM OF THE STUDY: Ischemic postconditioning (PostC) is considered to be one of the strongest mechanisms limiting the extent of myocardial infarction, and reducing ischemia-reperfusion (I/R) injury. I/R-induced myocardial injury results in apoptosis, autophagy, and necrosis. The aim of the present study was to investigate the roles of the necrotic gene cytochrome b-245 beta chain (Cybb); Cybb-related microRNA miR139-3p; the autophagy gene Beclin-1 (Becn1); proapoptotic genes Fas, Faslg and growth arrest and DNA-damage-inducible 45 alpha (Gadd45a); and apoptosis-related microRNA miR181a-1 levels on I/R injury, as well as, the potential protective effects of PostC through this gene and microRNAs. METHODS: The left main coronary artery was subjected to ischemia for 30 minutes, followed by reperfusion for 120 minutes. PostC involved three cycles of I/R, each lasting 10 seconds. Gene and microRNA levels were analyzed using a quantitative reverse transcription-polymerase chain reaction. RESULTS: Although an increase was observed in the expression levels of the Cybb, Fas, Faslg and Gadd45a genes, the miR139-3p, miR181a-1, and Becn1 expression levels were found to decrease with I/R injury. PostC was determined to restore the expression of all the genes to the normal levels. CONCLUSIONS: The abovementioned genes can be used as important prognostic markers in the diagnosis of reperfusion injury and in the evaluation of treatment efficacy. It was further noted that increased expression of CYBB, which is one of the target genes for miR139-3p, and a decreased expression of miR181a-1 may cause apoptosis by affecting Fas and Faslg signaling. PostC can inhibit apoptosis by increasing miR139-3p and miR181a-1 levels.
Subject(s)
Apoptosis/genetics , Coronary Vessels , Fas Ligand Protein/genetics , Fas Ligand Protein/metabolism , Ischemic Postconditioning , MicroRNAs/genetics , MicroRNAs/metabolism , Myocardial Infarction/genetics , Myocardial Reperfusion Injury/genetics , NADPH Oxidase 2/genetics , NADPH Oxidase 2/physiology , Proteins/genetics , Proteins/metabolism , Signal Transduction/physiology , fas Receptor/genetics , fas Receptor/metabolism , Coronary Vessels/metabolism , Gene Expression , Humans , Prognosis , Signal Transduction/geneticsABSTRACT
OBJECTIVE: Protective effects of ischemic postconditioning (PostC) decrease/disappear with age and chronic heart diseases. Similarly, low serum melatonin levels have been reported in the same risk groups. The aims of this study were to investigate the effects of melatonin on the protection of PostC in ischemia-reperfusion (I/R)-induced infarct size and roles of uncoupling protein (UCP) 3, irisin, and nuclear factor kappa B (NFkB) levels. METHODS: Rats were pinealectomized (Px) or sham operated (non-Px) 2 months before the I/R studies. The left main coronary artery was occluded for 30 min followed by 120 min reperfusion. PostC was induced with three cycles of R/I (10 s each) after ischemia. RESULTS: The infarct size was found to be significantly higher in Px rats (54.68±1.5%) than in the control group (35.1±2.5%). PostC and melatonin administrations to non-Px rats significantly reduced the infarct size. On the other hand, PostC did not create a significant effect in Px rats, but protection was provided when PostC was co-administrated with melatonin. While significant decreases were detected in the UCP3 levels, irisin and NFkB levels increased with I/R and Px. Treatment with PostC and melatonin in non-Px groups and their co-administration in Px groups were found to return all the genes close to normal levels. CONCLUSION: The physiological and pharmacological concentrations of melatonin may play a role in the protection of PostC. In cases when physiological melatonin is reduced, such as aging and heart diseases, this protection may decrease, and this effect may be restored by melatonin replacement. PostC and melatonin may regulate energy metabolism and inflammatory mediators and protect mitochondria by affecting the UCP3, irisin, and NFkB levels.
