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Cirrhotic cardiomyopathy is a well-recognized cardiac dysfunction in cirrhotic patients. Studies have confirmed the protective effects of silymarin in different types of cardiac injury. This study aimed to examine the effectiveness and molecular mechanism of silymarin against myocardial dysfunction and hypertrophy in a rat model of cirrhosis.The experiment was performed at Alborz University of Medical Sciences (Karaj, Iran) during 2020-2021. Thirty-two male Wistar rats were randomly divided into four groups of Sham-operated (control group for surgical procedures), Bile Duct Ligated (BDL), and two Silymarin extract (SE)-treated groups of 300 and 600 mg/Kg/day. After 28 days, serum levels of AST, ALT, GGT, and ALP, liver histopathological status, as well as cardiac mechanical function, were assessed. Cardiac βBDL was associated with a significant elevation in serum AST, ALT, GGT, and ALP, development of necrosis and fibrosis of the liver texture, increased Heart Weight and Heart Weight to Body Weight ratio, enhanced cardiac mechanical function as well as a significant up-regulation of ventricular βSilymarin treatment in higher dose attenuated cirrhosis-associated cardiac remodeling and reduced cardiac mechanical dysfunctions.

Previous studies show that anabolic steroids impair innate cardioprotective mechanisms. Here, we investigated the effect of supraphysiological doses of nandrolone on ischemic preconditioning (IPC) as a potent cardioprotective tool against ischemia reperfusion (IR) injury in rat hearts. Male Wistar rats in two experimental settings of sedentary and exercise-trained (60 min/day swimming, 5 days/week, for 8 weeks) were either pretreated with intramuscular injections of arachis oil (Arach, n = 16) as vehicle or nandrolone decanoate (ND, n = 8), 10 mg/kg/week, for 8 weeks. At the end, the hearts were excised and perfused in a Langendorff system. Then, the vehicle-treated hearts subdivided into the IR (30 min of LAD coronary artery occlusion and 120 min reperfusion, n = 8) and IPC (three cycles of 3-min ischemia and 3-min reperfusion before test ischemia, n = 8) groups and nandrolone-treated hearts served as ND + IPC (nandrolone pretreatment before IR and IPC protocols, n = 8) group. Post-ischemic cardiac function and infarct size were assessed. Reperfusion arrhythmias were analyzed using a standard scoring system. In sedentary hearts, ND slightly increased heart-to-body weight ratio and increased baseline cardiac contractile function. In trained hearts, ND markedly increased heart-to-body weight ratio which was also associated with enhanced baseline cardiac function. ND pretreatment enhanced protective effects of IPC in sedentary group; however, abolished these effects in exercise-trained group. The arrhythmia score was not significantly different between nandrolone-treated groups vs. respective preconditioned groups. Our findings show that ND impairs IPC-induced cardioprotection in exercise-trained rat hearts. Cardiac hypertrophy seems to play a crucial role in this response.

The current study examines the protective effect of oxytocin (OT) on cardiomyocyte apoptosis modulated by mitochondrial ATP-dependent potassium (mitoKATP) channel and permeability transition pore (mPTP) in the preconditioned myocardium of anesthetized rats. Eighty rats were equally divided into eight groups. The hearts of all animals except for the sham group were subjected to 25 min ischemia and 120 min reperfusion. Oxytocin, 5-hydroxydeconoate (5-HD), a specific inhibitor of the mitoKATP channel, and atractyloside (ATRC), an mPTP opener, were used prior to ischemia. Hemodynamic parameters were recorded throughout the experiment. Evaluations were made by infarct size, plasma lactate dehydrogenase level (LDH), transmission electron microscopy (TEM) and immunohistochemistry studies. OT prevented mean arterial pressure drop during early phase of ischemia and reperfusion. Treatment with OT before IR induction normalizes cardiomyocytes both in light microscopy and TEM observations. In addition, OT significantly reduced TUNEL- and increased Bcl-2-labeled positive cell number relative to IR (p

Recent studies suggest that intermittent and prolonged normobaric hyperoxia (HO) results in ischemic tolerance to reduce ischemic brain injury. In this research, we attempted to see changes in excitatory amino acid transporters (EAATs) and TNF-alpha levels following prolonged and intermittent hyperoxia preconditioning. Rats were divided into four experimental groups, each of 21 animals. The first two were exposed to 95% inspired HO for 4 h/day for 6 consecutive days (intermittent HO, InHO) or for 24 continuous hours (prolonged HO, PrHO). The second two groups acted as controls, and were exposed to 21% oxygen in the same chamber. Each main group was subdivided to middle cerebral artery occlusion (MCAO-operated), sham-operated (without MCAO), and intact (without any surgery) subgroups. After 24 h from pretreatment, MCAO-operated subgroups were subjected to 60 min of right MCAO. After 24 h reperfusion, neurologic deficit score (NDS) and infarct volume were measured in MCAO-operated subgroups. EAATs expression and serum TNF-alpha levels were assessed in sham-operated and intact subgroups. Preconditioning with prolonged and intermittent HO decreased NDS and upregulated EAAT1, EAAT2, and EAAT3 and increased serum TNF-alpha levels significantly. Although further studies are needed to clarify the mechanisms of ischemic tolerance, the intermittent and prolonged HO seems to partly exert their effects via increase serum TNF-alpha levels and upregulation of EAATs.

Abnormalities of the modulatory roles played by the endothelium and/or smooth muscle may be critical and initiating factors in the development of diabetic vascular disease. Decreased phosphatidylinositol 3-kinase (PI3-K)/Akt pathway activity and impaired nitric oxide production through this pathway may play pivotal roles in the diabetes-induced vascular dysfunction. Several findings have demonstrated that exercise training has therapeutic and protective effects in type 1 diabetes and could correct endothelial dysfunction. The molecular mechanisms, however, are only partially understood.Male Wistar rats (220+/-10 g, N=60) were made diabetic by streptozotocin (60 mg/kg, subcutaneously). After 1 week of diabetes induction, animals were submitted to exercise training for 10 weeks on a treadmill. To characterize cutaneous microvascular responses by laser Doppler flowmetery, animals were deeply anesthetized by intraperitoneal injection of pentobarbital sodium (60 mg/kg) and placed on a heating pad. A rectal thermometer was inserted and body temperature was maintained at 37+/-0.5 degrees C. A tracheotomy was performed to minimize respiratory difficulties. Systemic arterial blood pressure and heart rate were measured by using a tail-cuff during assessment of cutaneous blood flow.(i) Acetylcholine-induced cutaneous perfusion were increased significantly by training in the diabetic groups; (ii) Cutaneous microvascular responses to sodium nitroprusside did not alter in control and diabetic animals by training; and (iii) Local microinjection of insulin increased cutaneous blood flow in trained diabetic and trained control rats compared with age-matched sedentary diabetic and sedentary control normal rats. The administration of wortmannin (PI3K inhibitor) and N-nitro-L-arginine ( nitric oxide synthase inhibitor) before insulin, however, attenuated the increase in cutaneous blood flow in trained diabetic and normal rats.Chronic exercise improved endothelium-dependent dilatation and potentiated insulin vascular function, possibly by PI3-kinase pathway in diabetic rats.

Background Hyperoxic preconditioning is known to protect the heart against necrosis and contractile dysfunction, but protection against arrhythmias has not been well characterized. Objective The authors hypothesized that pre-exposure to normobaric hyperoxia (H) reduces ischemia and reperfusion-induced arrhythmias in isolated rat hearts. Methods Following 60 and 180 min of hyperoxia treatment, rat hearts were isolated immediately (H60 and H180) or 24 h afterward (H60/24 and H180/24), and subjected to 30 min of regional ischemia followed by 120 min of reperfusion. Occurrence, number, and duration of arrhythmias were analyzed during ischemia and reperfusion. In addition, cardiac infarct size was also assessed. Results Sixty and 180 min of breathing hyperoxic gas induced significant protection against severe ischemia and reperfusion-induced arrhythmias. Total number of premature ventricular beats was markedly attenuated by hyperoxia pre-exposure, especially in H60 and H180 groups. Duration of ventricular tachycardia and ventricular fibrillation was also affected by hyperoxia. Hyperoxia reduced the number of ventricular tachycardia episodes in ischemia and reperfusion phase. Accordingly, severity of arrhythmias (arrhythmia score) and infarct size were lower in hyperoxia-treated groups. The effects were more pronounced using hyperoxia immediately before harvesting the heart. Conclusion These results indicate that hyperoxic preconditioning attenuates ventricular ischemia and reperfusion-induced arrhythmias in isolated rat hearts, decreases cardiac infarct size, and improves postischemic heart function. The effects seem to depend on the time course after hyperoxia treatment.