Effects of Gap 26, a Connexin 43 Inhibitor, on Cirrhotic Cardiomyopathy in Rats.

Introduction Cirrhotic cardiomyopathy (CCM) is recognized by impaired cardiac responsiveness to stress, prolonged QT interval, and systolic and diastolic dysfunctions. Connexins are a family of transmembrane proteins that play a key role in cardiac physiology. Connexin 43 (Cx43) inhibition showed cardio-protective effects.

Evaluation of statins as a new therapy to alleviate chronotropic dysfunction in cirrhotic rats.

Aims: Liver cirrhosis defines by regenerative nodules and fibrotic septa, causing a complication called cirrhotic cardiomyopathy (CCM) with chronotropic hypo-responsiveness. In addition to lowering cholesterol levels, statins yield antioxidant and anti-inflammatory effects. In liver diseases animal models, statins have been shown to decrease hepatic inflammation, fibrogenesis, and portal pressure (PP).

Current Models for Predicting Drug-induced Cholestasis: The Role of Hepatobiliary Transport System.

Drug-induced cholestasis is the main type of liver disorder accompanied by high morbidity and mortality. Evidence for the role of hepatobiliary pumps in the cholestasis patho-mechanism is constantly increasing. Recognition of the interactions of chemical agents with these transporters at the initial phases of drug discovery can help develop new drug candidates with low cholestasis potential.

Evaluation of the effect of heat shock protein 70 targeted drugs on cirrhotic cardiomyopathy in biliary cirrhotic rats.

Aims: Liver cirrhosis leads to cirrhotic cardiomyopathy (CCM) and chronotropic incompetence (CI). Heat shock protein 70 (Hsp70) regulates cellular apoptosis and autophagy in stress. Teprenone modulates the Hsp70 and protects against cellular injury.

Effect of phosphatidylserine on cirrhosis-induced hepatic encephalopathy: Response to acute endotoxemia in cirrhotic rats.

Background/aims: In cirrhosis, the levels of proinflammatory cytokines are high in the liver and blood. Endotoxin decreases level of consciousness in cirrhotic rats. Phosphatidylserine exists in the cell membrane structure and is essential for the survival of neurons.

Thalidomide attenuates the hyporesponsiveness of isolated atria to chronotropic stimulation in BDL rats: The involvement of TNF-α, IL-6 inhibition, and SOCS1 activation.

Objectives: Cirrhotic cardiomyopathy is a complication of uncured cirrhosis which is associated with hyporesponsiveness of the heart to sympathetic stimulation. The enhancement of portal pressure, nitric oxide (NO) level, pro-inflammatory mediators and down-regulation of Suppressor of Cytokine Signaling 1 (SOCS1) are involved in this situations. The present study seeks to examine the beneficial effect of thalidomide on cirrhotic cardiomyopathy.

Sumatriptan Increases Skin Flap Survival through Activation of 5-Hydroxytryptamine 1b/1d Receptors in Rats: The Mediating Role of the Nitric Oxide Pathway.

Background: Random pattern skin flaps are applicable for reconstructing any defect in plastic surgery. However, they are difficult to apply because of necrosis. Sumatriptan, a selective 5-hydroxytryptamine 1b/1d agonist, is routinely used to offset acute migraine attacks.

Evaluation of Isolated Vascular Response to 5HT1A, 5HT1B1D & 5HT2A Receptors Agonist & Antagonist in Chronic Endotoxemic Rats.

The main vascular feature in endotoxemia is impaired contractile responses to vasoactive agents. We study the aortic response to 5HT11 A, 5HT1B1D and 5HT2A receptors agonist and antagonist in chronic endotoxemic rats. Intraperitoneal injection of 1 mg/kg lipopolysaccharide for 5 days induced chronic endotoxemia.

Cardiac chronotropic hypo-responsiveness and atrial fibrosis in rats chronically treated with lithium.

Lithium is a widely used mood-stabilizing agent; however, it causes a variety of cardiovascular side effects including sinus node dysfunction. In this study we explored the potential adverse effects of lithium on cardiac chronotropic responsiveness, atrial tissue histology and gene expression in rats that were chronically treated with therapeutic doses of lithium. Male Wistar albino rats were given lithium chloride (2.

Protective effects of magnesium sulfate against doxorubicin induced cardiotoxicity in rats.

Aims: Clinical use of doxorubicin, an effective chemotherapeutic agent, has limited uses due to dose-dependent cardiac toxicity. It has been supposed that the production of free radicals and calcium ions overload can lead to cardiac toxicity. Magnesium is a cardioprotective drug which inhibits lipid peroxidation and reducing myocardial apoptosis.

Evaluation of Chronic Losartan Treatment Effect on Cardiac Chronotropic Dysfunction in Biliary Cirrhotic Rats.

Cirrhosis is associated with cardiac chronotropic and inotropic dysfunction which is known as cirrhotic cardiomyopathy. Cardiac responsiveness to adrenergic stimulation is impaired in cirrhosis. Moreover, there is vagal nerve dysfunction which is related to neuromodulatory dysfunction of the angiotensin II in the cirrhosis.

Pharmacological evidence for the involvement of the NMDA receptor and nitric oxide pathway in the antidepressant-like effect of lamotrigine in the mouse forced swimming test.

Lamotrigine is an anticonvulsant agent that shows clinical antidepressant properties. The aim of the present study was to investigate the involvement of N-methyl-d-aspartate (NMDA) receptors and nitric oxide-cyclic guanosine monophosphate (NO-cGMP) synthesis in possible antidepressant-like effect of lamotrigine in forced swimming test (FST) in mice. Intraperitoneal administration of lamotrigine (10mg/kg) decreased the immobility time in the FST (P<0.

Involvement of NMDA receptors and L-arginine/nitric oxide/cyclic guanosine monophosphate pathway in the antidepressant-like effects of topiramate in mice forced swimming test.

Topiramate (TPM) is an agent primarily used in the treatment of epilepsy. Using mice model of forced swimming test (FST) the current study was basically aimed to investigate the influence of TPM on depression by inhibiting NMDA receptor and nitric oxide-cGMP production. When TPM was administered in a dose of 20 and 30 mg/kg by i.

Involvement of Inflammatory Cytokines in Antiarrhythmic Effects of Clofibrate in Ouabain-Induced Arrhythmia in Isolated Rat Atria.

Considering the cardioprotective and anti-inflammatory properties of clofibrate, the aim of the present experiment was to investigate the involvement of local and systemic inflammatory cytokines in possible antiarrhythmic effects of clofibrate in ouabain-induced arrhythmia in rats. Rats were orally treated with clofibrate (300 mg/kg), and ouabain (0.56 mg/kg) was administered to animals intraperitoneally.

Cirrhosis-induced morphological changes in the retina: possible role of endogenous opioid.

Aim: To investigate the impact of cirrhosis on retinal morphology and to evaluate the role of endogenous opioids as a mediator in cirrhosis induced retinal change.

Methods: Thirty-six male rats were divided into 3 main groups; the common bile duct ligated (BDL) group, the sham-operated (Sham) group and the unoperated (Unop) group. Then each of these three main groups was divided into two subgroups; the first subgroup received daily injection of naltrexone hydrochloride (NTX) and the second group was injected with normal saline (Saline) daily.

Mesenteric artery responsiveness to acetylcholine and phenylephrine in cirrhotic rats challenged with endotoxin: the role of TLR4.

Cirrhosis is associated with vascular dysfunction and endotoxemia. These experiments were designed to investigate the hypothesis that the administration of a low-dose of lipopolysaccharide (LPS) worsens vascular dysfunction in rats subjected to bile-duct ligation (BDL), and to determine whether LPS initiates changes in vascular Toll-like receptor 4 (TLR4) expression. Four weeks after BDL, the animals were given an intraperitoneal injection of either saline or LPS (1.

Prostaglandin F₂α modulates atrial chronotropic hyporesponsiveness to cholinergic stimulation in endotoxemic rats.

Endotoxemia induces various physiological adaptive responses such as tachycardia. There is evidence to show that inflammatory tachycardia might be linked to a direct action of prostanoids on the cardiac pacemaker cells. Recent reports have indicated that systemic inflammation may uncouple of cardiac pacemaker from cholinergic neural control in experimental animals; however, the exact mechanism of this phenomenon is uncertain.

Effects of D-penicillamine on pentylenetetrazole-induced seizures in mice: involvement of nitric oxide/NMDA pathways.

Besides the clinical applications of penicillamine, some reports show that use of D-penicillamine (D-pen) has been associated with adverse effects such as seizures. So, the purpose of this study was to evaluate the effects of D-pen on pentylenetetrazole (PTZ)-induced seizures in male NMRI mice. It also examined whether N-methyl-D-aspartate (NMDA) receptor/nitrergic system blockage was able to alter the probable effects of D-pen.

Teratogenic effects of coadministration of fluoxetine and olanzapine on rat fetuses.

Objective. Depression during pregnancy is a relatively common problem. Since little is known about the teratogenic effects of concomitant administration of fluoxetine and olanzapine during the organogenesis period, the aim of the present study was to evaluate the teratogenic effects of coadministration of fluoxetine and olanzapine on rat fetuses.

Effect of endotoxin on heart rate dynamics in rats with cirrhosis.

Reduced heart rate variability (HRV) is a hallmark of systemic inflammation which carries negative prognostic information in sepsis. Decreased HRV is associated with partial uncoupling of cardiac pacemaker from cholinergic neural control during systemic inflammation. Sepsis is a common complication in liver cirrhosis with high mortality.

Cirrhosis is associated with development of tolerance to cardiac chronotropic effect of endotoxin in rats.

Background/aims: Sepsis is a common complication of cirrhosis with a high mortality. Cirrhosis is associated with cardiac chronotropic and inotropic dysfunction, which is known as cirrhotic cardiomyopathy and might be linked to endotoxaemia. This study was aimed to explore the hypothesis that the inflammatory response induced by administration of low dose of lipopolysaccharide (LPS) exacerbates cardiac chronotropic dysfunction in cirrhotic rats; and if so, whether this is associated with altered cardiac toll-like receptor expression.