Effect of postconditioning with adenosine on myocardial levels of mitogen activated protein kinase p 38 and serum levels of soluble fas-ligand and cardiac enzymes in rats subjected to intermittent coronary ischemia

Several research works have been done on the last two decades to limit the damaging effect of ischemic episodes of the heart. Brief cycles of coronary artery reperfusion alternating with re-occlusion applied during the first few minutes of reperfusion, reduce irreversible post ischemic injury vice infarct size, endothelial dysfunctions, apoptosis and was termed post conditioning [postC]. It was reported that administration of some potent compounds at the start of reperfusion could protect the heart against injury and one of these is adenosine. The present study was performed to assess the effect of postC with adenosine on the degree of apoptosis among rats subjected to intermittent coronary ischemia. The present study was conducted on 30 male albino rats that were divided into 3 groups [n10]:-Group 1 consisted of normal healthy rats served as control group and they were sham operated. Group2 consisted of rats that undergone coronary ischemia/reperfusion [PR] by3O minutes occlusion of left anterior descending [LAD] artery. Group3 consisted of rats that received adenosine in a dose 200 pg per minute by i.v infusion for 15 minutes after induction of ischemia. Then, postC procedure was done by 3 cycles of 30 seconds reperfusion and 30 seconds re-occlusion of LAD artery that started immediately after the initial reperfusion. The following parameters were estimated in the rats of all groups: myocardial levels of both mitogen activated protein kinase p.38 [MAP kinase p38] and caspase 3 as well as the serum levels of lactate dehydrogenase [LDH], creatine kinase [CK] and soluble Fas-ligand [sFas-L]. The Findings of the present study revealed that exposure of the myocardium to 30 minutes of ischemia followed by 3 hours of reperfusion was associated with increased levels of the markers of myocardial necrosis vice LDH and CK. In addition apoptosis was stimulated as evidenced by increased serum soluble Fas-L and increased myocardial tissue levels of Caspase-3 and the death kinase MAP kinase P38. Treatment of rats in group 3 with adenosine and postC was associated with decreased LDH and CK levels Furthermore, the apoptotic cell loss was also attenuated as evidenced by decreased myocardial caspase-3 and MAP kinase p38 in the treated group. So, postC was reported to delay the wash out of endogenous adenosine and administration of exogenous adenosine was thought to cause myocardial protection by preservation of ATP, improved nucleotide repletion on perfusion, stimulation of glycolysis and limiting myocardial oxygen demand. It was concluded that adenosine and postC technique could be used as an important clinical therapeutic option to attenuate myocardial apoptosis which could decrease the subsequent myocardial dysfunction and heart failure. But further preclinical and clinical studies on human patients are still needed to test this therapeutic approach

possible protective effect of exroxisome proliferator-activated receptors-gamma [PPAR-gamma]-agonist in middle cerebral artery occlusion-induced focal cerebral ischemia in rats

Focal cerebral ischemia [st, oke] is a leading cause of death and disability among adult population. Many pathological events including inflammation and oxidative stress during the acute period contribute to the secondary neuronal death. Peroxisome prohferator-activated receptors [PPARs] are ligand-activated transcription factors known to upstream to many inflammatory and antioxidant genes. The present study was carried out to evaluate the physiological role of PPAR-gamma and possible neuroprotective effects of its agonist, rosiglitazone, in experimentally induced focal cerebral ischemia in rats. The current study was conducted on 30 male albino rats [180-220 gm], they were divided into 3 groups: Group 1: included 10 normal healthy control rats that were sham operated. Group 2: included 10 rats that were subjected to middle cerebral artery occlusion [MCAO] induced focal cerebral ischemia for 2 h followed by reperfusion for 22 h. Group 3: included 10 rats that were pretreated with rosiglitazone 3mg/kg body weight orally for 7 days followed by MCAO induced focal cerebral ischemia. The following parameters were assessed in all rats of the studied groups: Serum levels of both tumor necrosis-alpha [TNF-alpha] and interleukin-6 [IL-6] and cerebral cortex tissue levels of glutathione reductase [GR], reduced glutathi one [GSH] and glutathi one peroxidase [GPx] The present study revealed that the induced focal cerebral ischemia in rats of group2 was associated with a statistical sign ifi cant increase in serum levels of both TNF-alpha and IL-6 as compared to normal controls. Pretreatment of rats with rosiglitazone in group3 resulted in a statistical significant reduction of the TNF-alpha and IL-6 levels as compared to group2 [This reflects that the ischemic neuronal injury is associated with massive inflammatory processes that lead to brain damage]. And treatment with rosiglitazone could have an anti-inflammatory neuroprotective role. Considering the brain tissue levels of GR, GSH and GPx, which are tissue oxidant defense mechanisms, the present study showed that focal cerebral ischemia in rats of group2 led to a statistical signfi cant reduction in their levels as compared to control group indicating that cerebral ischemia and reperfusion are responsible for oxidative stress by generation of free radicals which culminate to serious damaging effect and overproduction of free radicals takes the upper hand and predominates the detoxication and scavenging capacity of cellular antioxidant enzymes. Treatment of rats with rosiglitazone before induction of focal cerebral ischemia led to a statistical significant increase in the brain tissue levels of defense antioxidant enzymes as GR and GPx as well as GSH assuming its potential neuroprotective role which could be due to its ability to increase the natural defense mechanisms in case of ischemic oxidative stress. PPAR-gamma agonist [rosiglitzone] could be the drug of use in stroke therapy due to its potential to influence multiple molecular mechanisms by its ability to minimize both the inflammation and oxidative stress and at the same time promotes the antioxidant defense mechanisms and protein chaperones

Evaluation of calcitonin gene- related peptide in hypertension: a clinical and experimental study

Calcitonin gene-related peptide [CGRP] is an extremely potent vasodilator neuropeptide that is widely distributed in the perivascular sensory nerves. To clarify the exact role of CGRP in hypertension in both essential hypertension patients and experimentally induced hypertension in rats. 15 patients with untreated essential hypertension and 15 age and sex matched healthy controls were subjected to physical examination, resting ECG, two-dimensional echocardiography, abdominal ultrasound, Doppler study of renal vessels, and laboratory tests including estimation of serum CGRP, malondialdehyde [MDA; as an oxidative stress marker], renal functional parameters and other essential investigations. In the experimental study, hypertension was induced in 15 male albino rats by uninephrectomy and 0.9% saline in drinking water for 6 weeks [uninephrectomy-salt model]. 15 matched healthy male albino rats [controls] were sham operated and given tap water. Rats were subjected to mean arterial pressure [MAP] measurement, using a pressure transducer, and laboratory tests including serum CGRP, MDA and renal function tests. Compared with normotensive controls, essential hypertension patients had a significantly higher mean serum creatinine [P= 0.011], urinary albumin excretion [UAE], and serum MDA versus a significantly reduced CGRP [P<0.001]. Echocardiography revealed subtle hypertensive findings in only 3 patients. All ECGs were normal. Hypertensive rats showed a significantly higher mean blood urea, serum creatinine, UAE, serum MDA, and also CGRP than control rats [P<0.001]. In hypertensive patients, the only observed correlation was a positive correlation between the systolic blood pressure and serum MDA [r =0.52, P =0.037]. In hypertensive rats, a positive correlation was observed between each of MAP, UAE and serum MDA [r =0.65, P =0.008 and r =0.62, P = 0.012] and also between MAP and serum CGRP [r =0.59, P =0.017], versus an inverse correlation between UAE and CGRP [r = -0.54, P =0.026]. In addition, a strongly positive correlation was observed between serum MDA and CGRP in the hypertensive rats [r =0.77, P<0.001]. Patients with essential hypertension have diminished CGRP levels. Hypertension is associated with increased oxidative stress. CGRP is important in protection against hypertension-induced renal damage. These data shed light on a potentially therapeutic role of CGRP and may be antioxidants in the management of hypertension, including the use of medications that can enhance CGRP release, or increase the vascular sensitivity to this neuropeptide

Changes in urinary deoxypyridinoline [DPD] and serum osteocalcin levels in cadmium chloride induced liver damage in rats before and after vitamin D therapy

Chronic liver diseases have an increased prevalence of metabolic bone diseases in the form of osteopenia and osteoporosis, however, there is little information about the mechanisms of these effects. The present study was aimed to investigate the importance of changes of urinary deoxypyridinoline [Dpd] and serum osteocalcin levels in experimentally induced hepatocellular injury in rats by cadmium chloride [CdCl[2]] as well as to clarify the effect of l,25 [OH][2] D[3] administration. Thirty adult male albino rats were used. The study included 3 groups each of 10 rats, group 1 was normal rats used as a control group, group 2 consisted of rats with induced hepatic damage by CdCl[2] [0.1 mg/kg subcutaneously for 4 weeks] and group 3 consisted of rats with CdCl[2]induced damage and treated with 1,25 [OH][2] D[3] administration [0.1 micro g/kg orally once daily for one week]. Blood and urine samples were collected from all rats at the end of the experiment to measure the levels of the following parameters: serum alanine and aspartate aminotransferases [ALT and AST], urinary Dpd levels as well as serum osteocalcin levels. The results of the present study showed that CdCl[2] induced a significant elevation in the mean values of ALT and AST. Urinary Dpd levels were significantly high after CdCl[2] injection. On the other hand, serum osteocalcin levels were significantly reduced especially in group 2 as compared to the other groups. The present study showed that administration of 1,25 [OH][2] D[3] to group 3 lead to reduction in levels of urinary Dpd and increased levels of serum osteocalcin but did not affect levels of serum transaminases. It was concluded that CdCl[2] induced hepatocellular injury is associated with increased bone resorption and decreased bone formation. Administration of 1.25 [OH][2] D[3] can stop these changes by preventing the progression of bone dystrophy associated with hepatocellular damage