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

Oxidative stress and nitric oxide deficiency in inflammation of chronic renal failure. Possible preventive role of L-arginine and multiple antioxidants

To evaluate the effect of L-arginine and multiple antioxidants on the inflammatory cytokines level, renal functions, blood pressure and dyslipidemia in chronic renal failure [CRF] rats. This study was carried out between December 2007 and November 2008 in the Department of Physiology, Faculty of Medicine, King Saud University, Kingdom of Saudi Arabia. Chronic renal failure was induced in 40 rats by renal mass reduction [RMR] and 10 rats were sham operated. Renal mass reduction rats were treated for 12 weeks by L-arginine and/or a mixture of antioxidants [L-carnitine, Catechin, Vitamins E and C] and the effect of the treatments on plasma cytokines, soluble intercellular adhesion molecule-1 [sICAM-1], nitrate [NO2] and nitrites [NO3], lipid profile, blood pressure, and renal function was examined. Chronic renal failure increased plasma Interleukin [IL]-1alpha, IL-1beta, IL-6, tumor necrosis factor-alpha, soluble intercellular adhesion molecule-1 [sICAM-1] levels and decreased anti-inflammatory cytokines IL-4 and 10 levels. In addition, hypertension, and dyslipidemia were found. L-arginine treatment improved kidney functions, decreased systolic blood pressure and decreased inflammatory cytokines levels. Antioxidants administration decreased inflammatory cytokines and sICAM-1 levels and increased IL-4 levels. Combined use of L-arginine and the antioxidants mixture were very effective in their tendency to recover normal values of kidney functions, plasma cytokines, sICAM-1, blood pressure, NO2/NO3, cholesterol and triglycerides concentrations. Restoration of the pro-oxidant/ antioxidants balance with increased NO bio-availability counteracts inflammation, renal impairment and dyslipidemia in CRF. This may open new perspectives for the role of antioxidants and NO precursors in the treatment of uremia and its complications

Role of H2 receptors in the regulation of vascular endothelial growth factor level in experimental peptic ulcer in rats

Peptic ulcer is one of the most common clinical diseases. The incidence rate of peptic ulcer has been on the rise over the last two decades. The repair of gastric ulcer requires the reconstitution of epithelial structures and underlying connective tissue, including vessels and muscle layers. This complicated sequence of events requires a high degree of coordination among different cell types, which is regulated by several factors, the most important and best recognized has been vascular endothelial growth factor [VEGF], also some major proinflammatory cytokines namely tumor necrosis factor alpha [TNF-alpha]and interleukin-l0 [lL-10]. This study was carried out to study the role of H2 receptors on the expression of VEGF and proinflammatory cytokines in experimental peptic ulcer using the H2 receptor stimulant [histamine] and H2 receptor blocker [ranitidine]. This study was conducted on 40 adult male albino rats weighing from 200-250 grams each. Animals were divided into 4 groups each of 10 rats namely: group 1; normal healthy rats used as control, group 2; rats with experimental peptic ulcer without treatment, group 3; rats with experimental peptic ulcer treated with H2 receptor stimulant histamine, and group 4; rats with experimental peptic ulcer treated with H2 receptor antagonist ranitidine. Rats from all groups were sacrificed on the fourth day after the induction of peptic ulcer. Histamine significantly increased serum VEGF levels in group 3 rats as compared to all other studied groups. Histamine also significantly increased serum IL-10 levels while it decreased serum TNF-alpha in experimental peptic ulcer rats. Ranitidine significantly decreased serum VEGF levels in group 4 rats as compared to histamine treated group 3 rats but showed no significant difference in serum VEGF levels as compared to either to normal control or in untreated peptic ulcer rats. However, ranitidine increased the levels of both serums IL-10 and TNF-alpha as compared to group 2, although it reversed the actions of histamine on both cytokines decreasing IL-10 and increasing TNF-alpha serum levels. It can be concluded that histamine may exhibit protective effect against gastric ulcer through increasing VEGF levels and enhancing angiogenesis. This gastroprotection could be related to stimulation of H2 receptors. Ranitidine could provide gastroprotection through other mechanisms such as the powerful and selective inhibition of gastric acid secretion. However, its effect on VEGF production should be considered.Ranitidine, in combination with histamine, should be extensively studied because it may reduce ulcer. area by reducing inflammatory cytokine levels while increasing gastric mucosal blood flow

Changes in renal angiotensinii level in response to caffeic acid phenethyle ester in diabetic rats and its implications on diabetic nephropathy

Diabetic nephropathy [DN] is a microvascular complication of diabetes that represents a major cause of morbidity and mortality in diabetic subjects and is a leading cause of end-stage renal disease in the western countries. Hyperglycemia and tissue injury increase tissue angiotensin II [Ang II] that stimulates the proliferation of kidney cells and the expression of growth factors or cytokines, which may directly or indirectly contribute to the renal 'changes seen in diabetes. The current study aimed to investigate the effect of caffeic acid phenethyester [CAPE] an active component of bee propolis, on diabetic renal injury via examining its effect on renal and plasma AngH levels, blood glucose and insulin levels, proteinurea, albuminurea, and kidney functions in diabetic rats. This study was performed on 30 male Wister rats [300-325g] in weight. Diabetes was induced in 20 rats using 60mg/kg i.p streptozotocin [STZ] in 20 [microl of 0.05 M sodium citrate, pH 4.5. Ten control healthy rats [Group 1] were injected i.p with - 20 microl of the buffer. Diabetic animals studied in this work were divided into 2 experimental groups [n=10 in each] namely, Group 2 that received no treatment and Group 3 that was injected daily with CAPE 10 microl/kg i.p for 4 weeks. Body weight and blood glucose level were measured at the beginning of the study and then every week for all animals. Blood and 24 hrs urine samples and, kidney tissue were collected at the end of the study for measurement of plasma and kidney tissue Ang II levels, serum insulin, urea and creatinine levels. Proteins, albumin and creatinine levels were also measured in urine. Untreated diabetic rats showed significant increase in blood glucose, and significant decrease in serum insulin levels and they fail to gain weight by the end of the study. In addition they showed significant increase in renal and plasma angiotensin II levels and significant increase in urinary protein and albumin loss with a significant increase in serum urea and creatinine levels in comparison to control rats. CAPE treatment for 4weeks was able to significantly decreased plasma and renal Ang II, and significantly increase serum insulin, and decreased blood glucose levels. In addition both urinary protein and albumin loss decreased significantly in the treated rats. CAPE treatment was able to decrease blood glucose, plasma and renal Ang II levels and to increase serum insulin levels and to ameliorate the manifestations of renal impairment associated with diabetes in rats. This may be through its antioxidant, antiproliferative and anti-inflammatory effects. These findings help us to suggest that supplementation of CAPE as an adjuvant therapy to diabetic persons may be promising in helping a better glycemic control and decreasing the renal complications of this wide spread metabolic disorder

potential anti-inflammatory effect of tetrahydrobiopetrin administration in renal mass reduction -induced chronic renal failure

Elevated C-reactive protein [CRP], as a marker of persistent inflammation, predicts cardiovascular and over all mortality in chronic kidney disease patients. The present study aimed to investigate the impact of tetrahydrobiopetrin [BH4] supplementation on the markers of inflammation and on the histological picture of the kidney in chronic renal failure [CRF] induced in rats by subtotal nephrectomy [SNx]. This study was performed at the Faculty of Medicine, King Saud University. CRF was induced by 5/6 subtotal nephrectomy [SNx] in 20 male Wister rats and other 10 rats were sham operated by flank incision and served as controls. Ten SNx rats received l0mg/kg BH4 i.p daily for 4 weeks. Plasma CRP, IL-6, malondialdehyde [MDA], and kidney functions were measured in all rats. Histopathological examination of the kidney tissues was also performed. Untreated CRF rats showed significant elevation of plasma CRP, IL-6 and MAD levels and significant decrease in plasma albumin and total protein levels, tubuloglomerularfibrosis and, interstitial tubular infiltration with inflammatory cells in comparison to the sham operated rats. BH4 treatment significantly decreased CRP, IL-6 and MAD levels and also decreased the tubuloglomerular fibrosis and interstitial inflammation in treated CRF rats. Supplementation with exogenous BH4 decreases markers of inflammation and protects the kidney against post- renal mass reduction histologic damage. Restoration of intracellular BH4 balance could normalize NO production. Therefore, BH4 might be a promising strategy in attenuating inflammation in CRF. This may decrease endothelial dysfunction and limit the associated cardiovascular morbidity and mortality in this disease

effect of vitamine E, L-arginine, N-nitro L-arginine methyle ester and forskolin on endocrine and metabolic changes of rats exposed to acute cold stress

It is a well documented fact that under stress conditions the hypothalamic-pituitary-adrenal axis [HPA] and the sympathetic nervous system [SNS] are stimulated. This results in a series of neural and endocrine adaptations known as the stress response. The current study assessed the effects of acute cold stress on adrenomedullin [ADM] levels in plasma and peripheral tissues [kidneys and heart] of rats, as well as on blood glucose, cholesterol, triglycerides [TG], total proteins both before and after intraperitoneal administration of each of the following: vitamin-E, L-arginine, forskolin and L-NAME. Methods:The current study was conducted in the Department of Physiology, Faculty of Medicine, King Saud University, Saudi Arabia, between September 2003 and March 2004. We observed 6 groups of Wistar rats for their plasma ADM, tissue plasminogen activator [t-PA], total protein, glucose and cholesterol levels. Following exposure to cold stress [-10 degree celcius for 3 hours].Results:Acute cold stress produced a significant increase in ADM levels in plasma, heart and kidney tissues of rats. Furthermore, acute cold stress produced a reduction in cholesterol and plasma protein levels. On the other hand, acute cold stress caused an increase in TG, glucose plasma levels and tissue plasminogen activator [t-PA]. We found hormonal and metabolic changes caused by cold exposure to be decreased or even prevented after vitamin E treatment or after changing nitric oxide [NO] level by L-arginine or L-NAME treatment.Conclusion:The results suggest a regulatory or protective role for ADM in counteracting HPA activation following a variety of physiological and psychological stressors. Oxidative stress or changes in intracellular signals as NO, cyclic-AMP may play a role in explaining some of the metabolic and hormonal changes occurring during acute cold stress