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Background and Objectives Bone marrow-derived mesenchymal stem cells (BM-MSCs) are adult multipotent non-haematopoietic stem cells that have regeneration potential. The current study aimed to detect the ability of BM-MSCs to improve kidney and cardiac functions in adult rats with established chronic kidney disease. Methods Rats were divided into sham-operated control, untreated sub totally nephrectomised and treated sub totally nephrectomised groups. Body weight, kidney and cardiac tissue weights, plasma creatinine and urea levels and arterial blood pressure were measured. ECG was recorded, and an in vitro isolated heart study was performed. Results: Stem cell treatment decreased the elevated plasma creatinine and urea levels and decreased systolic, diastolic and mean arterial blood pressure values. These changes were accompanied by a decrease in glomerular hypertrophy with apparent normal renal parenchyma. Additionally, BM-MSCs shortened Q-To and Q-Tc intervals, all time to peak tension values, the half relaxation value at 30 min of reperfusion and the contraction time at 15 and 30 min of reperfusion. Moreover, stem cell treatment significantly increased the heart rate, QRS voltage, the peak tension at the 15- and 30-min reperfusion time points and the peak tension per left ventricle at the 30-min reperfusion time point compared to the pre-ischaemia baseline. BM-MSCs resolve inter muscular oedema and lead to the re-appearance of normal cardiomyocytes. This improvement occurs with the observations of BM-MSCs in renal and heart tissues. Conclusions BM-MSCs can attenuate chronic kidney disease progression and the associated cardiac electrophysiological and inotropic dysfunction.

Background Common bile duct ligation (BDL) is a rat experimental model to induce biliary cirrhosis. Lung fibrosis and pulmonary vascular angiogenesis and congestion are the most common complications of biliary cirrhosis that is known as hepatopulmonary syndrome. The aim of the present work is to investigate the acute lung injury in a BDL model and to investigate the possible protective effect of quercetin on this injury. Methods Twenty-four adult male albino rats of the Wister strain (weighing 150–250 g). Animals were divided into 3 groups, with 8 rats each: Group I: Sham-operated group (control). Group II: Bile duct ligation group (BDL) sacrificed after 28 days from the surgery. Group III: Quercetin-treated bile duct ligation group (Q-BDL) was given orally by gastric gavage in a dose of 50 mg/kg/day, starting from the 4th day of the operation until the 28th day. At the end of the experiment, at day 28, all rats were sacrificed. Lung specimens were processed to measure Endothelin B receptor gene expression by PCR, lung surfactant by ELISA, “eNO” s by immunohistochemistry. Histological assessment was done using; H&E, Masson’s trichrome, PAS, toluidine blue-stained semi-thin sections, transmission electron microscope. Histomorphometric and statistical studies were done. Results BDL group showed significant increase in lung index together with mononuclear cellular infiltration denoting lung inflammatory state. Also, the significant increase in pulmonary endothelial nitric oxide synthase ("eNO" s) area percent and endothelin B receptor (ETB) gene expression indicates enhanced angiogenesis. Pulmonary surfactant concentration was significantly decreased together with thickening of interalveolar septa denoting lung injury and fibrosis. Quercetin led to significant decrease in lung index, pulmonary "eNO" s area percent, ETB gene expression and significant increase in pulmonary surfactant concentration. Quercetin treatment improved histological changes and morphometric measurements, limited mononuclear cellular infiltration and decreased perivascular and perialveolar collagen deposition. Conclusion Quercetin ameliorates the hepatopulmonary syndrome-induced lung injury through its anti-inflammatory, antioxidative and antifibrotic effects.

Back Ground Hypertension and its cardiovascular complications as myocardial infarction are the leading causes of morbidity and mortality worldwide. Reperfusion strategies are the current standard therapy but they result in cardiac ischemia reperfusion injury. Stem cell transplantation has emerged as a promising therapeutic strategy and showed many beneficial effects in different medical disorders as reno-vascular hypertension. Aim of Work To assess the possible protective effects of bone marrow derived mesemchymal stem cells treatment on ischemic/reperfused hearts in hypertensive rats. Materials & Methods 49 adult female Wistar albino rats, were allocated into three main groups: control group, hypertensive untreated (Ht-u) group and hypertensive stem cells (Ht-SCs) treated group. Body weight, arterial blood pressure, ECG recording, isolated heart study with exposure to ischemia reperfusion injury and fluorescence imaging of labeled MSCs in the heart, aorta and liver were performed. Plasma lipid profile, nitric oxide, MDA and SOD levels and cardiac MDA and SOD levels were estimated. Cardiac tissues were weighed. Heart, aorta and liver were histopathologically assessed. Results Ht-SCs treated group demonstrated significant increase in body weight gain %, significant decrease in R voltage, SBP, DBP and MAP sixth week values compared to HT-u group, with DBP and MAP showing non-significance from the control. Significant increase in heart rate basal and all reperfusion values and non-significant increase in basal PT/LVW were detected compared to HT-u group. Basal TPT and HRT were significantly shortened and MFR/LVW was significantly increased than HT-u group, being non-significantly changed from the control denoting systolic and diastolic function improvement.TPT and HRT prolongation and MFR/LVW decrease after IR injury was significantly lower in HT-SC group than HT-u group. This was accompanied by significant decrease in atherogenic index, plasma and cardiac MDA and significant increase in plasma nitrites, SOD and cardiac SOD. BM-MScs were detected in cardiac and aortic tissues. Conclusion Single injection of BM-MScs exerted anti-hypertensive and anti-hypertrophic effects, reduced systolic and diastolic dysfunction after ischemia reperfusion injury and improved coronary flow in hypertensive rats, through homing into aortic tissues mitigating endothelial dysfunction and exerting angiogenic effects and homing into cardiac tissues exerting anti-oxidant, anti-inflammatory and anti-apoptotic effects.

Background: In spite of the claimed cardio-protective effects of ischemic preconditioning (IPC), it is invasive and so using remote ischemic preconditioning (RIPC) may offer an alternative. Meanwhile, RIPC cardio protective role is controversial, with an equivocal underlying mechanism. The hypoxia inducible factor 1 alpha (HIF-1-alpha) which is increased following ischemic insults is claimed as a humoral mediator for RIPC. Objectives:To investigate the effect of remote ischemic pre-conditioning on myocardial ischemia/reperfusion injury in rats, and to elucidate the possible role of hypoxia inducible factor in this protection. Patients and Methods:The present study was performed on 28 adult female albino rats in the same estrus cycle evaluated by vaginal smear, and they were allocated into 3 groups: Group I: control rats subjected to ischemic /reperfusion injury (I/R) only, group II: early RIPC rats (RIPC 2 hours prior to I/R), group III: acriflavine-treated early RIPC rats. Acriflavine is a drug that binds directly to HIF-1 alpha and HIF-2 alpha subunits, thus inhibiting its dimerization and transcriptional activity, and it was injected IP 10 days prior to RIPC. On sacrifice day, ECG was recorded and isolated heart studies were performed. Later, cardiac chambers weight, serum HIF-1-alpha, myocardial perfusate lactate dehydrogenase, and cardiac oxidative markers: Malonaldehyde and glutathione perioxidase were measured.Results: Compared to the control group, the early RIPC group showed significant increase in the heart rate (HR), QTc interval in the ECG recording, glutathione peroxidase and the HIF 1α levels together with reduction in the percent of decrease in PT and PT/LV, in the percent of prolongation in time to peak tension (TPT), perfusate lactate dehydrogenase and MDA levels, while no significant changes were recorded in the heart chronotropic activity, in the percent of half relaxation time (HRT) prolongation, or in the percent of decrease of MFR. Following acriflavine treatment, the effects of RIPC were abolished highlighting the role of HIF-1-alpha in mediating RIPC protective effects. Conclusion:The non-invasive and non-pharmological remote ischemic preconditioning technique can ameliorate the cardiac ischemic reperfusion injury with an obvious role of HIF-1α in mediating these protective effects. ASMAA T. EBRAHIM et al.