Nashwa Barakat

Effects of combined erythropoietin and epidermal growth factor on renal ischaemia/reperfusion injury: a randomized experimental controlled study

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Activation of nuclear factor erythroid 2-related factor 2 (Nrf2) and Nrf-2-dependent genes by ischaemic pre-conditioning and post-conditioning: new adaptive endogenous protective responses against renal ischaemia/reperfusion injury

To investigate the impact of ischaemic pre‐conditioning (Ipre) and post‐conditioning (Ipost) on expression of nuclear factor erythroid 2‐related factor 2 (Nrf2) gene and its dependent genes, haem oxygenase‐1 (HO‐1) and NADPH‐quinone oxidoreductase‐1 (NQO‐1); inflammatory cytokines TNF‐α, IL1β and ICAM‐1; and apoptotic markers such as caspase‐3 in renal ischaemia/reperfusion (I/R) injury.

Renal ischaemia/reperfusion injury: possible role of aquaporins.

Renal ischaemia/reperfusion (I/R) injury is a common problem that occurs when blood flow is interrupted to the kidney in case of kidney transplantation, aortic cross‐clamping and shock with subsequent resuscitation. Renal I/R injury is a complex conditions which includes the onset of an inflammatory process, which is associated with impairment of concentrating ability of the kidney and impairment of solute transport. Characteristically, renal I/R injury is associated with marked reduction in the protein expression of renal aquaporins (AQPs) mainly (AQP1, AQP2 and AQP3), and solute transporters were observed in this condition and could account for the impaired urinary concentration that observed in this condition. Recently, many agents were tested for a possible protective effect against this insult such as erythropoietin (EPO), α‐melanocyte‐stimulating hormone (α‐MSH) and α‐lipoic acid which were proved to prevent downregulation of AQPs and solute transporters. The aim of this short review is to outline the potential pathophysiological role of AQPs in renal I/R injury and to put a spotlight on the modulation of renal functions impairment in renal ischaemia by new drugs that prevent downregulation of AQPs.

Ischaemia-reperfusion injury in renal transplantation: the role of nitric oxide in an experimental rat model

To investigate the role of nitric oxide (NO) in ischaemia‐reperfusion (I/R) injury in a renal transplant rat model, as I/R injury is a common consequence of renal transplantation and NO has many protective properties that might protect the kidney after I/R injury.

Ionized alkaline water: new strategy for management of metabolic acidosis in experimental animals.

Metabolic acidosis can occur as a result of either the accumulation of endogenous acids or loss of bicarbonate from the gastrointestinal tract or the kidney, which represent common causes of metabolic acidosis. The appropriate treatment of acute metabolic acidosis has been very controversial. Ionized alkaline water was not evaluated in such groups of patients in spite of its safety and reported benefits. So, we aimed to assess its efficacy in the management of metabolic acidosis in animal models. Two models of metabolic acidosis were created in dogs and rats. The first model of renal failure was induced by ligation of both ureters; and the second model was induced by urinary diversion to gut (gastrointestinal bicarbonate loss model). Both models were subjected to ionized alkaline water (orally and by hemodialysis). Dogs with renal failure were assigned to two groups according to the type of dialysate utilized during hemodialysis sessions, the first was utilizing alkaline water and the second was utilizing conventional water. Another two groups of animals with urinary diversion were arranged to receive oral alkaline water and tap water. In renal failure animal models, acid‐base parameters improved significantly after hemodialysis with ionized alkaline water compared with the conventional water treated with reverse osmosis (RO). Similar results were observed in urinary diversion models as there was significant improvement of both the partial pressure of carbon dioxide and serum bicarbonate (P = 0.007 and 0.001 respectively) after utilizing alkaline water orally. Alkaline ionized water can be considered as a major safe strategy in the management of metabolic acidosis secondary to renal failure or dialysis or urinary diversion. Human studies are indicated in the near future to confirm this issue in humans.

Protection against renal ischaemia/reperfusion injury: A comparative experimental study of the effect of ischaemic preconditioning vs. postconditioning

Abstract Objective: To compare the effect of ischaemic preconditioning (Ipre) vs. ischaemic postconditioning (Ipost) on renal ischaemia/reperfusion (I/R) injury in rats. Materials and methods: In all, 120 male Sprague–Dawley rats were classified into four groups of 30 rats each, designated sham, control, Ipre and Ipost. Renal function, including serum creatinine, blood urea nitrogen (BUN), creatinine clearance (CrCl), fractional Na excretion (FENa) and renal histopathology were measured at 2, 24 and 48 h after ischaemia. Markers of lipid peroxidation (malondialdehyde, MDA), superoxide dismutase (SOD) and reduced glutathione (GSH) were measured in kidney tissues during the same intervals. Results: Ipre caused a significant improvement in renal function, as indicated by a significant decrease in serum creatinine, BUN and FENa, with a significant increase in CrCl. However, Ipost caused no significant improvement in renal function. Morphologically Ipre caused a marked significant improvement in the renal tubular damage score compared to Ipost. Also, Ipre caused a significant decrease in MDA, and significant increase in GSH and SOD when compared to Ipost. Conclusion: Ipre is more potent than Ipost for improving the renal injury induced by I/R. Ipre caused a marked improvement in renal function and morphology, while Ipost caused a minimal improvement in morphology only. Moreover, Ipre caused a marked and significant reduction in oxidative stress in kidney tissues, while Ipost caused a minimal reduction.

RECOVERABILITY OF RENAL FUNCTION AFTER RELIEF OF CHRONIC PARTIAL UNILATERAL URETERAL OBSTRUCTION: STUDY OF THE EFFECT OF ANGIOTENSIN RECEPTOR BLOCKER (LOSARTAN)

OBJECTIVES To evaluate the effect of angiotensin receptor blocker (losartan) on renal function during and after relief of partial unilateral ureteral obstruction (PUO). METHODS A total of 32 male mongrel dogs were classified into 3 groups: sham (8), control (12; left PUO + no medications), and study (12; left PUO + losartan). Dogs of the study and control groups were subjected to 4 weeks of PUO. After that, they were reopened and subjected to Lich-Grigoir ureterovesical reimplantation and then were killed by the end of 32 weeks after relief of obstruction after being evaluated at basal condition; fourth week of obstruction; and at 4, 8, and 32 weeks after relief of obstruction by measurement of selective creatinine clearance (CCr), selective renographic clearance (RC), and renal resistive index. Sham group underwent sham surgery at 4 and 32 weeks and evaluated as the other 2 groups. RESULTS Sham surgery showed no significant effect on any of the evaluated parameters. Compared with the control, losartan saved reduction in CCr by 11% and RC by 20% of the basal value by the end of the fourth week of obstruction, respectively. Moreover, compared with the control, losartan enhanced regain of CCr by 26% and RC by 26% also of the basal value at 32 weeks after relief of fourth week obstruction, respectively. In addition, the increase in renal resistive index was significantly less in the losartan group. CONCLUSION Losartan decreases the deterioration of renal function in PUO and enhances recoverability of renal function after relief of obstruction.

Remote limb ischemic preconditioning (rIPC) activates antioxidant and antiapoptotic genes and inhibits proinflammatory cytokine genes in renal ischemia/reperfusion injury.

The mechanisms underlying the renoprotective effect for remote limb ischemic preconditioning (rIPC) against renal ischemia/reperfusion injury need further elucidation. In our work, one hundred and twenty male Sprague Dawley rats were randomized into 3 groups; sham, I/R group (left renal 45 min ischemia) and rIPC (as I/R group with 3 cycles of left femoral ischemic PC just before renal ischemia). Rats were sacrificed at 2 h, 24 h, 48 h and 7 days. Serum creatinine and urea were measured at the baseline and endpoints. Also, histopathological examination and assessment of the expression of inflammatory cytokines e.g. TNF-α, IL-1β and ICAM-1 and antioxidant genes: Nrf2, HO-1 and NQO-1 and anti-apoptotic gene Bcl-2 in left kidney were done by the end of experiment. The results of this study demonstrated that, rIPC caused significant improvement in serum creatinine and BUN levels and in the expression of antioxidant genes and Bcl-2 antiapoptotic gene with significant attenuation of pro-inflammatory cytokines and histopathological damage score at all-time points compared to I/R group (p ≤ 0.05). In conclusion, inhibition of inflammatory cytokine (TNF-α, IL-1β and ICAM-1) formation and activation of antioxidant genes: Nrf2, HO-1 and NQO-1 and anti-apoptotic gene Bcl-2 could be possible underlying mechanisms for the renoprotective effect of rIPC.

Role of combination of l-arginine and α-tocopherol in renal transplantation ischaemia/reperfusion injury: a randomized controlled experimental study in a rat model

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Systemic and renal haemodynamic changes in renal schemia/reperfusion injury: impact of erythropoietin

The objective of this study was to investigate the effects of erythropoietin (EPO) on systemic and renal hemodynamics in a rat model of renal ischemic/reperfusion (I/R) injury. We used 30 male Sprague-Dawley rats distributed among the following 3 groups (10 rats per group): (i) the sham-operated group, (ii) the control group (I/R injury only), and (iii) the EPO-treated group (I/R injury with 1500 U EPO·(kg body mass)⁻¹ on day 0, and 500 U·kg⁻¹ on days 2 and 4 after ischemia). Renal function, arterial blood pressure (ABP), renal plasma flow (RPF), renal blood flow (RBF), and renal vascular resistance (RVR) were measured on days 1, 2, and 7 after ischemia. The expression of endothelial NO synthase (eNOS) and histopathology of kidney were evaluated on day 7. The contractility of aortic strips was recorded from the different groups. The results show that renal function and histopathology were significantly improved after treatment with EPO. Compared with the control group, the EPO-treated group showed a significant increase in RPF, RBF, haematocrite, ABP, eNOS expression, and a decrease in RVR (p < 0.05).The response of aortic strips to the relaxant effect of acetylcholine was improved in the EPO-treated group. In conclusion, treatment with EPO improves renal function and renal haemodynamics in renal I/R injury, and causes significant rise of ABP and haematocrite value.