الفهرس يوجد فقط 14 صفحة متاحة للعرض العام
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المستخلص
Renal ischemia reperfusion (I/R) injury is one of the most commen causes of ARF which commonly affects patients in many clinical conditions including myocardial ischemia, shock, stroke and renal transplantation. Renal I/R results in increased morbidity, prolonged hospitalizations, and increased mortality.
The pathogenisis of renal I/R injury and strategies for prevention or treatment of this condition have received considerable attention in recent years.
For diagnosis of renal I/R physicians usually rely upon serum markers such as blood urea nitrogen and creatinine concentration, but these markers may not become elevated until more than 24 hours after the insult. This causes failure to delay the development of ischemic ARF before causing irreversible damage, and an effective therapy is not yet available.
HIF-1α is an important transcription complex that is activated in response to hypoxia. Upon activation, HIF may improve the survival of ischemic cells and also promote beneficial adaptive changes by regulation of the expression of a cluster of genes important for tissue adaptation to ischemia. Thus, pharmacological induction of HIF-1α might be a key therapy of renal I/R injury, ameliorating its prognosis.
Among the drugs reported to induce HIF-1α are erythropoietin (EPO), statins as well as desferrioxamine.
Also, inhibition of complement system activation in response to hypoxia is another important strategy to improve the outcome in renal I/R injury as activation of the complement system plays a crucial role in the pathogenesis of renal I/R injury.
Erythropoietin (EPO) is a glycoprotein hormone produced primarily in the kidney. The essential function of EPO is regulation of red blood cells production. In addition to being a hematopoietic factor, EPO has multiple protective effects, such as antiapoptotic, antioxidant, anti-inflammatory, and angiogenic effects.
Statins or 3-hydroxy-3-methyl glutaryl co-enzyme A (HMG-Co A) reductase inhibitors are lipid lowering agents that are widely used in treatment of hypercholesterolemia. It was found that statins have pleiotropic actions independent of lipid lowering affects, including anti-inflammatory, antioxidant and angiogenic action.
Desferrioxamine (DFO) is a chelator that has a high affinity for ferric iron and it has been widely used in iron-overloaded patients with acute iron intoxication or overload due to transfusion-dependent anemia. DFO might confer cytoprotection in various organs including the kidneys by affecting free iron availability.
In the present study, the rat model of renal I/R injury was used to examine the effect of EPO, rosuvastatin and DFO on development of kidney dysfunction as well as to determine the effect of these drugs on transactivation of renal HIF1-α and finally on inhibition of complement activation in response to renal I/R injury in rats.
The study was carried out on fourty white male Wistar albino rats, of body weight ranging from 150–200 grams. Animals were randomly divided into five groups each of eight rats:
Group I: Sham-operated control group
In this group rats were subjected to the same surgical procedure as in renal I/R injury group without clamping of the renal artery.
Group II: Renal ischemia reperfusion (I/R) injury group
This group served as a control for drug-treated renal I/R injury groups.In this group, animals received three doses of intraperitoneal (i.p) injection of physiological saline (0. 9 ٪ NaCl) as the vehicle for the studied drugs, 24 hours, immediately before as well as 24 hours after I/R injury. Renal I/R injury was induced by clamping both renal arteries for 35 minutes then blood flow was restored via clamp removal.
Group III: Erythropoietin (EPO) -treated renal I/R injury group
Animals in this group received three i.p injections of recombinant human EPO in a dose of 5000 units/kg b. wt, 24 hours, immediately before as well as 24 hours after renal I/R injury.
Group IV: Rosuvastatin-treated renal I/R injury group
These animals received three doses of i.p injections of rosuvastatin in a dose of 10 mg/kg b. wt 24 hours, immediately before as well as 24 hours after renal I/R injury.
Group V: Desferrioxamine (DFO) - treated renal I/R injury group
These animals received three i.p injections of DFO in a dose of 100 mg/kg b.wt 24 hours , immediately before as well as 24 hours after renal I/R injury.
After renal I/R injury, animals were kept for 24 hours in metabolic cages for urine collection.
By the end of experimental period, animals will be sacrificed under light ether anesthesia. Blood was collected, kidneys were isolated and the following parameters were assessed: