الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
 |  | from | 32 |  |  |
| | | from | 32 | | |
Abstract
Ischemia is an inevitable step during kidney transplantation. When transplanting a kidney from a deceased donor, impairment of blood flow starts with brain death due to severe hemodynamic disturbances in cadaveric donor. Meanwhile, in case of living donor transplantation clamping of renal artery causes an absolute ischemia during harvesting operation. Following the blood flow reconstruction in kidney transplantation, the final stage of injury occurs during reperfusion –so called reperfusion injury.
As it has been widely considered as an inflammatory process, therapies that target specific inflammatory cell types or effector proteins such as complement proteins, chemokines, or adhesion molecules, could ameliorate reperfusion injury in animal models. Prostaglandins and leukotrienes play a key role in the generation of the inflammatory response. Their biosynthesis is significantly increased in inflamed tissues, and they contribute to the development of the cardinal signs of acute inflammation. Simultaneous blockade of both pathways (Cyclooxygenase enzyme and leukotriene receptor) may be associated with an augmented protective effect through preventing different types of mediators responsible for leukocyte recruitment and induction of inflammation (Prostaglandins and leukotrienes).
Celecoxib is a selective COX-2 enzyme inhibitor. Inhibition of cyclooxygenase 2 enzyme is believed to provide a protective role in renal I/R injury. Celecoxib induced inhibition of prostaglandins would suppress the inflammatory response responsible for the renal damage in case of renal I/R injury.
Montelukast is a cystinyl leukotriene 1 receptor blocker. Blocking leukotriene receptors is also believed to provide a renoprotective role in case of renal I/R injury. The mechanism of montelukast induced renoprotection is also believed to be through suppression of the inflammatory response responsible for the pathogenesis of renal reperfusion injury. But, unlike celecoxib, montelukast is working to block leukotriene induced inflammation.
In the present study, a rat model of renal I/R, was used to examine the effect of montelukast, celecoxib and their combination on the devevelopment of kidney dysfunction both biochemically and histologically as well as to determine the effect of these drugs on neutrophil recruitment to the ischemic kidney through measurement of MPO level. Finally the antioxidant effect of the drugs alone and in combination was assessed through measurement of MDA in renal tissues.
The study was carried out on fifty white male albino rats, of body weight ranging 150 – 200 grams. Animals were randomly divided into 5 groups each of 10 rats:
Group Ι Sham operated (normal control group)
In this group, non drug treated animals were subjected to the same surgical procedure as drug treated groups without clamping of the renal artery.
Group ΙΙ I/R injury (positive control group)
This group received orally 1 ml of 2% gum acacia, 5 days before RIRI and serves as a control for group III, IV, V. The reperfusion injury procedure was carried out in day 5 of drug administration..
Group III I/R injury (montelukast treated group)
This group was treated with montelukast 0.5 mg/kg/day in 1 ml of 2% gum acacia, 5 days before RIRI. The reperfusion injury procedure was carried out in day 5 of drug administration.
Group ΙV I/R injury (celecoxib treated group)
This group was treated with celecoxib 1.25 mg/kg/day in 1 ml of 2% gum acacia, 5 days before RIRI. The reperfusion injury procedure was carried out in day 5 of drug administration.
Group V I/R injury (montelukast/celecoxib combination treated group)
This group was treated with both celecoxib 1.25 mg/kg in 1 ml of 2% gum acacia and montelukast 0.5 mg/kg/day in 1 ml of 2% gum acacia 5 days before RIRI. The reperfusion injury procedure was carried out in day 5 of drug administration.
After I/R animals were kept for 24 hours in cages for urine collection. By the end of the experimental period, animals were sacrificed. Blood and kidneys were collected and the following parameters were assessed:
- Renal function testing including: serum urea concentration, serum creatinine concentration and creatinine clearance.
- Renal MPO and MDA concentration.
- Histological assessment of kidney samples.
Results:
- Serum urea concentration assessment: revealed significant increase in serum urea concentration in rats that were subjected to renal I/R injury as compared to the sham operated control group.
- Serum creatinine concentration assessment: revealed significant increase in serum creatinine concentration in rats that were subjected to renal I/R injury as compared to the sham operated control group.
- Creatinine clearance assessment: revealed significant reduction in creatinine clearance in rats that were subjected to renal I/R injury as compared to the sham operated control group.
- Renal MPO assessment: revealed significant increase in renal MPO concentration in rats that were subjected to renal I/R injury as compared to the sham operated control group.
- Renal MDA assessment: revealed significant increase in renal MDA concentration in rats that were subjected to renal I/R injury as compared to the sham operated control group.