الفهرس 
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Abstract
Acute kidney injury is amajor clinical problem associated with high morbidity and mortality rates.Despite being associatedwith high mortality, AKI isnot usually the direct cause of death.
However, AKI-induced systemic inflammatory response andprogression of damage and dysfunction to remote organs that have been implicated in the high patient mortality.It has been demonstrated that cardiac failure in AKI patients is the major cause of death.
Despite being used widely by most clinicians for managing AKI, evidence for beneficial effects, concerning outcome and mortality, of loop diuretics still lacking even with experimental results suggesting a therapeutic potential. Clinically, diuretics have beenshown to increase the risk of AKIor lack therapeutic benefit in different settings. Considering thisconflict of diuretic effect in managing AKI, it is urgently required to identify agents with possible protective effect in the clinical settings.
Previous studies showed that sitagliptin could ameliorate the deleterious effects induced by renal I/R injuries.However, sitagliptin has been shown toexert cardioprotectiveeffects on isolated cardiac ischemia.In consequence, sitagliptin has been shown to have anti-inflammatory, anti-oxidant, and anti-apoptotic properties.
In addition, allopurinol has been shown to protect against the injury induced by renal I/R in experimental models but furosemide has been widely used clinically.
The current study was focused on
1- Investigating the effects of sitagliptin (treatment and prophylaxis) on the remote myocardial damage induced byrenal I/R injury in rats.
2- Identifying the underlying mechanism of action.
3- The effects of sitagliptin were compared to those of furosemide (widely usedby most clinicians for managing AKI and its powerful anti-inflammatory and anti-apoptotic effects), their combination and allopurinol (due to its potent anti-oxidant activity).
Renal ischemia/reperfusion was induced experimentally in rats by both renal pedicles occlusion for 30 min, followed by 24 h of reperfusion.
Experimental Groups
Adult male wistar rats were randomly distributed into the following groups
1. Negative Control group (n=6)
Normal rats, received oral saline.
2. Sham Operated Control group (n=6)
Rats underwent all surgical procedures without I/R in normal rats and received saline orally.
3. Ischemia /Reperfusion (I/R) groups (n=54)
Ischemia was produced for 30 min, followed by 24 h reperfusion.
Rats were randomly distributed into 9 equal groups as follows
group I: received saline orally.
group II: received sitagliptin (5 mg/kg) orally, administered twice, 5h after reperfusion and 2 h before scarification (the end of reperfusion period).
group III: received sitagliptin (5 mg/kg) orally for 3 consecutive days; then underwent (I/R) procedure at 2 h after the last dose.
group IV: received furosemide (245 mg/kg) orally, administered twice, 5h after reperfusion and 2 h before scarification (the end of reperfusion period).
group V: received furosemide (245 mg/kg) orally for 3 consecutive days; then underwent (I/R) procedure at 2 h after the last dose.
group VI: received allopurinol (50 mg/kg) orally, administered twice, 5h after reperfusion and 2 h before scarification (the end of reperfusion period).
group VII: received allopurinol (50 mg/kg) orally for 3 consecutive days; then underwent (I/R) procedure at 2 h after the last dose.
group VIII: received both sitagliptin (5 mg/kg) & furosemide (245 mg/kg) orally, administered twice, 5h after reperfusion and 2 h before scarification (the end of reperfusion period).
group IX: received both sitagliptin (5 mg/kg) & furosemide (245 mg/kg) orallyfor 3 consecutive days; then underwent (I/R) procedure at 2 h after the last dose.
At the end of reperfusion period both blood samples (followed by serum preparation) and tissue samples (kidney and heart) were collected for measurement of the following parameters:
Serum samples
Renal function: serum urea, creatinine and cystatin c level.
Heart function: Serum LDH, CK-MB and cTnI level.