Related Experiment Videos
Antiischaemic effect of defibrotide treatment in rat kidney
Abstract:
The authors previously demonstrated the protective activity of defibrotide (a profibrinolytic and antithrombotic drug) on endothelial cells. In the present work they examine the efficacy of defibrotide in protecting rat kidney from ischaemic/reperfusion injury by studying the modifications of intrarenal adenine nucleotide levels. Right renal ischaemia of 60 min and reperfusion of 30 min were induced in adult male Wistar rats. Defibrotide was administered as a bolus through a catheter inserted into the left femoral vein 5 min before the beginning of ischaemia at the dose of 32 mg/kg and continuously infused during ischaemia/reperfusion through the same vein at the final dose of 32 mg/kg in 5 ml of saline at the rate of 3 ml/h. Rats treated with vehicle of the drug were used as controls. At the end of postischaemic reperfusion, the ischaemic and left kidneys were rapidly removed and frozen in liquid nitrogen. Tissue extracts were prepared, and their ATP, ADP, AMP, cAMP, NAD+, and NADH contents were determined by using luminescence methods. In controls, ATP intrarenal levels were significantly higher in the left kidney than in the ischaemic organ of the same rat (3405 +/- 320 vs. 378 +/- 36 nmol/g fresh tissue and mean +/- s.e.m. of 10 experiments). Defibrotide treatment significantly protected ischaemic kidneys from the drop in ATP intrarenal content (1465 +/- 147 vs. 3124 +/- 303 nmol/g fresh tissue measured in the left kidney).
Insights
Defibrotide, a profibrinolytic and antithrombotic drug, protects rat kidneys from ischemic/reperfusion injury. It significantly preserved intrarenal ATP levels in kidneys subjected to ischemia and reperfusion.
Area of Science:
- Nephrology
- Pharmacology
- Biochemistry
Background:
- Defibrotide exhibits protective effects on endothelial cells.
- Ischemic/reperfusion injury is a significant cause of kidney damage.
- Adenine nucleotide levels are critical indicators of cellular energy status.
Purpose of the Study:
- To evaluate the efficacy of defibrotide in preventing rat kidney damage from ischemia/reperfusion injury.
- To investigate the impact of defibrotide on intrarenal adenine nucleotide levels during renal ischemia/reperfusion.
Main Methods:
- Adult male Wistar rats underwent 60 minutes of right renal ischemia followed by 30 minutes of reperfusion.
- Defibrotide was administered intravenously before and during the ischemia/reperfusion period.
- Intrarenal levels of ATP, ADP, AMP, cAMP, NAD+, and NADH were quantified using luminescence methods.
Main Results:
- Control rats showed a significant decrease in intrarenal ATP levels in the ischemic kidney compared to the non-ischemic kidney.
- Defibrotide treatment significantly attenuated the drop in ATP levels in the ischemic kidneys.
- ATP levels in defibrotide-treated ischemic kidneys were substantially higher than in controls.
Conclusions:
- Defibrotide demonstrates a protective effect against renal ischemia/reperfusion injury in rats.
- The drug's protective mechanism involves preserving intrarenal adenine nucleotide levels, particularly ATP.
- Defibrotide holds potential as a therapeutic agent for preventing kidney damage associated with ischemia/reperfusion events.