Korean J Nephrol.  2009 Mar;28(2):96-102.

The Preconditioning with AICAR Protects Against Subsequent Renal Ischemia Reperfusion Injury

• Lee SJ
• Chang YK
• Na KR
• Lee KW
• Suh KS
• Kim SY
• Chang YS
• Shin YT
• Bang BK

Abstract

PURPOSE:Preconditioning due to activation of AMPK might reduce ischemia-reperfusion (I/R) injury in the kidney, based on the key role of AMPK in preserving ATP. To evaluate this possibility, the effect of preconditioning with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), AMPK activator, before sustained ischemia was investigated.
METHODS
Adult male Sprague-Dawley rats weighing approximately 220-250 g were used. To induce renal ischemia, a laparotomy was performed under ketamine and xylazine hydrochloride, and the blood supply to both kidneys was interrupted by placement of vessel clamps at the level of the renal pedicles. Reflow was initiated by removing the clamps. The following experimental groups were defined 1. Acute renal ischemia 0 sec, 10 min, 15 min, 2. AICAR treatment, 3. Sham group (S), 4. Ischemia/ Reperfusion group (I/R), 5. AICAR+I/R group (A+I/R), 6. AraA (Adenine-9-b-D-arabinofuranoside, an AMPK) inhibitor+AICAR+I/R group (AraA+A+I/R)
RESULTS
There was only faint AMPK phosphorylation in the sham group. After 10 minutes of ischemia, or AICAR preconditioning however, Thr172 phosphorylation of AMPK was increased (p<0.05). The serum levels of BUN and creatinine were significantly decreased in AICAR preconditioning group (A+I/R). (128.0+/-7.33 mg/dL, 4.18+/-0.27 mg/dL vs. 90.2+/-11.13 mg/dL, 2.58+/-0.7 mg/dL, p<0.05), but these effects were attenuated by AMPK inhibitor, AraA (AraA+A+I/R group). In quantitative analysis of tubular injury, tubular injury score in AICAR preconditioning group significantly decreased (p<0.05).
CONCLUSION
The AMPK activator AICAR has a protective effect against renal I/R injury.

Keyword

AMP-activated protein kinases; Ischemia; Reperfusion; AICA ribonucleotide

MeSH Terms

Adenosine Triphosphate
Aminoimidazole Carboxamide
AMP-Activated Protein Kinases
Creatinine
Glycosaminoglycans
Humans
Ischemia
Ketamine
Kidney
Laparotomy
Male
Phosphorylation
Rats, Sprague-Dawley
Reperfusion
Reperfusion Injury
Ribonucleotides
Salicylamides
Xylazine
AMP-Activated Protein Kinases
Adenosine Triphosphate
Aminoimidazole Carboxamide
Creatinine
Glycosaminoglycans
Ketamine
Ribonucleotides
Salicylamides
Xylazine