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KMID : 0359920090280020103
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Korean Journal of Nephrology
2009 Volume.28 No. 2 p.103 ~ p.112
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Erythropoietin (EPO) Attenuates Renal Injury in an Experimental Model of Cisplatin-induced Nephrotoxicity in Rats
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Choi Dae-Eun
Lee Kang-Wook
Suh Kwang-Sun
Na Ki-Ryang
Shin Young-Tai
Lee Young-Mo
Chung Sa-Rah
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Abstract
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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+/-.33 mg/dL, 4.18+/-.27 mg/dL vs. 90.2+/-1.13 mg/dL, 2.58+/-.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.
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KEYWORD
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Apoptosis, Cisplatin, Erythropoietin, Inflammation
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