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European Surgical Research
Research Article
van den Akker E. · Dor F.J.M.F. · IJzermans J.N.M. · de Bruin R.
Introduction Short-term fasting protects against renal ischemia reperfusion injury (IRI). mTOR signaling is downregulated and may be involved in its protective effect. Rapamycin is considered a possible mimetic as it inhibits the mTOR-pathway. This study examines the effect of rapamycin on renal IRI. Methods Mice were divided in four groups : Ad libitum(AL), Fasted (F), AL treated with rapamycin (AL+R) and F treated with rapamycin (F+R). Rapamycin was administered intraperitoneally 24h before bilateral renal IRI was induced. Survival was monitored for 7 days. Renal cell death, regeneration, and mTOR activity were determined 48h after reperfusion. Oxidative stress resistance of HK-2 and PTEC cells after rapamycin treatment was determined. Results All F and F+R mice survived the experiment. Although rapamycin substantially downregulated mTOR-activity, survival in the AL+R group was similar to AL (10%). Renal regeneration was significantly reduced in AL+R but not in F+R. After IRI (48h), pS6K/S6K ratio was lower in F, F+R and AL+R groups compared to AL fed animals (p=0.02). In vitro, rapamycin also significantly downregulated mTOR-activity (p
The Author(s). Published by S. Karger AG, Basel
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