ISSN : 1301-5680
e-ISSN : 2149-8156
Turkish Journal of Thoracic and Cardiovascular Surgery     
PREVENTION OF LUNG INJURY BY FK 506 FOLLOWING HIND LIMB ISCHEMIA AND REPERFUSION MODEL IN RATS
Atike TEKELİ, S. AKGÜN, A. CİVELEK, S. İŞBİR, K. AK, A. ÇOBANOĞLU, *G. DEMİRTAŞ, *S. SİRVANCI, *S. ARBAK, **İ. YAYLIM
Marmara Üniversitesi Tıp Fakültesi Kalp Damar Cerrahisi Ana Bilim Dalı, İstanbul
* Marmara Üniversitesi Histoloji Ana Bilim Dalı, İstanbul
** İstanbul Üniversitesi DETAM, İstanbul
Background: The major part of tissue damage occurs upon reperfusion and is mediated by activated neutrophils that release oxygen free radicals. Following hind limb ischemia and reperfusion, injury in the lung due to neutrophil infiltration and oxygen free radicals has been demonstrated in animal models. In addition to being a potent immunosuppressant , FK506 modulates neutrophilic infiltration. To test this effect we looked at the role of FK506 in prevention of lung injury following hind limb ischemia and reperfusion model in rats.

Methods: Twenty-two male Spraque-Dawley rats were randomized to receive FK506 at doses of 0.3 mg/kg/day, 0.5 mg/kg/day, 1mg/kg/day or normal saline via intraperitoneal injections as pretreatment. On the fourth day the animals were subjected to 2 hours of ischemia to their hind limbs using ourniquet method. After 2 hours of ischemia, tourniquets were released and the extremities were reperfused for 2 hours. Lung tissue assays were performed for lipid peroxidation products malondealdehyde (MDA) and conjugated diens (CD), and total glutathione (GSH). Lung tissues were also examined histopathologically under light microscopy.

Results: Animals that were pretreated with FK506 showed the least lipid peroxidation product (MDA 33.92 ± 5.33, p < 0.01). Total glutathione levels and conjugated dien levels showed no significant difference. Histopathologic examination showed less neutrophil infiltration and less lung tissue damage in the study groups.

Conclusion: Lower levels of malondealdehyde (MDA) found in lung tissue suggest that pretreatment with FK506 reduces the production of oxygen free radicals that are accelerated by ischemia and reperfusion. There is no significant effect of FK 506 on glutathione system.

Keywords : Lower limb ischemia-reperfusion, lung injury, FK506
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