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Yayın FK506 to prevent lung injury after hindlimb ischemia and reperfusion in a rat model: An electron microscopic study(SPRINGER, 2004) Akgun, S; Tekeli, A; Isbir, SC; Civelek, A; Ak, K; Sirvanci, S; Arbak, S; Yaylim, I; Arsan, SPurpose. Hindlimb ischemia and reperfusion leads to lung injury in various animal models. We investigated the effectiveness of FK506, an immunosuppressive agent, which also modulates neutrophilic infiltration, in preventing lung injury after hindlimb ischemia and reperfusion in a rat model. Methods. Twenty-seven male Sprague-Dawley rats were randomized to received FK506 at doses of 0.3 mg/kg, 0.5 mg/kg, or 1 mg/kg body weight per day, or normal saline injections, as pretreatment, and there was also a sham group. On the 4th day, the animals were subjected to 2 h of ischemia induced by a tourniquet, followed by reperfusion of the extremities for 2 h. Lung tissue assays were performed for the lipid peroxidation product malondialdehyde (MDA) and total glutathione (GSH). Lung tissues were also examined histopathologically under light and electron microscopy. Results. The MDA levels in the study groups were significantly lower than those in the control group (P < 0.05), but the total GSH levels did not differ significantly among the groups. Histopathologically, there were no significant differences among the groups given different doses of FK506, but there was a significant difference between the control group and all the treatment groups. Conclusion. FK506 ameliorates the lung injury associated with ischemia and reperfusion of the lower limbs, and might have an inhibitory effect on the neutrophils that cause remote organ damage.Yayın Neuroprotective effects of FK-506, L-carnitine and azathioprine on spinal cord ischemia-reperfusion injury(OXFORD UNIV PRESS INC, 2004) Akgun, S; Tekeli, A; Kurtkaya, O; Civelek, A; Isbir, SC; Ak, K; Arsan, S; Sav, AObjective: In our experimental study, we aimed to test the effect of FK506, azathioprine and L-carnitine on protection of spinal cord injury due to ischemia-reperfusion. Methods: Twenty-seven Spraque-Dawley male rats were randomly divided into five groups. They were subjected to spinal cord ischemia by clamping the abdominal aorta for 45 min. Thirty minutes before the aortic clamping, group I received 0.5 mg/kg FK506, group II received 100 mg/kg L-carnitine, group III received 4 mg/kg azathioprine, the fourth group was the control group and received only normal saline injection intravenously and the last group was the sham group. Neurological status was scored by using the Tarlov scoring system. Sections of the lumbar cord were harvested for histopathological grades (1-4), having regard to percentage of the apoptotic cells. Results: Hind-limb motor function had recovered normally 48 h after the operation in all rats which received FK506, azathioprine and L-carnitine prophylactically. In contrast, all rats in the control group had deteriorated to paraplegia by 48 h after the operation (P < 0.05). Histopathologic sections in the involved spinal cord segment showed that a greater number of motor neuron cells were preserved and there were less apoptotic cells in the rats that received FK506, azathioprine and L-carnitine than those in control group. Conclusions: These results suggest that prophylactic use of FK506, azathioprine and L-carnitine protects motor neuron cells from ischemic spinal cord injury. (C) 2003 Elsevier B.V. All rights reserved.