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J Korean Soc Emerg Med > Volume 14(3); 2003 > Article
Journal of The Korean Society of Emergency Medicine 2003;14(3): 264-272.
Effect of Melatonin during Recovery of Tissue Injury after Intestine Ischemia-Reperfusion
Yil Young Chen, Myung Chun Kim, Young Gwan Ko, Hyung Hwan Baik, Yong Ho Cho
Department of Emergency Medicine and Biochemistry, School of Medicine, Kyung Hee University, Seoul, Korea. edkmc@chollian.net
It is now well recognized that reperfusion of ischemic tissues initiates a complex series of reactions that can paradoxically injure tissues. Apoptosis occurs in select cell populations during morphologic development and during cellular injury, including oxygen radical exposure, ischemia-reperfusion, and sepsis. Thus, in this study, we examined relation of the melatonin effect to the injection time and the dose, and role of melatonin in apoptosis.
Intestinal ischemia-reperfusion injury was induced in rats by clamping the superior mesenteric artery for 30 minutes. After reperfusion injury for 30 minutes, the experimental group was administered melatonin (10 mg/kg) intraperitoneally and the control group received saline and ethanol. At 30 minutes, 60 minutes, and 90 minutes, 1) pulmonary histological assessments (interstitial PMNs/10HPFs and lung (alveolar) injury score), 2) alveolar microvascular permeability assessments (wet-weignt to dry-weight ratio and lipid peroxidation activity, malondialdehyde, MDA), and 3) western blotting assessments (p53, p21, Bax, and bcl-2) were made. For comparison, long- time (60-minute) reperfusion and double- dosage melatonin (20 mg/kg) were also studied.
The lung injury score was 1.00+/-0 in the melatonin group at 90 minutes and 3.28+/-0.30 in the saline group (p<0.01). The number of sequestered neutrophils was significantly higher in the control group at 90 minutes (34.38+/-16.76/10 HPFs) than in the melatonin-treated group (5.63+/-2.73/10 HPFs; p<0.01). In the melatonin group at 90 minutes, the wet-weight to dry-weight ratio was 4.69+/-0.16, and in the saline group, the ratio was 4.78+/-0.17 (p>0.05). A marked difference was found between the ischemia-reperfusion control group and the experimental group at 90 minutes regarding lipid peroxidation activity (Malondialdehyde, 16.45+/-0.19 micrometer vs 10.93+/-0.11 micrometer, p<0.01). In the melatonin group, p21 expressions were found to be much more than in the control group. But, p53, bcl-2, and Bax expressions were found to be in the control group.
Melatonin injection within 60 min after reperfusion may promote recovery of reperfusion injury, but double-dose melatonin injection was inefficacious. Also, melatonin inhibit apoptosis by p21 expression.
Key words: Ischemic-reperfusion injury, Melatonin, Apoptosis
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