Effect of Dexmedetomidine on Lung Tissue Lower Extremity Ischemia Reperfusion Injury in Streptozotocin Induced Diabetic Rats
Abstract
Objective: The aim of our study was to investigate the effects of dexmedetomidine on lung tissue in rat’s lower extremity after undergoing an ischemia reperfusion (I/R) injury.
Material and methods: After obtaining ethical committee approval, 24 Wistar albino rats (200-270 gr) were randomly divided into four groups: (Control (Group C), diabetes-control (Group DC), diabetes I/R (Group DIR), and diabetes-I/R-dexmedetomidine (Group DIRD). In diabetes groups, single-dose (55 mg/kg) streptozotocin was administered intraperitoneally. Rats with a blood glucose level above 250 mg/dl at the 72nd hour were accepted as diabetic. At the end of four weeks, laparotomy was performed in all rats. Nothing else was done in Group C and DC. In Group DIR, ischemia reperfusion was produced via two-hour periods of clamping and subsequent declamping of infra-renal abdominal aorta. In Group DIRD, 100 μg/kg of dexmedetomidine were administered intraperitoneally.
Results: When the groups’ lung tissue neutrophil infiltration/aggregation light microscopic findings were compared to each other, a significant difference was observed among the groups (p=0.003). When the groups’ lung tissue injury score light microscopic findings were compared, a significant difference was observed among the groups (p=0.001). When groups were compared to each other in terms of lung tissue MDA levels and SOD activities, a significant difference was observed (p=0.002, p=0.018, respectively).
Conclusion: Our results confirm that dexmedetomidine has protective effects against the lung damage resulting from IR in diabetic rats. However, future studies should be conducted to evaluate these effects.
References
Dong X, Xing Q, Li Y, Han X, Sun L. Dexmedetomidine protects against ischemia reperfusion injury in rat skeletal muscle. J Surg Res. 2014;186(1):240-5.
Scheinin M, Kallio A, Koulu M, et al. Sedative and cardiovascular effects of medetomidine, a novel selective alpha 2-adrenoceptor agonist, in healthy volunteers. Br J Clin Pharmacol. 1987;24:443–451.
Jalonen J, Hynynen M, Kuitunen A, Heikkilä H, Perttilä J, Salmenperä M, Valtonen M, Aantaa R, Kallio A. Dexmedetomidine as an anaesthetic adjunct in coronary artery bypass grafting. Anesthesiology. 1997;86(2):331-45.
Francischetti I, Moreno JB, Scholz M, Yoshida WB. Leukocytes and the inflammatory response in ischemia- reperfusion injury. Rev Bras Cir Cardiovasc 2010;25:575-84.
Katz MA. The Expanding Role of Oxygen Free Radicals in Clinical Medicine. West J Med. 1986; 144(4): 441–446.
Önem G, Saçar M, Aybek H, Kocamaz E, Adalı F, Saçkan, KG, Baltalarlı A. Protective effects of cilostazol and levosimendan on lung injury induced by lower limb ischemia-reperfusion. Turk J Thorac Cardiovasc Surg 2012;20(3):577-583
Peng M, Wang YL, Wang CY, Chen C. Dexmedetomidine attenuates lipopolysaccharide-induced proinflammatory response in primary microglia. J Surg Res. 2013;179(1):e219-25.
Wang J, Han Z, Zhou H, Wang N, Ma H. Effective Loading Dose of Dexmedetomidine
to Induce Adequate Sedation in Parturients Undergoing Caesarean Section Under Spinal Anaesthesia. Turk J Anaesthesiol Reanim. 2017;45(5):260-263.
Cai Y, Xu H, Yan J, Zhang L, Lu Y. Molecular targets and mechanism of action of dexmedetomidine in treatment of ischemia/reperfusion injury. Mol Med Rep.2014;9(5):1542-50.
Peng CK, Huang KL, Wu CP, Li MH, Hu YT, Hsu CW, Tsai SH, Chu SJ . Glutamine protects ischemia-reperfusion induced acute lung injury in isolated rat lungs. Pulm Pharmacol Ther. 2011;24:153–61.
Hussain T, Shukla GS, Chandra SV. Effects of cadmium on superoxide dismutase
and lipid peroxidation in liver and kidney of growing rats: in vivo and in vitro studies. Pharmacol Toxicol. 1987 May;60(5):355-8.
Fridovich I. Superoxide radical: an endogenous toxicant. Annu Rev Pharmacol Toxicol. 1983;23:239-57.
Durak I, Canbolat O, Kavutçu M, Oztürk HS, Yurtarslani Z. Activities of total, cytoplasmic, and mitochondrial superoxide dismutase enzymes in sera and pleural fluids from patients with lung cancer. J Clin Lab Anal. 1996;10:17–20.
Steiner G. How can we improve the management of vascular risk in type 2 diabetes: insights from FIELD. Cardiovasc Drugs Ther. 2009;23(5):403-8.
Tapuria N, Junnarkar SP, Dutt N, Abu-Amara M, Fuller B, et al. (2009) Effect of remote ischemic preconditioning on hepatic microcirculation and function in a rat model of hepatic ischemia reperfusion injury. HPB (Oxford) 11: 108–117.
Jiang L, Li L, Shen J, Qi Z, Guo L. Effect of dexmedetomidine on lung ischemia reperfusion injury. Mol Med Rep. 2014; 9(2):419-26.
Gu J, Chen J, Xia P, Tao G, Zhao H and Ma D. Dexmedetomidine attenuates remote lung injury induced by renal ischemia‑reper- fusion in mice. Acta Anaesthesiol Scand 55: 1272‑1278, 2011.
Shen J, Fu G, Jiang L, Xu J, Li L, Fu G. Effect of dexmedetomidine pretreatment on lung injury following intestinal ischemia-reperfusion. Exp Ther Med. 2013;6(6):1359-1364
Yang CL, Tsai PS, Huang CJ. Effects of dexmedetomidine on regulating pulmonary inflammation in a rat model of ventilator-induced lung injury. Acta Anaesthesiol Taiwan. 2008;46(4):151-9.
Emrecan B, Tulukoglu E, Bozok S, et al. Effects of iloprost and pentoxifylline on penal ischemia-reperfusion in rabbit model. Eur J Med Res 2006;11:295.
Fang YZ, Yang S, Wu G, Free radicals, antioxidants and nutrition. Nutrition 2002;18:872-9.
