Colchicine protects rat skeletal muscle from ischemia/reperfusion injury by suppressing oxidative stress and inflammation

Document Type: Original Article

Authors

Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, No. 2, Fuxue Road, Wenzhou 325000, Zhejiang Province, People’s Republic of China.

Abstract

Objective(s): Neutrophils play an important role in ischemia/reperfusion (IR) induced skeletal muscle injury. Microtubules are required for neutrophil activation in response to various stimuli. This study aimed to investigate the effects of colchicine, a microtubule-disrupting agent, on skeletal muscle IR injury in a rat hindlimb ischemia model.
Materials and Methods: Twenty-one Sprague-Dawley rats were randomly allocated into three groups: IR group, colchicine treated-IR (CO) group and sham operation (SM) group. Rats of both the IR and CO groups were subjected to 3 hr of ischemia by clamping the right femoral artery followed by 2 hr of reperfusion. Colchicine (1 mg/kg) was administrated intraperitoneally prior to hindlimb ischemia in the CO group. After 2 hr of reperfusion, we measured superoxide dismutase (SOD) and myeloperoxidase (MPO) activities, and malondialdehyde (MDA), tumor necrosis factor (TNF)-α and interleukin (IL)-1β levels in the muscle samples. Plasma creatinine kinase (CK) and lactate dehydrogenase (LDH) levels were measured. We also evaluated the histological damage score and wet/dry weight (W/D) ratio.
Results: The histological damage score, W/D ratio, MPO activity, MDA, TNF-α and IL-1β levels in muscle tissues were significantly increased, SOD activity was decreased, and plasma CK and LDH levels were remarkably elevated in both the IR and CO groups compared to the SM group (P<0.05). Colchicine treatment significantly reduced muscle damage and edema, oxidative stress and levels of the inflammatory parameters in the CO group compared to the IR group (P<0.05).
Conclusion: Colchicine attenuates IR-induced skeletal muscle injury in rats.

Keywords


1. Menger MD, Vollmar B. Pathomechanisms of ischemia-reperfusion injury as the basis for novel preventive strategies: is it time for the introduction of pleiotropic compounds? Transplant Proc 2007; 39:485-488.

2. Lin L, Wang L, Bai Y, Zheng L, Zhao X, Xiong X, et al. Pulmonary gas exchange impairment following tourniquet deflation: a prospective, single-blind clinical trial. Orthopedics 2010; 33:395.

3. Zhang X, Jizhang Y, Xu X, Kwiecien TD, Li N, Zhang Y, et al. Protective effects of remote ischemic conditioning against ischemia/-reperfusion-induced retinal injury in rats. Vis Neurosci 2014; 31:245-252.

4. Seekamp A, Warren JS, Remick DG, Till GO, Ward PA. Requirements for tumor necrosis factor-alpha and interleukin-1 in limb ischemia/reperfusion injury and associated lung injury. Am J Pathol 1993; 143:453-463.

5. Clanton TL, Zuo L, Klawitter P. Oxidants and skeletal muscle function: physiologic and pathophysiologic implications. Proc Soc Exp Biol Med 1999; 222:253-262.

6. Carden DL, Granger DN. Pathophysiology of ischaemia-reperfusion injury. J Pathol 2000; 190:255-266.

7. Iwahori Y, Ishiguro N, Shimizu T, Kondo S, Yabe Y, Oshima T, et al. Selective neutrophil depletion with monoclonal antibodies attenuates ischemia/reperfusion injury in skeletal muscle. J Reconstr Microsurg 1998; 14:109-116.

8. Altinor S, Ozturkcan S, Hah MM. The effects of colchicine on neutrophil function in subjects with recurrent aphthous stomatitis. J Eur Acad Dermatol Venereol 2003; 17:469-470.

9. Paschke S, Weidner AF, Paust T, Marti O, Beil M, Ben-Chetrit E. Technical advance: Inhibition of neutrophil chemotaxis by colchicine is modulated through viscoelastic properties of subcellular compartments. J Leukoc Biol 2013; 94:1091-1096.

10. Lidar M, Livneh A. Familial Mediterranean fever: clinical, molecular and management advancements. Neth J Med 2007; 65:318-324.

11. Schlesinger N, Schumacher R, Catton M, Maxwell L. Colchicine for acute gout. Cochrane Database Syst Rev 2006; 18:CD006190.

12. Caner JE. Colchicine inhibition of chemotaxis. Arthritis Rheum 1965; 8:757-764.

13. Malawista SE, Bodel PT. The dissociation by colchicine of phagocytosis from increased oxygen consumption in human leukocytes. J Clin Invest 1967; 46:786-796.

14. Goldfinger SE, Howell RR, Seegmiller JE. Suppression of metabolic accompaniments of phagocytosis by colchicine. Arthritis Rheum 1965; 8:1112-1122.

15. Reibman J, Haines KA, Rich AM, Cristello P, Giedd KN, Weissmann G. Colchicine inhibits ionophore-induced formation of leukotriene B4 by human neutrophils: the role of microtubules. J Immunol 1986; 136:1027-1032.

16. Gillespie E, Lichtenstein LM. Histamine release from human leukocytes: studies with deuterium oxide, colchicine, and cytochalasin B. J Clin Invest 1972; 51:2941-2947.

17. Erkanli K, Kayalar N, Erkanli G, Ercan F, Sener G, Kirali K. Melatonin protects against ischemia/reperfusion injury in skeletal muscle. J Pineal Res 2005; 39:238-242.

18. Kozower BD, Kanaan SA, Tagawa T, Suda T, Grapperhaus K, Daddi N, et al. Intramuscular gene transfer of interleukin-10 reduces neutrophil recruitment and ameliorates lung graft ischemia-reperfusion injury. Am J Transplant 2002; 2:837-842.

19. Strieter RM, Kunkel SL, Bone RC. Role of tumor necrosis factor-alpha in disease states and inflammation. Crit Care Med 1993; 21:S447-463.

20. Li C, Jackson RM. Reactive species mechanisms of cellular hypoxia-reoxygenation injury. Am J Physiol Cell Physiol 2002; 282:C227-241.

21. Daddi N, Suda T, D'Ovidio F, Kanaan SA, Tagawa T, Grapperhaus K, et al. Recipient intramuscular cotransfection of naked plasmid transforming growth factor beta1 and interleukin 10 ameliorates lung graft ischemia-reperfusion injury. J Thorac Cardiovasc Surg 2002; 24:259-269.

22. Sadoshima J. The role of autophagy during ischemia/reperfusion. Autophagy 2008; 4:402-403.

23. Ma JQ, Ding J, Zhang L, Liu CM. Protective effects of ursolic acid in an experimental model of liver fibrosis through Nrf2/ARE pathway. Clin Res Hepatol Gastroenterol 2015; 39:188-197.

24. Bolcal C, Yildirim V, Doganci S, Sargin M, Aydin A, Eken A, et al. Protective effects of antioxidant medications on limb ischemia reperfusion injury. J Surg Res 2007; 139:274-279.

25. Dong X, Xing Q, Li Y, Han X, Sun L. Dexmedetomidine protects against ischemia-reperfusion injury in rat skeletal muscle. J Surg Res 2014; 186:240-245.

26. Zhou Z, Liu Y, Miao AD, Wang SQ. Protocatechuic aldehyde suppresses TNF-alpha-induced ICAM-1 and VCAM-1 expression in human umbilical vein endothelial cells. Eur J Pharmacol 2005; 513:1-8.

27. Chai H, Wang Q, Huang L, Xie T, Fu Y. Ginsenoside Rb1 inhibits tumor necrosis factor-alpha-induced vascular cell adhesion molecule-1 expression in human endothelial cells. Biol Pharm Bull 2008; 31:2050-2056.

28. Strieter RM, Kunkel SL, Showell HJ, Remick DG, Phan SH, Ward PA, et al. Endothelial cell gene expression of a neutrophil chemotactic factor by TNF-alpha, LPS, and IL-1 beta. Science 1989; 243:1467-1469.

29. Yurttutan S, Ozdemir R, Canpolat FE, Oncel MY, Uysal B, Unverdi HG, et al. Protective effects of colchicine in an experimental model of necrotizing enterocolitis in neonatal rats. J Surg Res 2013; 183:156-162.

30. Forrat R, Sebbag L, Ferrera R, Hadour G, Canet E, Tabib A, et al. Effect of colchicine on circulating and myocardial neutrophils and on infarct size in a canine model of ischemia and reperfusion. J Cardiovasc Pharmacol 1996; 27:876-883.

31. Pratt J, Roux M, Henneguelle E, Stutzmann JM, Laduron PM. Neuroprotective effects of colchicine in the gerbil model of cerebral ischaemia. Neurosci Lett 1994; 169:114-118.

32. Kurt RK, Dogan AC, Dogan M, Albayrak A, Kurt SN, Eren F, et al. Protective effect of colchicine on ovarian ischemia-reperfusion injury: an experimental study. Reprod Sci 2015; 22:545-550.

33. Ouyang Y, Wang W, Bhuta S, Chang YH. Mechanism of action of colchicine. VI: Effect of colchicine on generation of leukotriene B4 by human polymorphonuclear leukocytes. Clin Exp Rheumatol 1989; 7:397-402.

34. Mikenberg I, Widera D, Kaus A, Kaltschmidt B, Kaltschmidt C. TNF-alpha mediated transport of NF-kappaB to the nucleus is independent of the cytoskeleton-based transport system in non-neuronal cells. Eur J Cell Biol 2006; 85:529-536.

35. Jackman RW, Rhoads MG, Cornwell E, Kandarian SC. Microtubule-mediated NF-kappaB activation in the TNF-alpha signaling pathway. Exp Cell Res 2009; 315:3242-3249.

36. Mollinedo F, Nieto JM, Andreu JM. Cytoplasmic microtubules in human neutrophil degranulation: reversible inhibition by the colchicine analogue 2-methoxy-5-(2',3',4'-trimethoxyphenyl)-2,4,6-cycloheptatrien-1- one. Mol Pharmacol 1989; 36:547-555.

37. Reibman J, Haines KA, Gude D, Weissmann G. Differences in signal transduction between Fc gamma receptors (Fc gamma RII, Fc gamma RIII) and FMLP receptors in neutrophils. Effects of colchicine on pertussis toxin sensitivity and diacylglycerol formation. J Immunol 1991; 146:988-996.

38. Das D, Pemberton PW, Burrows PC, Gordon C, Smith A, McMahon RF, et al. Antioxidant properties of colchicine in acute carbon tetrachloride induced rat liver injury and its role in the resolution of established cirrhosis. Biochim Biophys Acta 2000; 1502:351-362.