Protective effect of lutein on spinal cord ischemia-reperfusion injury in rats

Document Type: Original Article


1 Neurophysiology Research Center, Department of Anatomy, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran

2 Department of Anatomy, Urmia University of Medical Sciences, Urmia, Iran

3 Department of Biochemistry, Urmia University of Medical Sciences, Urmia, Iran


Objective(s): Paraplegia is deterioration in motor or sensory function of the lower limbs that can occur after modification of a thoracoabdominal aortic aneurysm. The purpose of this survey was to determine the protective action of lutein on spinal cord ischemia-reperfusion (I-R) damage.
Materials and Methods: Thirty-five male rats were distributed into five groups: intact, sham, dimethyl sulfoxide (I-R+DMSO), low dose lutein (I-R+0.2 mg/kg lutein), and high dose lutein (I-R + 0.4 mg/kg lutein). Thirty minutes before surgery, a single dose lutein or DMSO was administered to rats of experimental groups. Next, the abdominal aorta was clamped exactly under the left renal artery and proximal to the abdominal aortic bifurcation for 60 min. All animals were evaluated by neurological function and histological and biochemical examinations at 72 hr after I-R.
Results: The mean motor deficit index (MDI) scores in lutein groups were lower compared with the DMSO group (P<0.001). Plasma level of malondialdehyde in lutein groups decreased compared with the DMSO group (P<0.05). Plasma level of total antioxidative capacity was increased in the high lutein group compared with low dose lutein and sham groups (P<0.05). Mean number of normal motor neurons in lutein groups was greater compared with the DMSO group (P<0.001). There was a significant negative correlation between MDI scores and the number of normal neurons (r= -0.764, P<0.001).
Conclusion: Findings of the present study demonstrate that lutein may support spinal cord neurons from I-R damage.


Main Subjects

1. Di Luozzo G. Visceral and spinal cord protection during thoracoabdominal aortic aneurysm repair: clinical and laboratory update. J Thorac Cardio Vasc Surg 2013;145:135-138.
2. Liu Z, Wang W, Wu J, Zhou K, Liu B. Electroacupuncture improves bladder and bowel function in patients with traumatic spinal cord injury: results from a prospective observational study. Evid Based Complement Alternat Med 2013;  543174. doi: 10.1155/2013/543174.
3. Orem BC, Pelisch N, Williams J, Nally JM, Stirling DP. Intracellular calcium release through IP3R or RyR contributes to secondary axonal degeneration. Neurobiol Dis 2017;106:235-243.
4. Esterberg R, Linbo T, Pickett SB, Wu P, Ou HC, Rubel EM, et al. Mitochondrial calcium uptake underlies ROS generation during aminoglycoside-induced hair cell death. J Clin Invest 2016;126:3556-3566.
5. Zhou Z, Liu C, Chen S, Zhao H, Zhou K, Wang W, et al. Activation of the Nrf2/ARE signaling pathway by probucol contributes to inhibiting inflammation and neuronal apoptosis after spinal cord injury. Oncotarget 2017; 8:52078-52093.
6. Saito T, Saito S, Yamamoto H, Tsuchida M. Neuroprotection following mild hypothermia after spinal cord ischemia in rats. J Vasc Surg 2013;57:173-181.
7. Romangnoli S, Ricci Z, Pinelli F, Stefano P, Rossi A, Bevilacqua S. Spinal cord injury after ascending aorta and aortic arch replacement combined with antegrade stent grafting: role of postoperative cerebrospinal fluid drainage. J Card Surg 2012; 27:224-227.
8. Saito T, Tsuchida M, Umehara S, Kohno T, Yamamoto H, Hayashi J. Reduction of spinal cord ischemia/reperfusion injury with simvastatin in rats. AnesthAnalg 2017;113:565-567.
9. Farjah GH, Salehi S, Ansari MH, Pourheidar B. Protective effect of Crocus sativus L. (Saffron) extract on spinal cord ischemia-reperfusion injury in rats. Iran J Basic Med Sci 2017;20:334-337.
10. Ogura W, Itagaki S, Kurokawa T, Noda T, Hirano T, Mizuno S, et al. Protective effect of lutein on ischemia-reperfusion injury in rat small intestine. Biol Pharm Bull 2006;29:1764-1766.
11. Sommerburg O, Keunen JE, Bird AC, van Kuijk FJ. Fruits and vegetables that are sources for lutein and zeaxanthin: the macular pigment in human eyes. Br J Ophthalmol 1998;82:907-910.  
12. Li SY, Fu ZJ, Ma H, Jang WC, So KF, Wong D, et al. Effect of lutein on retinal neurons and oxidative stress in a model of acute retinal ischemia/reperfusion. Invest Ophthalmol Vis Sci 2009;50:836-843.
13. Tan D, Yu X, Chen M, Chen J, Xu J. Lutein protects against severe traumatic brain injury through anti-inflammation and antioxidative effects via ICAM-1/Nrf-2. Mol Med Rep 2017;16:4235-4240.
14. Richer S, Devenport J, Lang JC. Last II: Differential temporal responses of macular pigment optical density in patients with atrophic age-related macular degeneration to dietary supplementation with xanthophylls. Optometry 2007; 78:213-219.
15. Dilsiz N, Sahaboglu A, Yildiz MZ, Reichenbach A. Protective effects of various antioxidants during ischemia/reperfusion in the rat retina. Graefes Arch Clin Exp Ophthalmol 2006;244:627-633.
16. Chung RWS, Leanderson P, Lundberg AK, Jonasson L. Lutein exerts anti-inflammatory effects in patients with coronary artery disease. Atherosclerosis 2017; 262:87-93.
17. Niu M, Li S, Niu Q, Xu S, Xiao J, Ding L, et al. Preventive effects of lutein on liver toxicity in mice induced by arsenic. Wei Sheng Yan Jiu 2015;44:615-619.
18. Liu H, Liu W, Zhou X, Long X, Kuang X, Hu J, et al. Protective effect of lutein on ARPE-19 cells upon H2O2-induced G2/M arrest. Mol Med Rep 2017;16:2069-2074.
19. Taira Y, Marsala M. Effect of proximal arterial perfusion pressure on function, spinal cord blood flow, and histopathologic changes after increasing intervals of aortic occlusion in the rat. Stroke 1996;27:1850-1858.
20. Yagi K. Assay for blood plasma or serum. Methods Enzymol 1984;105: 328-331.
21. Hirose K, Okajima K, Taoka Y, Uchiba M, Tagami H, Nakano K, et al. Activated protein C reduces the ischemia/reperfusion-induced spinal cord injury in rats by inhibiting neutrophil activation. Ann Surg 2000; 232: 272-280.
22. Kim J, Hwang J, Huh J, Nahm SF, Lim C, Park S, et al. Acute normo volemiche modilution can aggravate neurological injury after spinal cord ischemia in rats. Anesth Analg 2012;114:1285-1261.
23. Zhail L, Liu M, Wang T, Zhang H, Li S, Guo Y. Picroside II protects the blood-brain barrier by inhibiting the oxidative signaling pathway in cerebral ischemia-reperfusion injury. PloS One 2017;12:e0174414.
24. Johnson EJ, Neuringer M, Russell RM, Russell RM, Schalach W, Snodderly DM. Nutritional manipulation of primate retinas, III: Effects of lutein or zeaxanthin supplementation on adipose tissue and retina of xanthophylls-free monkeys. Invest Ophthalmol Vis Sci 2005;46:692-702.  
25. Bergman M, Varshavsky L, Gottlieb HE, Grossman S. The antioxidant activity of aqueous spinach extract: chemical identification of active fractions. Phytochemistry 2001;58:143-152.
26. Avlan D, Erdouğan K, Cimen B, DüşmezApa D, Cinel I, Aksӧyek S. The protective effect of selenium on ipsilateral and contralateral testes in testicular reperfusion injury. Pediatr SurgInt 2005;21: 274-278.
27. Kusan C, Ferrari B. Total antioxidant capacity: a biomarker in biomedical and nutritional studies. J Cell Mol Biol 2008;7:1-15.
28. Li SY, Fung FK, Fu ZJ, Wong D, Chan HH, Lo AC. Anti- inflammatory effects of lutein in retinal ischemic/hypoxic injury: in vivo and in vitro studies. Invest Ophthalmol Vis Sci 2012;53:5976-5984.
29. Sun YX, Liu T, Dai XL, Zheng QS, Hui BD, Jiang ZF. Treatment with lutein provides neuroprotection in mice subjected to transient cerebral ischemia. J Asian Nat Prod Res 2014;16:1084-1093.
30. Bulger EM, Maier RV. Antioxidants in critical illness. Arch Surg 2001;136: 1201-1207.
31. Ueno T, Furukawa K, Katayama Y, Suda H, Itoh T. Spinal cord protection: development of a paraplegia-preventive solution. Ann Thorac Surg 1994;58:116-120.
32. Ribaya-Mercado JD, Blumberg JB. Lutein and zeaxanthin and their potential roles in disease prevention. J Am CollNutr 2004; 23:567S-587S.
33. Zhang C, Wang Z, Zhao J, Li Q, Huang C, Zhu L, et al. Neuroprotective effect of lutein on NMDA-induced retinal ganglion cell injury in rat retina. Cell Mol Neurobiol 2016;36:531-540.
34. Melo van Lent D, Leermakers ET, Hofman A, Stricker BH, Brusselle GG, Franco OH, et al. Association between lutein intake and lung function in adults: the Rotterdam study. Br J Nutr 2017;117:720-730.
35. Graydon R, Hogg RE, Chakravarthy U, Young IS, Woodside JV. The effect of lutein- and zeaxanthin-rich foods v. supplements on macular pigment level and serological markers of endothelial activation, inflammation and oxidation: pilot studies in healthy volunteers. Br J Nutr 2012;108:334-342.
36. Abdel-Aal el-SM, Akhtar H, Zaheer K, Ali R. Dietary sources of lutein and zeaxanthin carotenoids and their role in eye health. Nutrients 2013;5:1169-1185.
37. Tan TB, Yussof NS, Abas F, Mirhosseini H, Nehdi IA, Tan CP. Stability evaluation of lutein nanodispersions prepared via solvent displacement method: The effect of emulsifiers with different stabilizing mechanisms. Food Chem 2016; 205:155-162.