Abstract
Study design: Experimental animal model to assess ischemic spinal cord injury following occlusion of the thoraco-abdominal aorta.
Objectives: To measure whether melatonin administered to rabbits before and after occlusion exerts an effect on the repair of ischemia–reperfusion (IR) injury.
Setting: Medical Biology Laboratory, Inonu University, Malatya, Turkey
Methods: Rabbits were divided into three IR treatment groups and one sham-operated (ShOp) control group. The three treatment groups had their infrarenal aorta temporarily occluded for 25 min, while the ShOp group had laparotomy without aortic occlusion. Melatonin was administered either 10 min before aortic occlusion or 10 min after the clamp was removed. Physiologic saline was administered to the control animals. After treatment, the animals were euthanized and lumbosacral spinal cord tissue was removed for the determination of relevant enzyme activities.
Results: Malondialdehyde levels, indicating the extent of lipid peroxidation, were found to be significantly increased in the nonmelatonin treated (IR) group when compared to the ShOp group. Melatonin, whether given to pre- or post occlusion groups, suppressed malondialdehyde levels below that of the ShOp group. Catalase (CAT) and glutathione peroxidase (GSH-Px) enzyme activities were increased in the IR group compared to the ShOp group. Melatonin given preocclusion resulted in a significant decrease in both CAT and GSH-Px enzyme levels. The superoxide dismutase (SOD) enzyme activity was decreased in the ischemia–reperfusion treatment group. However, the melatonin treatment increased SOD enzyme activity to levels approximating that of the ShOp group.
Conclusion: To our knowledge, this is the first study that shows the effects of melatonin administered both pre- and postischemia on induced oxidative damage to injured spinal cords. Our data also expands on reports that melatonin administration may significantly reduce the incidence of spinal cord injury following temporary aortic occlusion.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
De La Torre JC . Spinal cord injury. Review of basic and applied research. Spine 1981; 6: 315–335.
Faden AI, Jacobs TP, Holaday J . Opiate antagonist improves neurologic recovery after spinal injury. Science 1981; 211: 493–494.
Faden AI, Jacobs TP, Holaday JW . Thyrotropin-releasing hormone improves recovery after spinal trauma in cats. N Engl J Med 1981; 305: 1063–1067.
Faden AI . TRH analog YM-14673 improves outcome following traumatic brain and spinal injury in rats: dose–response studies. Brain Res 1989; 486: 228–235.
Fujimoto T, Nakamura T, Ikeda T, Takagi K . Potent protective effects of melatonin on experimental spinal cord injury. Spine 2000; 25: 769–775.
Johnson SH, Kraimer JM, Graeber GM . Effects of flunarizine on neurological recovery and spinal cord blood flow in experimental spinal cord ischemia in rabbits. Stroke 1993; 24: 1547–1553.
Kasai H, Nishimura S . DNA damage induced by asbestos in the presence of hydrogen peroxide. Gann 1984; 75: 841–844.
Katircioglu SF et al. Effects of prostacyclin on spinal cord ischemia: an experimental study. Surgery 1993; 114: 36–39.
Kochar A, Zivin JA, Lyden PD, Mazzarella V . Glutamate antagonist therapy reduces neurologic deficits products by focal central nervous system. Arch Neurol 1988; 45: 148–153.
McCord JM . Oxygen-derived free radicals in post-ischemic tissue injury. N Engl J Med 1983; 312: 59–63.
Kouchoukos NL, Rokkas CK . Descending thoracic and thoraco-abdominal aortic surgery for aneurysm or dissection how do we minimize the risk of spinal cord injury? Semin Thorac Cardiovasc Surg 1993; 5: 47–54.
Cuevas P, Carceller-Benito F, Reimers D . Administration of bovine superoxide dismutase prevents sequelae of spinal cord ischemia in the rabbit. Anat Embryol 1989; 179: 251–253.
Cuevas P, Reimers D, Carceller F, Iimenez A . Ischemic reperfusion injury in rabbit spinal cord. Protective effect of superoxide dismutase on neurological recovery and spinal infarction. Acta Anat 1990; 137: 303–310.
Lim KH et al. Prevention of reperfusion injury of the ischemic spinal cord. Use of recombinant superoxide dismutase. Ann Thorac Surg 1986; 42: 282–286.
Taoka Y et al. Superoxide radicals play important roles in the pathogenesis of spinal cord injury. Paraplegia 1995; 33: 450–453.
Barlow-Walden LR et al. Melatonin stimulates brain glutathione peroxidase activity. Neurochem Int 1995; 26: 497–502.
Reiter RJ, Acuna-Castroviejo Tan DX, Burkhardt S . Free radical-mediated molecular damage. Mechanisms for the protective actions of melatonin in the central nervous system. Ann NY Acad Sci 2001; 939: 200–215.
Tan DX et al. Significance of melatonin in antioxidative defence system: reactions and products. Biol Signals Recept 2000; 9: 137–159.
Zivin JA, DeGirolami U . Spinal cord infarction. A highly reproducible stroke model. Stroke 1980; 11: 200–202.
Chen LD et al. Melatonin prevents the suppression of cardiac Ca (2+)-stimulated ATPase activity induced by alloxan. Am J Physiol 1994; 267: 57–62.
Uchiyama M, Mihara M . Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. Anal Biochem 1978; 86: 271–278.
Lowry OH, Rosenbrough NJ, Farr AL, Randall RJ . Protein measurement with the Folin phenol reagent. J Biol Chem 1951; 193: 265–275.
McCord JM, Fridovich I . Superoxide dismutase. An enzymic function for erythrocuprein (Hemocuprein). J Biol Chem 1969; 244: 6049–6055.
Luck H . Catalase. In: Bergmayer HU (ed). Methods of Enzymatic Analysis. 2nd edn. Academic press: New York 1963, pp 885–888.
Lawrance RA, Burk RF . Glutathione peroxidase activity in selenium deficient rat liver. Biochem Biophys Res Commun 1976; 71: 952–958.
Connolly JE . Prevention of paraplegia secondary to operation on the aorta. J Cardiovasc Surg (Torino) 1986; 27: 410–417.
Crawford ES et al. Thoracoabdominal aortic aneurysms: preoperative and intraoperative factors determining immediate and long-term results of operations in 605 patients. J Vasc Surg 1986; 3: 389–404.
Svensson LG et al. Cross-clamping of the thoracic aorta. Influence of aortic shunts, laminectomy, papaverine, calcium channel blocker, allopurinol, and superoxide dismutase on spinal cord blood flow and paraplegia in baboon. Ann Surg 1986; 204: 38–47.
Tator CH, Fehling MG . Review of the secondary injury theory of acute spinal cord trauma with emphasis on vascular mechanisms. J Neurosurg 1991; 75: 15–26.
Verdant A et al. Surgery of the descending thoracic aorta. Spinal cord protection with the Gott shunt. Ann Thorac Surg 1988; 42: 147–154.
Kaynar MY et al. Changes in the activity of antioxidant enzymes (SOD, GPx, CAT) after experimental spinal cord injury. Tokushima J Exp Med 1988; 41: 133–136.
Barut S et al. Lipid peroxidation in experimental spinal cord injury. Time–level relationship. Neurosurg Rev 1993; 16: 53–59.
Hall ED, Braughler JM . Effects of intravenous methylprednisolone on spinal cord lipid peroxidation and (Na++ K+)-ATPase activity. J Neurosurg 1982; 57: 247–249.
Tuzgen S et al. The effect of epidural cooling on lipid peroxidation after experimental spinal cord injury. Spinal Cord 1998; 36: 654–657.
Marini CP, Conningham IN . Issues surrounding spinal cord protection. Adv Cardiac Surg 1993; 4: 89–106.
Oldfield EH, Pllinkett RJ, Nylander Jr WA, Meacham WF . Barbiturate protection in acute experimental spinal cord ischemia. J Neurosurg 1982; 56: 511–516.
Reiter RJ, Tan DX, Manchester LC . Biochemical reactivity of melatonin with reactive oxygen and nitrogen species: a review of the evidence. Cell Biochem Biophys 2001; 34: 237–256.
Scott MD, Lubin BH, Zuo L, Kuypers FA . Erythrocyte defence against hydrogen peroxide: preeminent importance of catalase. J Lab Clin Med 1991; 118: 7–16.
Slater TF . Free-radical mechanisms in tissue injury. Biochem J 1984; 222: 1–15.
Nishibe M . Experimental studies on the mechanism of spinal cord ischemia: the state of free radical scavengers. Hokkaido Igaku Zasshi 1989; 64: 301–308.
Althaus JS et al. The use of salicylate hydroxylation to detect hydroxyl radical generation in ischemic and traumatic brain injury. Mol Chem Neuropathol 1993; 20: 147–162.
Marshall KA et al. Evaluation of the antioxidant activity of melatonin in vitro. Free Radio Biol Med 1996; 21: 307–315.
Tan DX et al. The pineal hormone melatonin inhibits DNA-adduct formation induced by the chemical carcinogen safrole in vivo. Cancer Lett 1993; 70: 65–71.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Erten, S., Kocak, A., Ozdemir, I. et al. Protective effect of melatonin on experimental spinal cord ischemia. Spinal Cord 41, 533–538 (2003). https://doi.org/10.1038/sj.sc.3101508
Published:
Issue date:
DOI: https://doi.org/10.1038/sj.sc.3101508
Keywords
This article is cited by
-
The effects of apigenin administration on the inhibition of inflammatory responses and oxidative stress in the lung injury models: a systematic review and meta-analysis of preclinical evidence
Inflammopharmacology (2022)
-
Comparison of the neuroprotective effects of brimonidine tartrate and melatonin on retinal ganglion cells
International Ophthalmology (2018)
-
Melatonin Inhibits Neural Cell Apoptosis and Promotes Locomotor Recovery via Activation of the Wnt/β-Catenin Signaling Pathway After Spinal Cord Injury
Neurochemical Research (2017)
-
The effect of melatonin on spinal cord after ischemia in rats
Spinal Cord (2016)
-
Studies on protection against ischemia reperfusion injury after SCI
Spinal Cord (2016)
