Abstract
A variety of experimental studies have demonstrated the neuroprotective effects of melatonin, based on its antioxidant activity. In a prospective randomized study, the effects of melatonin were investigated in experimental head trauma-induced oxidative stress in rabbits. The experimental study was performed on 30 rabbits. The animals were divided into three groups. Group I (sham procedure): a right parietal craniotomy was performed on each animal, and the dura mater was left intact. Group II: experimental brain trauma (EBT) was performed on each animal using a 1 cm inner diameter × 10 cm long glass tube, through which a 20 g weight (0.5 cm diameter) was dropped onto the brain at the craniotomy site, causing a contusional head trauma. Group III: the same EBT model was performed, but 2.5 mg/kg melatonin was injected intraperitoneally four times (total dose 10 mg/kg); these injections were performed 20 min before the operation, during the trauma, 1 h later and 2 h later. The rabbits were sacrificed after the EBT at 24 h after the brain trauma. The activities of the three principal antioxidant enzymes—catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px)—were determined, and the levels of malondialdehyde (MDA), a product of lipid peroxidation, and glutathione (GSH) were measured in brain homogenates. MDA levels were found to be higher in the EBT group than in the EBT+melatonin group or the sham procedure group. The SOD activity was found to be higher in the EBT group than in the sham procedure group. Enzymatic parameters (except for SOD) were significantly higher in melatonin-treated animals than in EBT animals. GSH levels in melatonin-treated animals were decreased compared with EBT animals. In conclusion, the data indicate that melatonin protects against free radical-mediated oxidative changes in brain tissue by boosting antioxidant enzymes, and in particular lowering lipid peroxidation in rabbits with EBT.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Aebi H (1984) Catalase in vitro. Methods Enzymol 105:121–126
Barlow-Walden LR, Reiter RJ, Abe M, Pablos A, Menendez-Pelaez A, Chen LDB, Poeggeler B (1995) Melatonin stimulates brain glutathione peroxidase activity. Neurochem Int 26:497–502
Beutler E, Duron O, Kelly BM (1963) Improved method for the determination of blood glutathione. J Lab Clin Med 61:882–883
Bullock R (1993) Pathophysiological alterations in central nervous system due to trauma. Schweiz Med Wochenschr 123:449–458
Cadet JL (1988) Free radical mechanisms in the central nervous system: an overview. Int J Neurosci 40(13):18–22
Chan PH, Longar S, Fishman RA (1987) Protective effect of liposome-entrapped superoxide dismutase on posttraumatic edema. Ann Neurol 21:540–547
Drapper HH, Hadley M (1990) Malondialdehyde determination as index of lipid peroxidation. Methods Enzymol 186:421–431
Faden AI (1989) TRH analog YM-14673 improves outcome following traumatic brain and spinal injury in rats: dose response studies. Brain Res 486:228–235
Farooqui AA, Horrocks LA (1998) Lipid peroxides in the free radical pathophysiology of brain diseases. Cell Mol Neurobiol 18(6):599–608
Feeney DM, Boyeson MG, Linn RT, MurrayHM, Dail WG (1981) Responses to cortical injury: methodology and local effects of contusions in the rat. Brain Res 211:67–77
Franceschini D, Skaper SD, Floreani M, Borin G, Giusti P (1999) Further evidences for neuroprotective effects of melatonin. Adv Exp Med Biol 467:207–215
Hall ED (1993) Lipid antioxidants in acute central nervous system injury. Ann Emerg Med 22:1022–1027
Hara H, Kato H, Kogure K (1990) Protective effect of α-tocopherol on ischemic neurol damage in the gerbil hippocampus. Brain Res 510:335–338
Horakova L, Onrejickova O, Barchrrata K, Vajdova M (2000) Preventive effect of several antioxidants after oxidative stress on rat brain homogenates. Gen Physiol Biophys 19(2):195–205
Ikeda Y, Long DM (1990) The molecular basis of brain injury and brain edema: the role of oxygen free radicals. Neurosurgery 27(1):1–11
Ikeda Y, Anderson JH, Long DM (1989a) Oxygen free radicals in the genesis of traumatic and peritumoral brain edema. Neurosurgery 24(5):679–685
Ikeda Y, Bresford KL, Long DM (1989b) Oxygen free radicals in traumatic brain edema. Neural Res 11:213–216
Kontos HA, Wei EP (1986) Superoxide production in experimental brain injury. J Neurosurg 64:803–807
Long DM, Maxwell RF, Choi KS, Cole HO, French LA (1972) Multiple therapeutic approaches in the treatment of brain edeme induced by standard cold lesion. In: Reulen HJ, Schurmann K (eds) Steroids and brain edema. Springer, Berlin Heidelberg New York, pp 87–94
Lowry OH, Rosebrough NJ, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 182:265–268
Maas AIR, Steyerberg EW, Murray GD, Bullock R, Baethmann A, Marshall LF, Teasdale GM (1999) Why have recent trials of neuroprotective agents in head injury failed to show convincing efficacy? A pragmatic analysis and theoretical considerations. Neurosurgery 44(6):1286–1298
Messenge C, Margail I, Verrechia C, Allix M (1998) Protective effect of melatonin in a model of traumatic brain injury in mice. J Pineal Res 25(1):41–46
Meydani SN, Barklund MP, Liu S, Meydani M, Miller R, Cannon JG, Morrow FD, Rocklin R, Blumberg JB (1990) Vitamin E supplementation enhances cell mediated immunity in healthy elderly subjects. Am J Clin Nutr 52:557–563
Nishibe M (1989) Experimental studies on the mechanism of spinal cord ischemia: the state of free radical scavengers. Hokkaido Igaku Zasshi 64:301–308
Okatani Y, Wakatsuki A, Kaneda C (2000) Melatonin increases activites of glutathione peroxidase and superoxide dismutase in fetal rat brain. J Pineal Res 28(2):89–96
Poeggeler B, Reiter RJ, Tan D-X, Chen L-D, Manchester LC (1993) Melatonin, hydroxyl radical-mediated oxidative damage, and aging: a hypothesis. J Pineal Res 14:151–168
Reiter RJ (1991) Pineal melatonin: cell biology of its synthesis and of its physiological interactions. Endocrinol Rev 12(2):151–180
Reiter RJ (1993) Interactions of the pineal hormone melatonin with oxygen-centered free radicals: a brief review. Braz J Med Biol Res 26:1141–1155
Reiter RJ (1994) Pineal function during aging: attenuation of the melatonin rhythm and its neurobiological consequences. Acta Neurobiol Exp 54:31–39
Reiter RJ (1998) Oxidative damage in the central nervous system: protection by melatonin. Prog Neurobiol 56(3):359–384
Sarrafzadeh AS, Thomale UW, Kroppenstedt SN, Unterberg AW (2000) Neuroprotective effect of melatonin on cortical impact injury in the rat. Acta Neurochir (Wien) 142(11):1293–1299
Shin SM, Razdan B, Mishra OP, Johnsen L, Papadopulus MD (1994) Protective effect of α-tocopherol on brain cell membrane function during cerebral cortical hypoxia in newborn piglets. Brain Res 653:45–50
Tan D-X, Poeggeler B, Reiter RJ, Chen L-D, Chen S (1993) Melatonin: a potent, endogenous hydroxyl radical scavenger. Endocrine J 1:57–59
Vural H, Sabuncu T, Arslan SO, Aksoy N (2001) Melatonin inhibits lipid peroxidation and stimulates the antioxidant status of diabetic rats. J Pineal Res 31(3):193–198
Wada K, Alonso OF, Busto R, Panetta J, Clemens JA, Ginsberg MD, Dietrich WD (1999) Early treatment with a novel inhibitor of lipid peroxidation (LY341122) improves histopathological outcome after moderate fluid percussion brain injury in rats. Neurosurgery 45(3):601–608
Zang LY, Cosma G, Gardner H, Vallyathan V (1998) Scavenging of reactive oxygen species by melatonin. Biochim Biophys Acta 1425(3):469–477
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kerman, M., Cirak, B., Ozguner, M.F. et al. Does melatonin protect or treat brain damage from traumatic oxidative stress?. Exp Brain Res 163, 406–410 (2005). https://doi.org/10.1007/s00221-005-2338-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00221-005-2338-2