X-Message-Number: 30227 Date: Sun, 30 Dec 2007 21:08:53 -0800 (PST) From: Subject: melatonin for vitrification solutions [An argument could be made for including melatonin in vitrification solutions. Melatonin inhibits reperfusion injury, cold induced cerebral edema, and aids in repair of nerve cells. Melatonin also inhibits the toxicity of cryoprotectants such as ethanol, methanol and glycerol.] J Pineal Res. 2007 Aug;43(1):42-9. Melatonin improves methanol intoxication-induced oxidative liver injury in rats. Kurcer Z, Oguz E, Iraz M, Fadillioglu E, Baba F, Koksal M, Olmez E. Department of Pharmacology, Faculty of Medicine, Harran University, Sanliurfa, Turkey. This study was performed to evaluate the effect of melatonin on methanol-induced liver injury. We evaluated the levels of malondialdehyde (MDA), protein carbonylation (PC), myeloperoxidase (MPO) activities and to assess lipid peroxidation, protein oxidation, neutrophil accumulation and nitrite which is a stable end product of nitric oxide respectively. We also studied superoxide dismutase, catalase, and glutathione peroxidase activities of liver tissue to evaluate the changes in the antioxidant status. Histopathological alterations were also determined. The experiment was performed on Wistar rats, which received intragastric 3 g/kg methanol as a 50% solution in isotonic saline once. After 6 and 24 hr all the drug received and intoxicated rats were killed under anesthesia. Pretreatment with melatonin (10 mg/kg) decreased the MDA levels significantly, restored the PC levels to the control, prevented the increase of nitrite level and MPO activity significantly and reversed to the control levels, prevented the reduction in all of the antioxidant enzyme activities. Additionally in melatonin treated group piecemeal necrosis, lobular lytic necrosis, and portal inflammation returned to normal histologic appearances when compared with methanol administration. In conclusion, melatonin has protective effects against methanol-induced hepatic injury. PMID: 17614834 J Pineal Res. 2005 Nov;39(4):346-52. Comparison of the impact of melatonin on chronic ethanol-induced learning and memory impairment between young and aged rats. Baydas G, Yasar A, Tuzcu M. Department of Physiology, Faculty of Medicine, Firat University, Elazig, Turkey. Chronic alcohol exposure causes functional and structural changes in nervous system which have all been associated with learning and memory impairments. Furthermore, alcohol consumption has been shown to alter the pattern of neural cell adhesion molecules (NCAM) which are involved in memory processes. In the current work, we investigated the effects of melatonin on learning and memory deficits induced by alcohol exposure in young and aged rats. A group of young rats (3 months old) were administered ethanol for 45 days and half of them were co-treated with melatonin. Similar treatments were performed in the aged (19 months old) rats. Morris water maze test and passive avoidance task were used to assess cognitive performance. Lipid peroxidation (LPO) and glutathione (GSH) levels were determined to characterize the level of oxidative stress in the hippocampus and cortex. NCAM levels were determined by Western blotting in the hippocampal homogenates. There was a significant elevation in LPO levels and a reduction in GSH levels in aged and alcohol-exposed rats. Furthermore, both young and aged rats displayed some cognitive impairment when given with alcohol for 45 days. Co-administration of melatonin with ethanol significantly reduced LPO and elevated GSH levels while improving the learning and memory deficits induced by ethanol; the aged rats exhibited a greater response to melatonin supplementation. Moreover, melatonin modulated NCAM expression in hippocampus. Present findings indicate that exposure to ethanol induces learning and memory deficits probably by generating reactive oxygen species and downregulating NCAM 180 in hippocampus of aged rats. Melatonin improves learning and memory deficits and the behavioral responses of rats to melatonin supplementation are age dependent. PMID: 16207289 Life Sci. 2003 May 2;72(24):2707-18. Melatonin and N-acetylcysteine have beneficial effects during hepatic ischemia and reperfusion. Sener G, Tosun O, Sehirli AO, Ka maz A, Arbak S, Ersoy Y, Ayanoglu-D lger G. School of Pharmacy, Department of Pharmacology, Marmara University, Tibbiye Cad. 81010, Istanbul, Turkey. This study was designed to study the effects of Melatonin (Mel) and N-Acetylcystein (NAC) on hepatic ischemia/reperfusion (I/R) injury in rats. For this purpose Wistar albino rats were subjected to 45 minutes of hepatic ischemia followed by 60 minutes of reperfusion period. Melatonin (10 mg/kg) or NAC (150 mg/kg) were administered alone or in combination, intraperitoneally, 15 minutes prior to ischemia and just before reperfusion. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were determined to assess liver functions. Liver tissues were taken for determination of malondialdehyde (MDA) levels, an end product of lipid peroxidation; glutathione (GSH) levels, a key antioxidant; protein carbonyl concentration (protein oxidation) (PO), a specific marker of oxidative damage of proteins; and myeloperoxidase (MPO) activity, as an indirect index of neutrophil infiltration. Plasma ALT and AST activities were higher in ischemia/reperfusion group than in control. They were decreased in the groups given Mel, NAC or the combination. Hepatic GSH levels, significantly depressed by I/R, were elevated to control levels in the combination group, whereas treatment with Mel or NAC alone provided only a limited protection. Hepatic MDA and PO levels, and MPO activity were significantly increased by I/R. The increase in these parameters were partially decreased by Mel or NAC alone, whereas treatment with the combination reduced these values back to control levels. In conclusion, considering the dosages used, Mel appeared to be significantly more potent than NAC in reversing the oxidative damage induced by I/R. Our findings show that Mel and NAC have beneficial effects against the I/R injury and due to their synergistic effects, when administered in combination, may have a more pronounced protective effects on the liver. PMID: 12679188 Childs Nerv Syst. 2008 Jan;24(1):111-7. Epub 2007 May 15. Neuroprotective effects of high-dose vs low-dose melatonin after blunt sciatic nerve injury. Shokouhi G, Tubbs RS, Shoja MM, Hadidchi S, Ghorbanihaghjo A, Roshangar L, Farahani RM, Mesgari M, Oakes WJ. Department of Neurosurgery and Anatomy, Tabriz University of Medical Sciences, Tabriz, Iran. INTRODUCTION: Melatonin, the secretory product of the pineal gland, has potent antioxidant properties. The aim of this study was to compare the effects of low-dose (10 mg/kg) vs high-dose (50 mg/kg) melatonin on early lipid peroxidation levels and ultrastructural changes in experimental blunt sciatic nerve injury (SNI). We believe this to be the first study to assess the dose-dependent neuroprotective effects of melatonin after a blunt peripheral nerve injury. MATERIALS AND METHODS: Rats were randomly allocated into 5 groups of 10 animals each. The SNI only rats underwent a nerve injury procedure. The SNI plus vehicle group received SNI and intraperitoneal injection of vehicle (diluted ethanol) as a placebo. The SNI plus low-dose or high-dose melatonin groups received intraperitoneal melatonin at doses of 10 mg/kg or 50 mg/kg, respectively. Controls had no operation, melatonin or vehicle injection. SNI was induced by clamping the sciatic nerve at the upper border of the quadratus femoris for 2 min. RESULTS: Sciatic nerve samples were harvested 6 h after nerve injury and processed for biochemical and ultrastructural analysis. Trauma increased the lipid peroxidation of the sciatic nerve by 3.6-fold (153.85 +/- 18.73 in SNI only vs 41.73 +/- 2.23 in control rats, P < 0.01). Low (P = 0.02) and high (P < 0.01) doses of melatonin attenuated the nerve lipid peroxidation by 25% and 57.25%, respectively (65.76 +/- 2.47 in high-dose vs 115.08 +/- 7.03 in low-dose melatonin groups). DISCUSSION: Although low-dose melatonin reduced trauma-induced myelin breakdown and axonal changes in the sciatic nerve, high-dose melatonin almost entirely neutralized any ultrastructural changes. CONCLUSION: Our results suggest that melatonin, especially at a dose of 50 mg/kg, has a potent neuroprotective effect and can preserve peripheral neural fibers from lipid peroxidative damage after blunt trauma. With further investigations, we hope that these data may prove useful to clinicians who treat patients with nerve injuries. PMID: 17503055 Ren Fail. 2002 Nov;24(6):735-46. Effects of melatonin administration to rats with glycerol-induced acute renal failure. Ferraz FF, Kos AG, Janino P, Homsi E. Division of Nephrology, Faculdade de Ci ncias M dicas, Universidade Estadual de Campinas, S o Paulo, Brazil. Melatonin, the pineal hormone with antioxidative properties was administered to rats with glycerol-induced myoglobinuric acute renal failure (Gly-ARF). This model is characterized by acute tubular necrosis mediated by heme-iron oxidative stress. Rats received melatonin (20 mg/kg) concomitant and 3 h after glycerol injection. Gly-ARF rats showed at 24 h a 78% reduction in glomerular filtration rate, whereas this decrement was significantly reduced to 35% in the melatonin treated Gly-ARF rats. Tubular function evaluated by tubular reabsorption of sodium and lithium was also preserved in melatonin treated rats. The histologic analysis revealed extensive cortical tubular necrosis that was significantly reduced by melatonin treatment. The renal concentration of malondialdehyde (MDA) was increased 6 h after glycerol injection in Gly-ARF and this elevation was prevented when melatonin was administered. Renal concentration of reduced glutathione (GSH) was decreased at 6 h in Gly-ARF and melatonin did not reverse this decrease. It was concluded that melatonin administration attenuated the renal injury in the glycerol model of acute renal failure and reduced kidney oxidative stress through a GSH-independent mechanism. PMID: 12472196 Neurosurgery. 2001 Dec;49(6):1434-41; discussion 1441-2. Effect of melatonin on cerebral edema in rats. G rg l A, Palaoglu S, Ismailoglu O , Tuncel M, S r c MT, Erbil M, Kilin K. Department of Neurosurgery, School of Medicine, University of Trakya, Edirne, Turkey. OBJECTIVE: Melatonin (5-methoxy-N-acetyltrypamine), a chemical naturally produced in the pineal gland, has been suggested to be a free radical scavenger and an antioxidant. In the present study, the effect of melatonin on cold-induced brain edema was evaluated by determination of cerebral water content, blood-brain barrier permeability, and areas of infarct; the effects were also studied histopathologically. METHODS: Brain edema was produced in rats by creating a lesion via cortical freezing. Animals were separated into four groups: sham-operated (craniectomy only); control (cold injury); sham-vehicle (cold injury plus saline); and melatonin treatment (cold injury plus melatonin). Melatonin was administered (50 mg/kg intraperitoneally) 15 minutes after the cold injury was induced. Twenty-four hours later, tissue samples from the core, from the periphery of the cold-injured hemisphere, and from the contralateral hemisphere symmetrical to the cold injury were obtained. RESULTS: Melatonin treatment reduced edema (mean +/- standard deviation; 86.22 +/- 1.54% in the control group versus 80.78 +/- 2.76% in the melatonin treatment group, P < 0.001) and blood-brain barrier permeability (45.34 +/- 2.75% in the control group versus 38.26 +/- 3.40% in the melatonin treatment group, P < 0.001) at the periphery of cold injury. Area of infarct reduced from 5.84 +/- 0.58% in the control group to 3.30 +/- 0.89% in the melatonin treatment group (P < 0.001). The effect of melatonin was also confirmed histopathologically. CONCLUSION: Melatonin was found to be neuroprotective in instances of cold-induced brain edema. Thus, melatonin may be a valuable therapeutic agent in the treatment of cerebral edema. PMID: 11846944 Neurosci Lett. 2005 Mar 11;376(2):98-101. Epub 2004 Dec 15. Melatonin enhances the in vitro and in vivo repair of severed rat sciatic axons. Stavisky RC, Britt JM, Zuzek A, Truong E, Bittner GD. Section of Neurobiology, The University of Texas at Austin, 1 University Station 0C0920, Austin, TX, 78712-0248, USA. This study examines the effects of several experimental compounds [melatonin (MEL), cyclosporin A (CsA), glial-derived neurotrophic factor (GDNF), and methylprednisolone (MP)] on polyethylene glycol (PEG)-induced repair in vitro and/or in vivo by plasmalemmal fusion (PEG-fusion) of sciatic axons severed by crushing. As measured by conduction of compound action potentials (CAPs) through the lesion site, a significantly (p<0.025) higher percentage (75%) of crushed rat sciatic axons can be repaired in vitro by PEG-fusion following exposure to MEL compared to PEG-fusion of severed sciatic axons in control Krebs saline that contains calcium (CTL=20%). In contrast, no other experimental compound (GDNF: 45%; MP: 42%; CsA: 24%) produces a significant improvement in PEG-fusion success compared to CTL. Further, MEL produces significantly (p<0.001) larger peak CAP amplitudes conducted through the lesion site following PEG-fusion compared to CTL or any other experimental compound in vitro. Additionally, MEL significantly (p<0.025) increases the ability to PEG-fuse sciatic axons in vivo, compared to CTL. Finally, PEG-fusion success in vivo is significantly (p<0.01) greater in calcium-free CTL (CTL-Ca) compared to CTL. PMID: 15698928 Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=30227