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Journal of Clinical Neuroscience 15 (2008) 784–790

Laboratory Study

Comparison of the effects of octreotide and melatonin in preventingnerve injury in rats with experimental spinal cord injury

Fatih S. Erol a,*, Metin Kaplan a, Murat Tiftikci a, Huseyin Yakar a,Ibrahim Ozercan b, Necip Ilhan c, Cahide Topsakal a

a Department of Neurosurgery, School of Medicine, Firat University, Elazig 23200, Turkeyb Department of Pathology, School of Medicine, Firat University, Elazig, Turkey

c Department of Biochemistry, School of Medicine, Firat University, Elazig, Turkey

Received 26 April 2007; accepted 1 June 2007

Abstract

In this study, we aimed to investigate the biochemical and histopathological protective effects of octreotide and melatonin in an exper-imental model of spinal cord injury. Fifty- six male albino Wistar rats were divided into four groups. Rats in the G1 group (n = 7; controlgroup) did not undergo any treatment except for anesthesia prior to being killed. Rats in the G2 group (n = 7) underwent laminectomyand aneurysmal clip application at the T4-5 level. G3 group rats (n = 14) were either treated with a 7.5 mg/kg intraperitoneal dose ofmelatonin (Sigma, St. Louis, MO, USA) immediately after laminectomy, then the same dose again on the day following injury(G3a), or given three equal doses over 10 days to achieve a total dose of 7.5 mg/kg/day (G3b). G4 group rats (n = 14) were either treatedwith a 30 lg/kg intraperitoneal dose of octreotide (Sandostatin; Novartis, Istanbul, Turkey) immediately after laminectomy, then thesame dose again on the day following injury (G4a), or given three equal doses over 10 days to achieve a total dose of 30 lg/kg/day(G4b). Rats in the G3 and G4 groups were sacrificed on days 1 and 10 after spinal cord injury (n = 7 at each time point) and spinal cordsamples were obtained. Tissue malonyldialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) levelswere assayed. G3a, G3b and G4b had significantly lower levels of MDA than G2 (p < 0.01). G3b had significantly higher SOD andGSH-Px levels than G2 (p < 0.01). Histopathologically, melatonin significantly reduced necrosis and degeneration in both the initialand late stages (p < 0.01). Octreotide had significant effects on necrosis and degeneration during the late stages, and on edema and con-gestion in both the initial and the late stages of injury (p < 0.01). Melatonin was found to be superior to octreotide with respect to theprevention of congestion, edema, axonal degeneration and necrosis.� 2007 Elsevier Ltd. All rights reserved.

Keywords: Histopathology; Lipid peroxidation; Melatonin; Octreotide; Spinal cord injury

1. Introduction

Traumatic spinal cord injury (SCI) can precipitate seri-ous biochemical and pathological events that result in tis-sue necrosis and functional deficits. Among the earliestbiochemical reactions are hydrolysis of fatty acids frommembrane phospholipids, production of biologically activeeicosanoids, and peroxidation of lipids with formation ofreactive oxygen species (ROS). The latter are the main

0967-5868/$ - see front matter � 2007 Elsevier Ltd. All rights reserved.

doi:10.1016/j.jocn.2007.06.009

* Corresponding author. Tel.: +90 424 233555; fax: +90 424 2388096.E-mail address: fserol@yahoo.com (F.S. Erol).

agents responsible for cellular damage. Superoxide, ferryland hydroxyl anions are the reactive compounds that com-monly cause lipid peroxidation.1,2 Under normal condi-tions, superoxide (O�2 ) anions are generated duringmitochondrial electron transport. There is a balance be-tween the antioxidants and oxidants produced by aerobiccellular systems. One of the antioxidant defense systemsis O�2 dismutase (SOD), which eliminates O�2 by convertingthem to hydrogen peroxide (H2O2). H2O2 is reduced towater by cytosolic antioxidants, catalase, and glutathioneperoxidase (GSH-Px). Concentrations of the products of li-pid peroxidation, for example malonyldialdehyde (MDA),

F.S. Erol et al. / Journal of Clinical Neuroscience 15 (2008) 784–790 785

together with SOD and GSH-Px, can be measured to mon-itor the degree of lipid peroxidation. With the developmentof experimental SCI models and recent advances in SCI re-search, various treatment regimens are now being evalu-ated clinically, such as those involving receptor blockers,physiologic antagonists, inhibitors of biosynthetic path-ways, and membrane-stabilizing drugs. Despite this, noeffective treatment for SCI has been developed. The pathol-ogy associated with SCI has been classified into the initialphase, ischemic phase and repair phase. Acute damagetends to occur in the central, rather than the peripheralregions of the spinal cord. Depending on the amount oftrauma, subacute damage may be limited to central graynecrosis or may progress or evolve to include the neighbor-ing white matter.3

Currently there is still no effective remedy for the neuro-logical deficits that occur after SCI. To the best of ourknowledge, the literature contains no studies comparingthe effects of melatonin and octreotide, which are knownto have lipid antioxidation, antiedema and anti-ischemiceffects. In this study, we aimed to compare the effects ofmelatonin and octreotide in a rat model of SCI.

2. Materials and methods

For this study, 42 male albino Wistar rats weighing 200–250 g were used. Rats were kept in cages at room temper-ature (18–21 �C) and fed with rat chow and water. TheCanadian Council’s guide lines for the care and use ofexperimental animals were followed.4 Subjects were dividedinto four groups. In the first group (G1), the control group(n = 7), rats did not undergo surgery or medical interven-tion, except for anesthesia when the spinal cord tissue sam-ples were taken. In the second group (G2), the injury group(n = 7), the laminectomies and cord injury were performed,then saline was given and spinal tissue samples were takenusing the technique described below. In the third group(G3), the melatonin after injury group (n = 14), rats wereeither treated with a 7.5 mg/kg intraperitoneal dose of mel-atonin (Sigma, St. Louis, MO, USA) immediately afterlaminectomy and cord injury, then the same dose againon the day following injury (G3a), or given three equaldoses over 10 days to achieve a total dose of 7.5 mg/kg/day (G3b). The rats were sacrificed on days 1 and 10 afterinjury (7 rats at each time point) and spinal cord sampleswere obtained. In the fourth group (G4), the octreotideafter injury group (n = 14), rats were either treated with a30 lg/kg intraperitoneal dose of octreotide (Sandostatin;Novartis, Istanbul, Turkey) immediately after laminectomyand cord injury, then the same dose again on the day fol-lowing injury (G4a), or given three equal doses over 10days to achieve a total dose of 30 lg/kg/day (G4b). Thisgroup of rats were sacrificed following the same scheduleas the G3 rats.

Anesthesia was initiated using 50 mg/kg ketaminehydrochloride (Ketalar; Eczacibasi, Istanbul, Turkey) and5 mg/kg xylazine hydrochloride (Rompun; Bayer, Istanbul,

Turkey) injected intramuscularly. One-third of the initialdose was repeated every hour as required. In all animalsin groups G2–4, the spinal cords underwent T3–T6 totallaminectomies and spinal cord injury as described by Rivlinand Tator5 by extradural compression of the exposedspinal cord at the T4–5 level for 30 s using an aneurysmalclip (Yasargil FE 760, Aesculap Inc., Center Valley, PA,USA) with a closing force of 180 g on the cord. For bio-chemical analysis, the spinal cord tissue samples werewrapped in aluminum foil and stored at �20 �C. Tissuesamples were kept in 10% formaldehyde for histopatholo-gical investigation.

2.1. Biochemical investigation

2.1.1. Measurement of tissue MDA levels

Lipid peroxidation in injured spinal cord was estimatedusing the thiobarbituric acid reaction method for MDA de-scribed by Ohkawa et al.6 to give a red species absorbinglight at 535 nm. The MDA results were expressed asnmol/g wet tissue.

2.1.2. Measurement of SOD activity levels

The role of SOD is to accelerate the dismutation of thetoxic superoxide radical (O�2 ) to hydrogen peroxide andmolecular oxygen. The method we used to measure SODactivity levels employs xanthine and xanthine oxidase(XOD) to generate superoxide radicals, which react with2-(4-iodophenyl)-3-(4-nitrophenol)-5-phenyltetrazoliumchloride to form a red formazan dye. The SOD activity isthen measured based on the degree of inhibition of thisreaction. This was accomplished using a RANSOD kit(Randox, Crumlin, UK) according to the method ofDrabkin.7

2.1.3. Measurement of GSH-Px activity levels

GSH-Px activity levels were measured using a RANSELkit (Randox) according to the method of Paglia and Valen-tine,8 in which GSH-Px activity is coupled with the oxida-tion of reduced nicotinamide adenine dinucleotidephosphate (NADPH) by glutathione reductase. The oxida-tion of NADPH was followed spectrophotometrically at340 nm and 37 �C. The reaction mixture consisted of 50mmol potassium phosphate buffer (pH 7), 1 mmol edeticacid (EDTA), 1 mmol NaN3, 0.2 mmol NADPH 1 mmolglutathione and 1 U/mL of glutathione reductase. Absor-bance at 340 nm was recorded for 5 min. Activity was cal-culated from the slopes of the lines as lmol of NADPHoxidized per minute.

2.2. Histopathological investigation

For histopathological investigation, spinal cord tissueswere fixed with buffered 10% formaldehyde solution thenembedded in paraffin and horizontally sectioned at 5-lm.After deparaffinization, samples were stained with hema-toxylin and eosin (H&E) and evaluated under a light

Fig. 1. Tissue malonyldialdehyde (MDA) levels (nmol/g wet tissue)(*p < 0.05 compared with group G2). Data are mean ± SD.

Fig. 2. Superoxide dismutase (SOD) levels (*p < 0.05 compared withgroup G2). Data are mean ± SD.

Fig. 3. Glutathione peroxidase (GSH-Px) levels (*p < 0.05 compared withgroup G2). Data are mean ± SD.

786 F.S. Erol et al. / Journal of Clinical Neuroscience 15 (2008) 784–790

microscope in terms of congestion, edema, axonal degener-ation, and necrosis. All these parameters were calculated interms of the percentage of the damaged surface, and theclassification used was as follows:9 0 (no damage), 1 (slight)� 5%, 2 (minimal) 6–20%, 3 (moderate) 21–50%, 4 (severe)51–75%, 5 (very severe) 76–100%.

2.3. Statistical analysis

SPSS 10.0 software (SPSS, Chicago, IL, USA) was usedfor statistical calculations and graphs. For intergroup com-parisons, Kruskal–Wallis variance analysis was used for sixindependent groups each consisting of 6 30 subjects. Incases where the p-value was <0.05, the groups were com-pared in a 2 � 2 fashion using the Mann–Whitney U-test.In order to prevent significance inflation, p < 0.01 was ac-cepted as significant. Intragroup comparisons were per-formed initially using Friedman variance analysis and ap-value of <0.05. Thereafter, Wilcoxon’s rank test wasused for 2 � 2 comparisons, and to prevent significanceinflation, p < 0.01 was accepted as significant. Results areexpressed as mean ± standard error (SE) of the mean.

3. Results

3.1. Biochemical investigation findings

3.1.1. Tissue MDA levels

Tissue MDA levels in the spinal cord samples werefound to be significantly higher in group G2 (laminectomygroup) than in group G1 (control) group (p < 0.01). TissueMDA levels in the spinal cord samples were significantlylower in groups G3a and G3b (melatonin-treated) than ingroup G2 (p < 0.01). Tissue MDA levels in the spinal cordsamples were lower in groups G4a and G4b (octreotide-treated) than in group G2. The difference was statisticallysignificant for group G4b (p < 0.01) but not for groupG4a (p > 0.05). Group G3a had a significantly lower tissueMDA level than group G4a (p < 0.01), but there was nosignificant difference between groups G3b and G4b(p > 0.05). Hence, melatonin had a greater effect thanoctreotide on MDA level when administered immediatelyafter injury, but there was no significant difference betweenthe two agents when administered later after injury (Fig. 1).

3.1.2. SOD levelsSpinal cord SOD levels were significantly lower in group

G2 than in group G1 (p < 0.01). SOD levels were higher ingroup G3a than in group G2, although the difference wasnot statistically significant (p > 0.05). There was a signifi-cant difference between groups G3b and G2, with groupG3b having a much higher SOD level than group G2(p < 0.01). Similarly, SOD levels in groups G4a and G4bwere higher than in group G2, although the differencewas not statistically significant (p > 0.05). SOD levels werehigher, but not significantly so, in group G3a than in groupG4a (p > 0.05), but values for group G3b were significantly

higher than those for group G4b (p < 0.05). As for tissueMDA level, SOD levels were better in the groups treatedwith melatonin (Fig. 2).

3.1.3. GSH-Px levels

Spinal cord levels of GSH-Px were significantly lower ingroup G2 than in group G1 (p < 0.01). Groups G3a andG3b had higher GSH-Px levels than group G2; the differ-ence was significant for group G3b (p < 0.01) but not forgroup G3a (p > 0.05). Groups G4a and G4b had higher,although not significantly so, GSH-Px levels than groupG2 (p > 0.05). A non-significant difference in GSH-Px levelwas found between between G3a and G4a, and betweenG3b and G4b (p > 0.05) (Fig. 3).

F.S. Erol et al. / Journal of Clinical Neuroscience 15 (2008) 784–790 787

3.2. Histopathological investigation findings

Necrosis was found to be significantly prevented ingroups G3a and G3b (p < 0.01). Melatonin was signifi-cantly more effective than octreotide in terms of reducingnecrosis (p < 0.01).

Very severe degeneration was observed in group G2(Fig. 4). Degeneration was found to be significantly pre-vented in groups G3a, G3b, G4a and G4b (p < 0.01). Ingroup G3b, levels of degeneration, necrosis and edemawere very similar to control levels (Fig. 5).

Edema was significantly less severe in groups G3a, G3b,G4a and G4b than in group G2 (p < 0.001). In terms ofprevention of degeneration and edema, melatonin wasfound to be significantly more effective than octreotide in

Fig. 4. Histological section of spinal cord from a group G2 rat, showingsevere congestion, edema and neuronal degeneration (hematoxylin andeosin, � 400).

Fig. 5. Histological section of spinal cord from a group G3b rat(melatonin treatment over a 10-day period), showing prominent reductionin edema and congestion, and prevention of degeneration and necrosis(hematoxylin and eosin, � 400).

the early stages after injury (p < 0.01); however, there wasno difference between melatonin and octreotide in the latestages after injury (p > 0.05).

Congestion was minimal in G3a, G3b, G4a and G4b(p < 0.01), and no statistically significant difference was ob-served between the melatonin and octreotide groups(p > 0.05).

Histopathological data are summarized in Table 1.

4. Discussion

Traumatic and ischemic injuries to the central nervoussystem, including the spinal cord, cause tissue damagethrough both direct (primary) and indirect (secondary)mechanisms. Secondary injury is caused by the activationof endogenous substances. Acute inflammatory responsesat the site of injury and spinal cord hemorrhage with re-lease of iron and hemoproteins cause generation of reactiveoxygen species (ROS) and cytotoxic edema, which in turncontribute to lipid peroxidation and ischemia.10 Neuro-genic shock, together with the increase of monoamines,promotes ischemia, which increases the amount of extracel-lular glutamate.11 Glutamate activates the NMDA recep-tor, which promotes calcium and sodium ion influx. Also,voltage-gated calcium influx contributes to a decrease inextracellular calcium levels.12 Subsequently, the lysosomalphospholipase A released acts upon the cell membrane.Free fatty acids – mainly arachidonic acid (AA) – are re-leased. The AA is metabolized to eicosanoids (leukotrienesare formed by the action of lipo-oxygenase and prostaglan-dins D, E, F, tromboxane, and prostacyclin are formed bythe action of cyclo-oxygenase).13,14 This leads to tissue ede-ma and inhibits membrane-dependant Na-K-ATPase,which is responsible for blood flow, clotting mechanisms,and radical reactions.15 This, in turn, with the help of thecalcium influx, induces vasospasm and ischemia.15 Like-wise, protein kinase C activation promotes neurofilamentdegradation, which contributes to lipid peroxidation, theextent of which can be assessed using MDA levels.16 Inaddition to the uncoupling of oxidative phosphorylation,anaerobic glycolysis, ATP store depletion, and hypoxiaalso facilitate the development of ischemia.17

The spinal cord and brain are particularly vulnerable tofree radical oxidation following hypoxic or traumatic insultbecause of their high lipid content and poor iron-bindingcapacity. Anti-inflammatory10 and/or immunosuppressivedrugs,18 phospholipase inhibitors, cyclo-oxygenase/lipoxy-genase/mixed lipoxygenase-cyclo-oxygenase inhibitors,thromboxane synthetase, thromboxane, and leucotrienereceptor antagonists,13,14 ROS scavengers/antioxi-dants,17,19 biological enzymes,14,17 vitamins,20,21 seleniumcations,22 ubiquinole,21 glucose depletion,22 spinal cordblood flow restoration,23 hyperbaric oxygen therapy,24

hypothermia,25 epidural cord cooling,26 methylpredniso-lone,19,20,27,28 dextromethorphan,28 etomidate,29 hypera-tum perforatum extract,30 resveratrol,19 protein synthesisinhibitor,31 magnesium,32 lipoic acid,33 calpain inhibitor,34

Table 1Values of histopathological parameters (mean ± SD). See text for description of histological analysis

Groups Necrosis Degeneration Edema Congestion

Control (G1) 1.01 ± 0.1 1.02 ± 0.2 1.94 ± 0.5 1.95 ± 0.15Injury (G2) 4.57 ± 0.43 4.52 ± 0.46 4.85 ± 0.19 4.85 ± 0.16Injury + Melatonin-1 day (G3a) 2.28 ± 0.48 2.07 ± 0.37 2.14 ± 0.37 2.27 ± 0.53Injury + Octreotide-1 day (G4a) 4.14 ± 0.37 2.64 ± 0.33 2.44 ± 0.39 2.04 ± 0.51Injury + Melatonin-10 day (G3b) 1.73 ± 0.40 1.71 ± 0.48 1.74 ± 0.51 1.54 ± 0.51Injury + Octreotide-10 day (G4b) 3.00 ± 0.57 2.02 ± 0.53 1.72 ± 0.42 1.74 ± 0.40

788 F.S. Erol et al. / Journal of Clinical Neuroscience 15 (2008) 784–790

adenosine,35 opiate antagonists,14 and calcium channelantagonists,36 have been trialed as treatments for SCI,and found promising. Despite the high concentrations ofmonoamines on SCI, the use of a- and b-catecholamineantagonists has not been useful in clinical practice.23

Melatonin27,37–43 and octreotide44–47 are – known tohave antiproliferative, anti-ischemic, antioxidant and antie-dema effects, but to the best of our knowledge there is noprior study in which the effects of these two agents havebeen compared in a model of SCI. In our study the antie-dema, anticongestion, antidegeneration and antinecrosiseffects of these two drugs were assessed histopathologically.For both drugs, the antilipid peroxidation effects protectedcell membrane integrity, maintained cellular ion homeosta-sis and in turn decreased the edema formation.

Celebi et al.48 reported that octreotide inhibited leuco-triene biosynthesis, suppressed inflammatory responseand scavenged free radicals via oxygen radical metabolismregulation; in turn, retinal ischemia-reperfusion damagewas diminished. Octreotide was found to directly preventsuperoxide release from monocytes. It was also found todirectly decrease polymorphonuclear leucocyte cell infil-tration, thus eventually decreasing the free radical releaseof these cells indirectly.49 The effects of octreotide aremediated via specific cell receptors. Kusteter and col-leagues investigated the effects of octreotide against ische-mia-reperfusion injury in rat liver. In that study, theantioxidant effect of octreotide was claimed to be due toit having one sulfhydryl group and the capacity to induceother free radical scavenging systems.45 Octreotide hasbeen shown to protect cells by directly inhibiting leucocytefunction, regulating free oxygen radical metabolism,strongly inhibiting degranulation and release of enzymesfrom neutrophils, and decreasing superoxide anion releasefrom monocytes.49 Octreotide is known to have an antili-pid peroxidation effect.47 Furthermore, the protective ef-fects of octreotide in organ injuries have been observedin many animal experimental models.45 Our biochemicaland histopathological results support the findings in thesestudies. In our study, in group G4 octreotide was found tolower tissue MDA levels and increase SOD and GSH-Pxlevels, similar to what has previously been observed inother systemic organs such as the liver, pancreas, esopha-gus and retina. However, in the present study octreotidedid not have a significant effect on MDA levels when gi-ven immediately after injury, whereas the effect was signif-icant when given over a 10-day period following injury, In

contrast to our findings, octreotide has been previouslyfound to lower MDA levels significantly, even when givenon the first day following injury.48 In our study, octreotidehad no significant effect on SOD or GSH-Px levels duringeither the early or late stages after injury. It seems likely,however, that a significant effect could be produced byincreasing the dose of octreotide.

In accord with our biochemical findings, our histologicalobservations revealed that octreotide treatment producedbenefits with respect to neuron degeneration, edema andcongestion. In previous animal experimental studies, octre-otide has been shown to protect against organ injury.44–47

Chen at al.50 reported that octreotide diminished edema,necrosis and hemorrhage following pancreatitis. Octreoidehas also been found to be more effective than vitamin C inthe prevention of edema and necrosis after intestinalobstruction produced experimentally in rats.51 Twentydays of octreotide treatment was found to significantly re-duce edema and fibrosis in esophageal corrosive substanceinjury.44 Likewise, we observed that 10 days of octreotidetherapy significantly prevented necrosis, degeneration, ede-ma and congestion. We can see the positive effects of octre-otide on the spinal cord, which has previously been used inmany other systems and tissues as well. Drugs may diffusemore slowly into the spinal cord relative to other organstherefore in order to obtain more significant results, thedose and the infusion time of octreotide could be increased.In our experimental model, octreotide was shown to pre-vent necrosis, degeneration, and edema, which are the mostimportant targets in the treatment of SCI. However, theseeffects have yet to be shown in humans. We believe thatsimilar results could also be obtained in the human spinalcord, since octreotide has been shown to be histopatholog-ically and biochemically effective for other organs inhumans.

Melatonin is a very potent free radical scavenger.37–43

Athough it also neutralizes free radicals, its most importantfunction is activating the antioxidant enzymes that makeup the enzymatic defense system.43 It induces the activitiesof SOD, GSH-P, glutathione reductase and glucose–6-phosphate dehydrogenase.40 It has also been shown thatmelatonin reduces the activity of myeloperoxidase andthiobarbituric acid reactive species, which are importantin increasing the extent of SCI, thus facilitating the recov-ery of SCI.38 As mentioned, melatonin also behaves as a di-rect antioxidant by reacting with –OH radicals via a non-enzymatic mechanism.39 This interaction reportedly does

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not involve any membrane receptor ligand in the radicalscavenging process. For this reason, melatonin is a morepowerful antioxidant than other antioxidants (it is fivetimes more potent than glutathione and 15 times more po-tent than mannitol).28 In accord with reports in the litera-ture, in our study melatonin was found to be effective in theprevention of SCI. This effect was more pronounced interms of MDA, SOD, GSH-Px values when melatoninwas administered immediately after injury. The effects ofmelatonin in decreasing tissue MDA levels were found tobe statistically significant during the early or late stagesafter trauma. However, melatonin significantly increasedSOD and GSH-Px only when administered over a 10-dayperiod. In one previous study, 4 weeks of melatonin ther-apy for oxidative injury produced by ochratoxin in rat liverand kidneys was found to be effective in both decreasingMDA levels and increasing SOD and GSH-Px levels.52 Inanother study involving diabetic rats, melatonin was ob-served to decrease MDA levels after 6 weeks of therapy.43

Likewise, in another SCI experimental model, melatoninwas found to significantly increase SOD and GSH-Px levelseven at the end of the day following injury.42 The presentand other studies in the literature show that melatoninhas a more pronounced effect in the early stages after in-jury. In our histopathological investigations, melatoninproduced improvements in groups G3a and G3b relativeto group G2. Both melatonin treatment regimens signifi-cantly decreased necrosis, degeneration, edema and conges-tion. Axonal changes, axoplasmic edema, neurofilaments,sparse vasculature and huge and prominent cytoplasmicvacuoles in the white matter have been observed in exper-imental trauma models.27 In that study, no gray matterchanges were observed in the melatonin-treated groups.Only limited neuronal changes and slight or moderateintracytoplasmic and mitochondrial damage were ob-served.27 Fujimoto and colleagues found that melatonindecreased cyst formation and edema in an experimentalmodel of SCI.38 Melatonin has also been shown to contrib-ute to the tissue healing by reducing edema and inflamma-tion via prevention of adhesion molecule production andleucocyte adhesion to endothelial cells.53 Consistent withall of these findings, we found that melatonin had positiveeffects on the histopathological recovery processes, particu-lary edema and congestion.

5. Conclusion

In this study we observed that both melatonin and octre-otide had biochemical and histopathological benefits in anSCI model. We found that melatonin produced a morepronounced beneficial effect, which is consistent with datain the literature. Our biochemical and histopathologicalfindings correlated well. For this reason, we believe thatmelatonin and octreotide, which have the potential toupregulate antioxidant defense systems, may be beneficialin patients who sustain SCI.

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