Effect of mexiletine on lipid peroxidation and early ultrastructural findings in experimental spinal cord injury

Kaptanoğlu, Erkan; Caner, Hh; Hs, Sürücü; Akbıyık, Filiz

doi:10.3171/spi.1999.91.2.0200

Cited by 36 publications

(25 citation statements)

References 30 publications

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“…However, at the end of the study the significantly lower levels of MDA in the MP+melatonin combined treatment group in comparison with the other treatment groups may be the result of additive or synergistic effects of different antioxidative mechanisms. This effect might be insignifi-cant for preventing the pathological process of the injury since maximum tissue destruction takes place immediately and continues for 24h after the injury [13,17]. Neurobehavioral, ultrastructural, and electrophysiological results of our study also support this opinion.…”

Section: Discussionsupporting

confidence: 79%

Effect of combined treatment with melatonin and methylprednisolone on neurological recovery after experimental spinal cord injury

et al. 2004

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Spinal cord injury (SCI) results in the loss of function below the lesion. Secondary injury following the primary impact includes a number of biochemical and cellular alterations leading to tissue necrosis and cell death. Methylprednisolone (MP), by reducing edema and protecting the cell membrane against peroxidation, is the only pharmacological agent with a proven clinically beneficial effect on SCI. Melatonin, known as a free radical scavenger, has been shown to have an effect on lipid peroxidation following experimental SCI. The purpose of this study was to examine the effect of MP and melatonin on neurological, ultrastructural, and electrophysiological recovery. Female albino rats weighing 200-250 g were randomized into five groups of 18 rats each and six rats for the control group. Weight-drop trauma was performed for each group and a 30-mg/kg single dose of MP for rats in group 1, a 10-mg/kg single dose of melatonin for rats in group 2, and MP and melatonin in the same doses for rats in group 3 were administered immediately after trauma. The rats in group 4 were the vehicle group (treated with ethanol) and group 5 was the trauma group. The motor and somatosensory evoked potentials were recorded at the 4th hour, the 24th hour, and on the 10th day of the study for six rats in each group. Posttraumatic neurological recovery was recorded for 10 days using "motor function score" and inclined plane test. After electrophysiological study the rats were terminated for an analysis of lipid peroxidation level of the injured site of the spinal cord. Electron microscopic studies were performed to determine the effects of melatonin, MP, and the combined treatment with MP and melatonin on axons, neurons, myelin, nucleus, and intracytoplasmic edema. The groups treated with MP, melatonin, and a combination of both had significantly enhanced electrophysiological, biochemical, and neurological recovery and also showed better ultrastructural findings than the trauma and vehicle groups. Although combined treatment was significantly more effective on lipid peroxidation than melatonin or MP treatments alone, at the 10th day, neurobehavioral, electrophysiological, and ultrastructural recovery were at the same level. In conclusion, MP, melatonin, and MP and melatonin combined treatment modalities improved functional recovery at the same level. Future studies involving different doses of melatonin and different dose combinations with MP could promise better results since each drug has a different antioxidative mechanism of action.

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Section: Discussionsupporting

confidence: 79%

Effect of combined treatment with melatonin and methylprednisolone on neurological recovery after experimental spinal cord injury

et al. 2004

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“…Further, the ROS level measured in the control-uninjured group in our study is comparable with that of healthy tissue of other e ective in vivo models. 20,21 Our measurements also indicate that our in vitro experimental condition was su cient to sustain the functional integrity of the extracted tissue. For example, electrophysiological recording, using double sucrose-gap chamber, showed that the isolated spinal cord tissue, when no deliberate compression was performed, was functionally competent by the end of the maximal experimental period (4 h) (Figure 2).…”

Section: Discussionmentioning

confidence: 59%

“…20,21,32 For example, the LPO values range from about 6 ± 10 nmol/100 mg 20,21 to 158 nmol/100 mg 32 in the control. One possible explanation of such a phenomenon is the inability to standardize the experimental condition in these in vivo studies.…”

Section: Discussionmentioning

confidence: 95%

“…This level is also comparable with other in vivo studies. 20,21 Secondly, a standard compression produced an LPO level of 21.23+3.22 nmol/100 mg at 1 h after injury, a 200% increase from the control-uninjured group (P50.01, n=5). Thirdly, a treatment of either ascorbic acid or hypothermia to the compressed cords reduced the lipid peroxidation level of 17.96+3.0 nmol/100 mg and 16.43+2.89 nmol/100 mg; both are signi®cantly lower than those measured in the compression-untreated group (P50.01, n=5).…”

Section: Lipid Peroxidationmentioning

confidence: 91%

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The increase of reactive oxygen species and their inhibition in an isolated guinea pig spinal cord compression model

Luo

Robinson

et al. 2002

Spinal Cord

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Study design:In vitro studies using isolated guinea pig spinal cord. Objectives: To develop an alternative model using isolated guinea pig spinal cord, which can be used to screen antioxidants for in vivo SCI treatment. Setting: Department of Basic Medical Sciences, Purdue University, West Lafayette, Indiana, USA. Methods: The compression injury was induced by a constant-displacement of 5-s compression of spinal cord using a modi®ed forceps possessing a spacer. Reactive oxygen species (ROS) were evaluated using three distinct methods:¯uorescence microscopy, lipid peroxidation assay, and¯ow cytometry. Results: The injury-mediated ROS increases are comparable with other in vivo studies and consistent with our previous observation using a similar injury model and measured with electrophysiological and anatomical technique. Further, ascorbic acid, hypothermia, or the combination of both signi®cantly suppressed superoxide and lipid peroxidation. The combination treatment was the most e ective when compared with ascorbic acid or hypothermia alone. Conclusion: This in vitro model has the advantage of replicating some of the in vivo conditions while gaining the ability to control the experimental conditions. This in vitro model is suitable to study the mechanisms of ROS generation and degradation and can also be used to critically evaluate the e ective suppressor of ROS in the contents of spinal cord traumatic injury.

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“…There have been a number of studies performed in an attempt to identify the pathophysiological mechanisms occurring after traumatic SCI. [12][13][14][15] Lipid peroxidation is one of the main pathological mechanisms involved in secondary damage after a SCI. The primary autodestructive event is started by the hydrolysis of fatty acids from membrane phospholipids, leading to cellular damage.…”

Section: Discussionmentioning

confidence: 99%

Effectiveness of FK506 on lipid peroxidation in the spinal cord following experimental traumatic injury

et al. 2004

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Study design: An in vivo study in Wistar albino rats with injured spinal cord. Setting Department of Neurosurgery, Biochemistry and Pathology, Gazi University, Ankara, Turkey. Objectives: The aim of this study was to investigate and compare the effects of FK506 an immunosupressive agent with methylprednisolone (MP) on lipid peroxidation (LP) in injured spinal cord tissue. Method: A total of 28 adult healthy Wistar albino rats were subjected to traumatic spinal cord injuries (SCI) by using an aneurysmal clip compression technique, and they were divided into four groups. The G1 group (n ¼ 8) received FK506 (1 mg/kg); the G2 group (n ¼ 8) received FK506 (1 mg/kg) and MP (30 mg/kg); the G3 group (n ¼ 6) received only MP (30 mg/kg); and the G4 group (n ¼ 6) received no medication. The injured spinal cord tissue was studied by means of lipid peroxides, malondialdehyde (MDA), with thiobarbituric acid reaction and additionally the FK506 (G1); the MP (G3) groups were studied for histopathologic alterations 72 h after SCI with eight separate animals. Results: Although LP values of G1, G2, G3 showed no statistical difference between intergroup analyses (P ¼ 0.547), a histopathological examination revealed that in the group that received MP, the oedema pattern was more significant than the group that received FK506. Another interesting finding was the presence of polymorphonuclear leucocytes in the MP group, whereas no infiltration was found in the FK506 group. Conclusion: Analysis of the results indicated that FK506 is a valuable pharmacological agent that could be used to decrease the LP and polymorphonuclear leucocyte infiltration and inflamatory reactions in the injured spinal cord tissue.Spinal Cord (2005) 43, 22-26.

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Effect of mexiletine on lipid peroxidation and early ultrastructural findings in experimental spinal cord injury

Cited by 36 publications

References 30 publications

Effect of combined treatment with melatonin and methylprednisolone on neurological recovery after experimental spinal cord injury

Effect of combined treatment with melatonin and methylprednisolone on neurological recovery after experimental spinal cord injury

The increase of reactive oxygen species and their inhibition in an isolated guinea pig spinal cord compression model

Effectiveness of FK506 on lipid peroxidation in the spinal cord following experimental traumatic injury

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