Promoting glutathione synthesis after spinal cord trauma decreases secondary damage and promotes retention of function

Kamencic, Huse; Griebel, Robert; Lyon, Andrew W.; Paterson, Phyllis G.; Juurlink, Bernhard H.J.

doi:10.1096/fj.00-0228com

Cited by 96 publications

(59 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Oxidative stress consumes GSH either by oxidation or through the formation of adducts with electrophilic Effect of 2-amino-5-phosphonovaleric acid after spinal cord trauma M Vural et al compounds and metals. 2 Our results indicated that APV treatment almost restored the decreased GSH level after SCI in a dose-dependent manner. The increase after treatment is more prominent in higher doses but this increase was not sufficient to improve MDA levels.…”

Section: Parameters Of Oxidative Stresssupporting

confidence: 53%

“…Thus, increased MDA and protein carbonyl levels and loss or oxidation of GSH, and decreased SOD and catalase activities provide physiologically relevant estimates of oxidative stress in tissues even in the neuronal system. Kamencic et al 2 reported that after a SCI, the GSH content of the site of injury and adjacent tissue was reduced to less than half of the normal within 1 h, and over the next 48 h, there was a further decrease in the GSH level of the spinal cord. Oxidative stress consumes GSH either by oxidation or through the formation of adducts with electrophilic Effect of 2-amino-5-phosphonovaleric acid after spinal cord trauma M Vural et al compounds and metals.…”

Section: Parameters Of Oxidative Stressmentioning

confidence: 99%

“…Antioxidant enzyme levels were found unchanged at 4 h after trauma. [2][3][4] In recent years, evidence supporting the involvement of excitatory amino acids in the development of secondary pathology after SCI has been reported. Glutamate is an excitatory neurotransmitter to the central nervous system; an increase in released glutamate after trauma is toxic to neuronal cells.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

NMDA receptor blockage with 2-amino-5-phosphonovaleric acid improves oxidative stress after spinal cord trauma in rats

et al. 2009

View full text Add to dashboard Cite

Study design: 2-amino-5-phosphonovaleric acid (APV) is an N-methyl-D-aspartate (NMDA) receptor blocker and has neuroprotective properties. This study is aimed at evaluating the effect of APV treatment on oxidative status after spinal cord injury (SCI). Methods: The experiment was carried out on the following five groups: Group1: sham operated, non-traumatized; Group2: with injured spinal cord, no treatment; Group3: with SCI, injected with 100 mg kg À1 APV; Group4: with SCI, injected with 200 mg kg À1 APV; and Group5: with SCI, injected with 400 mg kg À1 APV. SCI was inflicted by epidural compression with a cerebral vascular clip after T9-11 laminectomy. The experiments were completed after 12 h of trauma. Spinal cords were excised for evaluation of superoxide dismutase (SOD), catalase, reduced glutathione (GSH) and malonyldialdehyde (MDA) levels. Results: After SCI, SOD and GSH levels decreased and the MDA level increased significantly. APV treatment decreased the MDA level and increased SOD, catalase and GSH levels. The maximum decrease in MDA was detected in the group treated with 100 mg kg À1 APV compared with the other groups. The GSH level was significantly increased in the group treated with 200 mg kg À1 APV. The SOD level was significantly increased in the group treated with 200 mg kg À1 APV. Conclusion:The results of this study have shown that APV treatment creates a dose-dependent antioxidant effect in rats with SCI and may be used for the treatment of SCIs.

show abstract

Section: Parameters Of Oxidative Stresssupporting

confidence: 53%

Section: Parameters Of Oxidative Stressmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

NMDA receptor blockage with 2-amino-5-phosphonovaleric acid improves oxidative stress after spinal cord trauma in rats

et al. 2009

View full text Add to dashboard Cite

show abstract

“…Between 24 and 48 h, significant decreases in glutathione were also observed throughout the spinal cord from spinal segments C3 to L4, suggesting that the decrease of glutathione may be a hallmark of oxidative stress that accompanies the prominent inflammatory changes after spinal cord trauma. 37 There are several chemical 38 and enzymatic 39 assays available for determination of glutathione. However, most of these assays lack sensitivity and specificity.…”

Section: Nucleusmentioning

confidence: 99%

Oxidative stress in spinal cord injury and antioxidant-based intervention

Jia

Zhu

Li³

et al. 2011

Spinal Cord

249

160

View full text Add to dashboard Cite

Study design: Literature review. Objectives: Spinal cord injury (SCI) remains a major public health issue in developed countries as well as worldwide. The pathophysiology of SCI is characterized by an initial primary injury followed by secondary deterioration. Although the etiology and pathogenesis of SCI remain to be fully understood, it has been suggested that reactive oxygen species (ROS) and oxidative stress have a significant role in the pathophysiology of SCI. Thus, alleviating oxidative stress may be an effective strategy for therapeutic intervention of SCI. The aim of this review was to describe (i) the sources of ROS as well as the major antioxidant defenses with particular attention being paid to lipid peroxidation; (ii) the biomarkers of oxidative stress in SCI and (iii) the neuroprotective effects of various compounds with antioxidative properties in animal models of SCI. Methods: PubMed, one of the most comprehensive biomedical databases, was searched from 1976-2011. All relevant papers were read by title, abstract and full-length article. Results: Oxidative stress is considered a hallmark of injury of SCI. Thus, alleviating oxidative stress may be an effective way of therapeutic intervention of SCI. Two of these agents, the glucocorticoid steroid methylprednisolone and the non-glucocorticoid 21-aminosteroid tirilazad, have been shown to possess significant antioxidant activities and improve recovery of SCI patients in clinical trials. Other promising botanical compounds and their molecular targets and mechanisms of action with regard to potential protection against SCI were also described. These include carotenoids and phenolic compounds. Conclusion: ROS and oxidative stress have a significant role in the pathophysiology of SCI. Alleviating oxidative stress is be an effective strategy for therapeutic intervention of SCI. Extensive research over the past several decades has identified numerous bioactive compounds that have antioxidative stress benefits in animal models of SCI. Thus, continued studies on bioactive compounds with ROS-scavenging capacity may lead to the development of effective antioxidant-based modalities for treating SCI in human subjects.

show abstract

“…4,5 Studies in an animal model of spinal cord compression injury have shown that survival of as little as 10% of all axons in the rat spinal cord is sufficient to support significant motor function. 6,7 Therefore, protection of even a small number of primarily undamaged axons from delayed cell death may result in a considerable difference in functional outcome for the patient.…”

Section: Introductionmentioning

confidence: 99%

Quercetin attenuates inflammatory processes after spinal cord injury in an animal model

2010

View full text Add to dashboard Cite

Objectives: We have shown earlier that administration of the flavonoid quercetin significantly contributed to recovery of motor function after spinal cord compression injury in the adult rat. Using the same animal model, we have now designed a set of experiments to test the hypothesis that quercetin attenuates oxidative stress-related inflammatory processes early after spinal cord trauma. Methods: Mid-thoracic spinal cord compression injury in adult male Wistar rats was caused by extradural application and closure of a 50 g calibrated aneurysm clip for 5 s. Myeloperoxidase (MPO) levels were determined in spinal cord tissue and serum of quercetin-treated animals and controls at 6, 12, 24 and 72 h after injury. The white blood count was followed until 72 h after injury. Results: In quercetin-treated animals, MPO activity was significantly decreased in tissue at 12 and 24 h and in serum at 6, 12 and 24 h after injury, compared with saline controls. In quercetin-treated animals, the prevalence of ED-1 and MPO positive cells was significantly lower than in saline controls. White blood count in venous blood was significantly decreased in quercetin-treated animals at 12 and 24 h after injury. Conclusion: Quercetin attenuated the recruitment of neutrophils to the site of injury. The resulting lower MPO release in the injured tissue is likely to decrease the extent of secondary injury and might at least partially explain the neuroprotective effect of the flavonoid quercetin.

show abstract

Promoting glutathione synthesis after spinal cord trauma decreases secondary damage and promotes retention of function

Cited by 96 publications

References 44 publications

NMDA receptor blockage with 2-amino-5-phosphonovaleric acid improves oxidative stress after spinal cord trauma in rats

NMDA receptor blockage with 2-amino-5-phosphonovaleric acid improves oxidative stress after spinal cord trauma in rats

Oxidative stress in spinal cord injury and antioxidant-based intervention

Quercetin attenuates inflammatory processes after spinal cord injury in an animal model

Contact Info

Product

Resources

About