Correlation Between Attenuation of Posttraumatic Spinal Cord Ischemia and Preservation of Tissue Vitamin E by the 21-Aminosteroid U74006F: Evidence for anIn VivoAntioxidant Mechanism

Abstract

In the present study, the ability of U74006F, the 21-aminosteroid inhibitor of lipid peroxidation, to attenuate posttraumatic spinal cord ischemia has been examined in cats following a moderately severe compression injury. Moreover, in an attempt to assess whether U74006F is affecting in vivo posttraumatic lipid peroxidation, the effect of the compound on injury-induced spinal tissue vitamin E depletion was also studied. Following an initial 10 min postinjury hyperperfusion (+45%), spinal cord blood flow (SCBF) returned to the preinjury level at 30 min before entering a phase of progressive hypoperfusion, which reached -42.0 +/- 4.5% by 4 h postinjury in the vehicle-treated animals. In animals that received 30 min postinjury U74006F i.v. doses of 1.0, 3.0, or 10 mg/kg (plus 0.5, 1.5, and 5.0 mg/kg maintenance doses at 2.5 h.), the SCBF decline was reduced to -23.1%, -22.9%, and -26.1%, respectively (p less than 0.05 vs. vehicle at all three doses). A 0.3 mg/kg dose did not reduce the posttraumatic fall in SCBF. In vehicle-treated cats, the vitamin E content of the injured cord segment was reduced by 78.9% at 4 h postinjury in comparison to cord samples from uninjured vehicle-treated cats. In contrast, the same doses of U74006F (1.0, 3.0, and 10 mg/kg) that attenuated posttraumatic ischemia also significantly reduced the depletion of cord vitamin E. The lowest U74006F dosage (0.3 mg/kg), which failed to affect posttraumatic ischemia development, also had no effect on spinal cord vitamin E content.(ABSTRACT TRUNCATED AT 250 WORDS)

Benefit of vitamin E, riluzole, and gababapentin in a transgenic model of familial amyotrophic lateral sclerosis

“…Thus, vitamin E depletion is an indication of free-radical flux in tissues and of the degree to which membranes are placed under oxidative stress. This has been shown previously in models of acute spinal cord injury [42] and focal cerebral ischemia [43] in which there occurs a rapid, [17]. Since mitochondria sequester intracellular calcium, a mitochondrial defect could cause loss of calcium homeostasis either directly through a failure to sequester calcium or indirectly due to an energy deficit [15, 171.…”

Antioxidant Therapies for Acute Spinal Cord Injury

“…As already mentioned, acute spinal cord compression injury in cats results in a rapid depletion of endogenous tissue vit E levels by 80% below the levels in noninjured spinal tissue by 4 h postinjury [64,65], due to its rapid consumption during intense post-SCI LP reactions. On the other hand, high-dose oral vit E supplementation for 5 days prior to SCI acts to attenuate the progressive posttraumatic decrease in white matter SCBF [58] together with a significant enhancement in hind-limb motor function compared to non-vit E supplemented animals [66].…”

Inhibition of Lipid Peroxidation Restores Impaired Vascular Endothelial Growth Factor Expression and Stimulates Wound Healing and Angiogenesis in the Genetically Diabetic Mouse

“…The release of oxygen radicals by adhered activated leukocytes causes additional damage because more leukocytes are attracted and the process is amplified (16). Under normal conditions, the generation of free radicals is counterbalanced by the presence of adequate endogenous antioxidant defenses (17), but when the generation of free radicals exceeds the capacity of the defenses, these highly active radicals may produce structural changes that may contribute to reversible or irreversible cell injury. Oxygen radicals cause tissue damage by lipid peroxidation of cellular and organelle membranes, disruption of the intracellular matrix, and alteration of important protein enzymatic processes (16,18).…”