Correlation between attenuation of posttraumatic spinal cord ischemia and preservation of tissue vitamin E by the 21-aminosteroid U74006F: evidence for an in vivo antioxidant mechanism.
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)
Hall
E D
ED
Central Nervous System Diseases Research Unit, Upjohn Company, Kalamazoo, Michigan.
Yonkers
P A
PA
Horan
K L
KL
Braughler
J M
JM
D000818:Animals; D002415:Cats; D005260:Female; D007511:Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008054:Lipid Peroxides / Q000037:antagonists & inhibitors*; D011281:Pregnatrienes / Q000008:administration & dosage / Q000494:pharmacology*; D012039:Regional Blood Flow; D013116:Spinal Cord / Q000098:blood supply* / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D013997:Time Factors; D014810:Vitamin E / Q000032:analysis
D008054:Lipid Peroxides; D011281:Pregnatrienes; D014810:Vitamin E; C053355:tirilazad