The tripeptide phenylalanine-(D) glutamate-(D) glycine modulates leukocyte infiltration and oxidative damage in rat injured spinal cord.
The tripeptide, phenylalanine-glutamate-glycine (FEG) and its d-isomeric form phenylalanine-(D) glutamate-(D) glycine (feG), derived from submandibular gland peptide-T, significantly reduce the allergic inflammatory response and leukocyte trafficking and neutrophil migration into intestine, heart and lungs. Due to these actions, we hypothesized that feG would attenuate the early inflammatory response to spinal cord injury, reduce free radical production and improve neurological outcomes, like other leukocyte-limiting strategies we have used previously. We tested this using a clip compression model of spinal cord injury in rats. Following spinal cord injury at the 4th thoracic cord segment, we quantified leukocyte infiltration, free radical formation and oxidative damage at the lesion site after feG or control peptide phenylalanine-(D) aspartate-(D) glycine treatment. In rats treated with feG at 2 and 12 h, or 6 and 12 h after spinal cord injury, mean myeloperoxidase activity and ED-1 expression were significantly lower ( approximately 40%) than in controls at 24 h. Free radical formation generated in injured spinal cord was detected using 2',7'-dichlorofluorescin-diacetate as a fluorescent probe. Free radical production in the injured cord increased significantly after spinal cord injury and feG treatment significantly reduced this free radical production. Oxidative enzymes, lipid peroxidation and cell death were also significantly ( approximately 40%), gp91 ( approximately 30%), thiobarbituric acid reactive substance levels ( approximately 35%), 4-hydroxynonenal-bound protein ( approximately 35%) and caspase-3 ( approximately 32%). Early administration of feG decreases infiltration of inflammatory cells into the injured spinal cord and intraspinal free radical formation, thereby reducing oxidative damage and secondary cell death after spinal cord injury.
Spinal Cord Injury Team, Laboratory of Spinal Cord Injury, BioTherapeutics Research Group, Robarts Research Institute, 100 Perth Drive, London, Ontario, Canada N6A 5K8.
F
F
Bao
S M
SM
John
Y
Y
Chen
R D
RD
Mathison
L C
LC
Weaver
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000502:physiology*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004334:Drug Administration Schedule; D053331:Ectodysplasins; D005260:Female; D005456:Fluorescent Dyes; D005609:Free Radicals / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008565:Membrane Proteins / Q000378:metabolism; D009410:Nerve Degeneration / Q000188:drug therapy / Q000378:metabolism* / Q000517:prevention & control; D009842:Oligopeptides / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D013117:Spinal Cord Compression / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D013997:Time Factors; D048069:Tumor Necrosis Factors / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D053331:Ectodysplasins; D005456:Fluorescent Dyes; D005609:Free Radicals; D008565:Membrane Proteins; D009842:Oligopeptides; D017392:Thiobarbituric Acid Reactive Substances; D048069:Tumor Necrosis Factors; C114891:tripeptide FEG; D009195:Peroxidase; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases