Effect of glutathione augmentation on lipid peroxidation after spinal cord injury.
Lipid peroxidation (LPO) is considered a major factor in damage spread after spinal cord injury (SCI). Therapies that limit LPO after SCI have demonstrated some utility in clinical trials, but more effective treatments are needed. In the present study the effects of augmenting SC levels of the endogenous antioxidant glutathione (GSH) on LPO after SCI were studied in a rat contusion injury model. A significant decrease in GSH occurred 1h after SCI which was paralleled by increases of 123% in malondialdehyde (MDA) and >500% in the 4-hydroxyalkenals (4-HA's), two LPO products. SC irrigation with gamma-glutamylcysteine (GC) preserved GSH and reduced 4-HA's below naive levels but had no effect on MDA. By 24 h after SCI, MDA returned to naive levels but 4-HA's were still elevated. Once again, GC treatment reduced 4-HA's. 4-HA's are much more reactive than MDA and are considered among the most toxic LPO products. These results suggest that (1) conditions after SCI may favor particular branches of the LPO pathway leading to differential LPO product levels, (2) MDA measurement is not by itself an adequate test for the presence or magnitude of LPO after SCI, (3) binding of GSH to 4-HA's may be an important mechanism by which the GSH system confers protection against LPO after SCI, and (4) SC GSH can be augmented after trauma by local irrigation with GC. These results also suggest that GSH augmentation may be an effective strategy for curtailment of LPO-mediated damage in acute phase SCI.
Lucas
Jen Hill
JH
Department of Physiology and Cell Biology, The Ohio State University College of Medicine, Columbus, Ohio 43210, USA. lucas.72@osu.edu
Wheeler
Debra G
DG
Guan
Zhen
Z
Suntres
Zacharias
Z
Stokes
Bradford T
BT
D000208:Acute Disease; D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D005260:Female; D005978:Glutathione / Q000378:metabolism / Q000494:pharmacology*; D019803:Glutathione Disulfide / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D015918:Infusion Pumps, Implantable; D015227:Lipid Peroxidation / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000378:metabolism*
D000447:Aldehydes; D000975:Antioxidants; D005982:Glutathione Transferase; D005978:Glutathione; C027576:4-hydroxy-2-nonenal; D019803:Glutathione Disulfide