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

• Published in: The FASEB journal Vol. 15; no. 1; p. 243
• Main Authors: Kamencic, H, Griebel, R W, Lyon, A W, Paterson, P G, Juurlink, B H
• Format: Journal Article
• Language: English
• Published: United States 01.01.2001
• Subjects: Animals; Behavior, Animal - drug effects; Glutathione - biosynthesis; Glutathione - metabolism; Glutathione Reductase - metabolism; Male; Oxidative Stress - drug effects; Oxidative Stress - physiology; Pyrrolidonecarboxylic Acid; Rats; Rats, Wistar; Spinal Cord - drug effects; Spinal Cord - enzymology; Spinal Cord - metabolism; Spinal Cord - physiology; Spinal Cord Compression - enzymology; Spinal Cord Compression - metabolism; Spinal Cord Compression - physiopathology; Spinal Cord Injuries - enzymology; Spinal Cord Injuries - metabolism; Spinal Cord Injuries - physiopathology; Thiazoles - pharmacology; Thiazolidines; Up-Regulation - drug effects
• ISSN: 0892-6638
• DOI: 10.1096/fj.00-0228com

The study aimed to 1) quantify oxidative stress in spinal cord after crush injury at T6, 2) determine whether the administration of the procysteine compound L-2-oxothiazolidine-4-carboxylate (OTC) would up-regulate glutathione (GSH) synthesis and decrease oxidative stress, and 3) determine whether decreased oxidative stress results in better tissue and function retention. We demonstrate that spinal cord compression (5 s with a 50 g aneurysm clip) at T6 in rats results in oxidative stress that is extensive (significant increases in oxidative stress seen at C3 and L4) and rapid in onset. Indices of oxidative stress used were GSH content, protein carbonyl content, and inactivation of glutathione reductase. Administration of OTC resulted in a marked decrease in oxidative stress associated with a sparing of white matter at T6 (16+/-1.9% retained in OTC-treated animals vs. less than 1% in saline-treated). Behavioral indices in control, saline-treated, and OTC-treated animals after 6 wk were respectively: angle board scores (59 degrees, 32 degrees, and 42 degrees ), modified Tarlov score (7, 2.4, and 4.1), and Basso-Beattie-Bresnahan score (21, 5.3, and 12.9). We conclude that administration of OTC after spinal cord trauma greatly decreases oxidative stress and allows tissue preservation, thereby enabling otherwise paraplegic animals to locomote.