Control of oxidative stress in small bowel: relevance to organ preservation.
BACKGROUND
Oxidative stress during cold small bowel (SB) storage has not been investigated because oxygen is depleted rapidly after procurement. We hypothesized that oxidative catabolism facilitated by a proven amino acid-based (AA) storage solution promotes oxidative stress; furthermore, there is an important role for antioxidant supplementation during cold storage.


METHODS
SB from Sprague-Dawley rats (n = 6 in each group) were procured according to standardized procedures involving vascular flush with modified University of Wisconsin solution and luminal treatment with an AA-based solution proven previously to aid preservation. SB were assigned randomly to the following antioxidant treatment groups: group 1, none; group 2, superoxide dismutase/catalase; group 3, 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox, a water-soluble analogue of vitamin E). Energetics, oxidative stress, electrophysiology, and histology were assessed over 24 hours at 4 degrees C.


RESULTS
The addition of Trolox in group 3 resulted in a significant reduction in malondialdehyde levels compared with all other groups throughout 24 hours of cold storage. Tissue energetics correlated well with reduced oxidative injury; over the first 12 hours, adenosine triphosphate and total adenylates were superior in tissues treated with Trolox (group 3) versus AA solution alone (group 1). Functional assessment showed relatively normal permeability in all groups, however, Trolox-treated tissues showed significantly higher short-circuit current compared with control group (17.7 vs 5.5 microA/cm(2)). Histologic integrity was improved in group 3 after 24 hours of cold storage.


CONCLUSIONS
Oxidative stress appears to be a determinant in the pathogenesis of mucosal injury during cold storage. Trolox effectively abrogates storage-related oxidative stress in SB.
Surgical-Medical Research Institute, 1074 Dentistry-Pharmacy Building, University of Alberta, Edmonton, Alberta, Canada T6G 2N8.
Payam
P
Salehi
John
J
Walker
Karen
K
Madsen
Thomas A
TA
Churchill
D000596:Amino Acids; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002839:Chromans / Q000494:pharmacology*; D004594:Electrophysiology; D004734:Energy Metabolism; D007413:Intestinal Mucosa / Q000473:pathology; D007421:Intestine, Small / Q000637:transplantation*; D008297:Male; D009926:Organ Preservation / Q000379:methods*; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley
D000596:Amino Acids; D000975:Antioxidants; D002839:Chromans; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid