DELAYED REPAIR - THE ROLE OF GLUTATHIONE IN A RAT INCISIONAL WOUND MODEL

Glutathione is a low molecular weight tripeptide that is a major intra cellular antioxidant, modulates DNA synthesis, and may regulate signal transduction mechanisms, Our previous studies in rats suggested that intracellular stores of glutathione were sensitive to skin ischemia an d, therefore, may regulate the early temporal course of wound healing. A 4-cm incision was placed on a rat's back and in vivo wound strength was measured over time, Animals were depleted of glutathione using L- buthionine-(S,R)-sulfoximine (BSO), an inhibitor of the enzyme gamma-g lutamylcysteine synthetase, Some animals were treated in combination w ith allopurinol/BSO or with allopurinol alone, The data demonstrated a t 4 days that BSO treatment produced a fourfold reduction in glutathio ne (3.51 +/- 1.78) over baseline (16.15 +/- 2.18) levels and twofold r eduction (5.0 +/- 1.1) over untreated sham controls (11.1 +/- 2.3) (P < 0.05). Allopurinol provided no protection to glutathione levels. BSO treatment alone reduced wound burst strength compared to the other gr oups (P < 0.05), Allopurinol treatment enhanced wound strength over sh am controls and BSO groups at 9 days after wounding (P < 0.05). Hydrox yproline content in wounds accumulated faster by Day 4 in the BSO-trea tment groups compared to sham controls (P < 0.05), whereas the BSO-tre atment groups had lower hydroxyproline levels measured at Day 6 (P < 0 .05), These data provide the first evidence that wound healing is rela ted to the temporal course of glutathione metabolism, The effect may n ot be related to oxidant stress since allopurinol provided enhanced wo und burst strength without protecting wound glutathione levels, (C) 19 96 Academic Press, Inc.