Altered wound arginine metabolism by corticosterone and retinoic acid

Arginine metabolism plays an important role in many aspects of inflammation and wound healing. In this study, we tested the hypothesis that steroids and vitamin A have differential effects on arginine metabolism and thereby may provide a mechanism by which steroids impair wound healing, and vitamin A improves this impairment. Rats were treated with subcutaneous corticosterone pellets 2 days prior to wounding. Intraperitoneal injections of all-trans retinoic acid in peanut oil were administered at the same time and repeated 2 and 4 days later. Polyvinyl alcohol sponges were implanted subcutaneously through a dorsal incision. On Postwounding Days 1, 5, 10, and 15, wound fluid was recovered from the sponges and assayed for nitrite/nitrate (NOx), citrulline, arginine, and ornithine concentrations as well as arginase activity. Steroid treatment decreased the metabolism of arginine to nitric oxide in the early phase of wound healing, and retinoic acid did not change this relationship. Corticosterone also decreased metabolism of arginine to ornithine in the later wound. This depression was inhibited by concomitant administration of retinoic acid. Considering the importance of nitric oxide in host defense and ornithine as a precursor for polyamine and proline synthesis, these data provide a mechanism by which vitamin A improves wound strength, but does not improve wound infection rates in steroid-treated animals.