HYPERBARIC-OXYGEN THERAPY AND FREE-RADICAL PRODUCTION - AN EXPERIMENTAL-STUDY IN DOXORUBICIN (ADRIAMYCIN) EXTRAVASATION INJURIES

The role of hyperbaric oxygen (HBO) therapy in free radical-mediated t issue injury is not clear. HBO has been shown to enhance the antioxida tive defense mechanisms in some animal studies, but HBO has also been reported to increase the production of oxygen free radicals. To invest igate this controversy, we studied the effect of HBO in a doxorubicin (Adriamycin) extravasation model, because the cytotoxic activity of do xorubicin is partly related to its quinone structure, which leads to t he formation of cytotoxic oxygen intermediates. Fifty-four Sprague-Daw ley rats underwent injection of 0.3 mi doxorubicin solution (2 mg per milliliter) intradermally on both flanks as described by Rudolph and c olleagues. Group I (N = 28) received HBO treatment (2 hours at 2 ATA) for 3 days prior to injection and 7 days postinjection. Group II (N = 26) received no HBO treatment. At 2, 3, and 5 weeks, the size of the u lcers and the surrounding area of alopecia in group I (+HBO) were sign ificantly larger than in group lI (-HBO): 112.2 mm(2) vs. 42.8 mm(2) ( p < 0.01) and 1,132.2 mm(2) vs. 364.8 mm(2) (p < 0.005). Biochemical a nalysis of the biopsied skin ulcers, to measure the parameters of oxyg en free radical production, indicated (similar) low levels of xanthine oxidase for both groups. However, significantly elevated levels of ma lonyldialdehyde (MDA), indirect evidence of free radical production, w as observed in group I (+HBO) in comparison with group II (-HBO): 36.5 8 vs. 5.84 ng per minute per milligram protein (p < 0.001), which migh t indicate free radical-induced cellular injury. It is concluded that in this animal study the cytotoxicity of doxorubicin is potentiated by H8O therapy. The elevated levels of MDA suggest a direct additive cyt otoxic effect by increased membrane lipid peroxidation. HBO therapy, t herefore, might be deleterious in the early (preulcer) stage of doxoru bicin extravasation.