Monstrey S J, Mullick P, Narayanan K, Ramasastry S S
Department of Plastic Surgery, University of Pittsburgh, School of Medicine, PA, USA.
Ann Plast Surg. 1997 Feb;38(2):163-8. doi: 10.1097/00000637-199702000-00011.
The role of hyperbaric oxygen (HBO) therapy in free radical-mediated tissue injury is not clear. HBO has been shown to enhance the antioxidative defense mechanisms in some animal studies, but HBO has also been reported to increase the production of oxygen free radicals. To investigate this controversy, we studied the effect of HBO in a doxorubicin (Adriamycin) extravasation model, because the cytotoxic activity of doxorubicin is partly related to its quinone structure, which leads to the formation of cytotoxic oxygen intermediates. Fifty-four Sprague-Dawley rats underwent injection of 0.3 ml doxorubicin solution (2 mg per milliliter) intradermally on both flanks as described by Rudolph and colleagues. 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 ulcers and the surrounding area of alopecia in group I (+HBO) were significantly larger than in group II (-HBO): 112.2 mm2 vs. 42.8 mm2 (p < 0.01) and 1,132.2 mm2 vs. 364.8 mm2 (p < 0.005). Biochemical analysis of the biopsied skin ulcers, to measure the parameters of oxygen free radical production, indicated (similar) low levels of xanthine oxidase for both groups. However, significantly elevated levels of malonyldialdehyde (MDA), indirect evidence of free radical production, was observed in group I (+HBO) in comparison with group II (-HBO): 36.58 vs. 5.84 ng per minute per milligram protein (p < 0.001), which might indicate free radical-induced cellular injury. It is concluded that in this animal study the cytotoxicity of doxorubicin is potentiated by HBO therapy. The elevated levels of MDA suggest a direct additive cytotoxic effect by increased membrane lipid peroxidation. HBO therapy, therefore, might be deleterious in the early (preulcer) stage of doxorubicin extravasation.
高压氧（HBO）疗法在自由基介导的组织损伤中的作用尚不清楚。在一些动物研究中，HBO已被证明可增强抗氧化防御机制，但也有报道称HBO会增加氧自由基的产生。为了研究这一争议，我们在阿霉素外渗模型中研究了HBO的作用，因为阿霉素的细胞毒性活性部分与其醌结构有关，这会导致细胞毒性氧中间体的形成。按照鲁道夫及其同事的描述，对54只Sprague-Dawley大鼠双侧皮内注射0.3 ml阿霉素溶液（每毫升2 mg）。第一组（N = 28）在注射前3天和注射后7天接受HBO治疗（2 ATA下2小时）。第二组（N = 26）未接受HBO治疗。在第2、3和5周时，第一组（+HBO）溃疡的大小和周围脱发区域明显大于第二组（-HBO）：分别为112.2平方毫米对42.8平方毫米（p < 0.01）和1132.2平方毫米对364.8平方毫米（p < 0.005）。对活检的皮肤溃疡进行生化分析以测量氧自由基产生的参数，结果显示两组黄嘌呤氧化酶水平（相似）较低。然而，与第二组（-HBO）相比，第一组（+HBO）中丙二醛（MDA）水平显著升高，MDA是自由基产生的间接证据：每分钟每毫克蛋白质36.58对5.84 ng（p < 0.001），这可能表明自由基诱导的细胞损伤。得出的结论是，在这项动物研究中，HBO疗法增强了阿霉素的细胞毒性。MDA水平升高表明膜脂质过氧化增加产生了直接的相加细胞毒性作用。因此，HBO疗法在阿霉素外渗的早期（溃疡前期）阶段可能有害。
