Dennery P A, McDonagh A F, Spitz D R, Rodgers P A, Stevenson D K
Department of Pediatrics, Stanford University School of Medicine, CA, USA.
Free Radic Biol Med. 1995 Oct;19(4):395-404. doi: 10.1016/0891-5849(95)00032-s.
Bilirubin is a potent antioxidant in vitro. To determine whether bilirubin also is an antioxidant in vivo, we studied markers of oxidative injury in the Gunn rat model exposed to hyperoxia. Homozygous jaundiced males were mated with heterozygous nonjaundiced females to obtain both jaundiced and nonjaundiced pups within a litter. Once delivered, the pups and their mother were placed in air (21% O2) or hyperoxia (> 95% O2) for 3 d. Both jaundiced and nonjaundiced pups were removed from the chambers daily. Animals were sacrificed and blood was drawn for determination of serum bilirubin, blood thiobarbituric acid-reactive substances (TBARS) by fluorescence assay, serum hydroperoxides, and serum protein oxidation. Tissues (liver, lung, and brain) were assayed for lipid peroxides (TBARS, conjugated dienes [CD], loss of polyunsaturated fatty acid content [PUFA]). We also measured a wide range of serum antioxidants including superoxide dismutase, catalase, glutathione, vitamins A, C, and E, and uric acid. Blood TBARS were significantly decreased in the jaundiced pups compared to the nonjaundiced pups on day 3 of hyperoxia, and blood TBARS were inversely correlated to serum bilirubin on day 3 of hyperoxia (R2 +/- .89). Similar decreases in serum lipid hydroperoxides and serum protein carbonyl content were detected in the jaundiced pups as compared to their nonjaundiced littermates. Other serum antioxidants were not increased in jaundiced animals compared to nonjaundiced animals. Relative lung weight was lower in jaundiced pups exposed to hyperoxia compared to similarly exposed nonjaundiced pups, suggesting a reduction in hyperoxia-induced lung edema. We detected no significant effects of bilirubin on parameters of lipid peroxidation in solid tissues. We conclude that serum bilirubin protects against serum oxidative damage in the first days of life in neonatal Gunn rats exposed to hyperoxia. We speculate that bilirubin is a functionally important transitional antioxidant in the circulation of human neonates and that it may be involved in modulation of injury due to hyperoxia.
胆红素在体外是一种有效的抗氧化剂。为了确定胆红素在体内是否也是一种抗氧化剂，我们在暴露于高氧环境的冈恩大鼠模型中研究了氧化损伤的标志物。将纯合黄疸雄性大鼠与杂合非黄疸雌性大鼠交配，以便在同一窝中获得黄疸和非黄疸幼崽。幼崽出生后，将幼崽及其母亲置于空气中（21%氧气）或高氧环境（>95%氧气）中3天。每天从实验箱中取出黄疸和非黄疸幼崽。处死动物并取血，通过荧光测定法测定血清胆红素、血硫代巴比妥酸反应性物质（TBARS）、血清氢过氧化物和血清蛋白氧化情况。检测组织（肝脏、肺和脑）中的脂质过氧化物（TBARS、共轭二烯[CD]、多不饱和脂肪酸含量[PUFA]的损失）。我们还测量了多种血清抗氧化剂，包括超氧化物歧化酶、过氧化氢酶、谷胱甘肽、维生素A、C和E以及尿酸。在高氧暴露第3天，与非黄疸幼崽相比，黄疸幼崽的血TBARS显著降低，且在高氧暴露第3天，血TBARS与血清胆红素呈负相关（R2±0.89）。与非黄疸同窝幼崽相比，在黄疸幼崽中检测到血清脂质氢过氧化物和血清蛋白羰基含量有类似降低。与非黄疸动物相比，黄疸动物的其他血清抗氧化剂并未增加。与同样暴露于高氧环境的非黄疸幼崽相比，暴露于高氧环境的黄疸幼崽的相对肺重量较低，提示高氧诱导的肺水肿有所减轻。我们未检测到胆红素对实体组织脂质过氧化参数有显著影响。我们得出结论，在暴露于高氧环境的新生冈恩大鼠出生后的头几天，血清胆红素可防止血清氧化损伤。我们推测，胆红素在人类新生儿循环中是一种功能上重要的过渡性抗氧化剂，并且它可能参与调节高氧所致的损伤。
