Effect of light exposure on metalloporphyrin-treated newborn mice.
Effect of light exposure on metalloporphyrin-treated newborn mice.
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光暴露对金属卟啉治疗的新生小鼠的影响。
DOI：
10.1038/pr.2012.62
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发表时间：
2012
影响因子：
3.6
通讯作者：
Stevenson,DavidK
中科院分区：
文献类型：
--
作者：
Schulz,Stephanie;Wong,RonaldJ;Kalish,FloraS;Zhao,Hui;Jang,KyuYun;Vreman,HendrikJ;Stevenson,DavidK
背景：新生儿高胆红素血症是由胆红素生成增加和胆红素清除减少引起的。尽管光疗安全有效地降低了胆红素水平，但最近的证据表明，它有不良影响。因此，替代治疗是有必要的。金属卟啉是血红素加氧酶(HO)的竞争性抑制剂，是胆红素生产中的限速酶，有效地减少胆红素的形成；然而，许多金属卟啉是光反应的。方法和结果：给3d龄小鼠灌胃染毒(3.75~30.0µmol/kg)，暴露于冷白色(F20T12CW)和蓝色(TL20W/52)荧光灯(+L)中3h，可引起剂量依赖性死亡(半数致死剂量分别为21.5和19.5µmol/kg)。与锌BG相比，复方新诺明+L组和复方新诺明组小鼠的存活率无显著差异。在30µmol/kg锌BG+L治疗后，我们发现体重显著减轻，肝脏抗氧化能力降低，天冬氨酸氨基转移酶水平升高。光照后6d，锌BG+L处理组大鼠皮肤大体及组织学改变。经30微克分子锌BG/kg处理后，再经蓝色发光二极管照射，未观察到致死作用。结论：低剂量(3.75µm o l/kg)的锌BG具有最大的HO抑制活性，且无光敏作用，可用于新生儿高胆红素血症的治疗。
Background:Neonatal hyperbilirubinemia arises from increased bilirubin production and decreased bilirubin elimination. Although phototherapy safely and effectively reduces bilirubin levels, recent evidence shows that it has adverse effects. Therefore, alternative treatments are warranted. Metalloporphyrins, competitive inhibitors of heme oxygenase (HO), the rate-limiting enzyme in bilirubin production, effectively reduce bilirubin formation; however, many are photoreactive. Here, we investigated possible photosensitizing effects of chromium mesoporphyrin (CrMP) and zinc deuteroporphyrin bis-glycol (ZnBG).Methods and Results:Administration of CrMP or ZnBG to 3-d-old mouse pups (3.75–30.0 µmol/kg intraperitoneally) and exposure to cool white (F20T12CW) and blue (TL20W/52) fluorescent lights (+ L) for 3 h, resulted in a dose-dependent mortality (50% lethal dose (LD50)= 21.5 and 19.5 µmol/kg, respectively). In contrast to ZnBG, there was no significant difference in survival between the CrMP+ L and CrMP groups. Following 30 µmol/kg ZnBG+ L, we found significant weight loss, decreased liver antioxidant capacities, and increased aspartate aminotransaminase levels. At 6-d post-light exposure, ZnBG+ L-treated pups showed gross and histologic skin changes at doses> 7.5 µmol/kg. No lethality was observed following treatment with 30 µmol ZnBG/kg plus exposure to blue light-emitting diodes. Phototoxicity of ZnBG was dependent on light source, emission spectrum, and irradiance.Conclusion:Low doses of ZnBG (< 3.75 µmol/kg) retained maximal HO inhibitory potency without photosensitizing effects, and therefore are potentially useful in treating neonatal hyperbilirubinemia.