Chessex Philippe, Lavoie Jean-Claude, Rouleau Thérèse, Brochu Pierre, St-Louis Patrick, Lévy Emile, Alvarez Fernando
Perinatal Service and Research Center, Hôpital Ste-Justine, Montreal, Quebec, Canada.
Pediatr Res. 2002 Dec;52(6):958-63. doi: 10.1203/00006450-200212000-00023.
Photooxidation of multivitamin solutions results in the generation of peroxides. Because peroxides are associated with hepatic steatosis and fibrosis as well as cholestasis, we questioned whether multivitamins are implicated in hepatic complications of parenteral nutrition. Guinea pig pups were assigned to groups receiving intravenously either total parenteral nutrition, photo-protected or not, or a control solution (5% dextrose + 0.45% NaCl) supplemented with either a) multivitamins; b) photo-protected multivitamins; c) multivitamins without riboflavin; or d) peroxides (H(2)O(2), tert-butylhydroperoxide). After 4 d, liver was sampled for histology and isoprostane-F(2alpha) levels, a marker of radical attack. Multivitamins as well as total parenteral nutrition were associated with steatosis (scored 0-4), the severity of which was reduced (p < 0.05) by photo protection. Although H(2)O(2) is the major peroxide contaminating multivitamins, it did not induce steatosis scores different than the controls. Compared with controls, hepatic isoprostane-F(2alpha) content increased in animals infused with H(2)O(2) (p < 0.05), but not in those infused with Multi-12 pediatric multivitamins or total parenteral nutrition. Results suggest that peroxides and/or free radicals are not mediators of the induction of steatosis observed with infusion of photo-exposed multivitamins, as there was no correspondence between histologic findings and hepatic levels of isoprostanes. It is suspected that a component of the multivitamin solution becomes hepato-toxic after photo-exposure, as indicated by the protective effect observed when withdrawing riboflavin. Photo-oxidation of multivitamins might be the common link between reports involving amino acids, lipids, and light exposure in the ethiology of hepatic complications of parenteral nutrition.
多种维生素溶液的光氧化会导致过氧化物的生成。由于过氧化物与肝脂肪变性、肝纤维化以及胆汁淤积有关，我们质疑多种维生素是否与肠外营养的肝脏并发症有关。将豚鼠幼崽分为几组，分别静脉输注全肠外营养（有无光保护）或对照溶液（5%葡萄糖+0.45%氯化钠），对照溶液中添加以下物质之一：a）多种维生素；b）光保护的多种维生素；c）不含核黄素的多种维生素；或d）过氧化物（过氧化氢、叔丁基过氧化氢）。4天后，采集肝脏样本进行组织学检查和异前列腺素F2α水平检测（自由基攻击的标志物）。多种维生素以及全肠外营养均与脂肪变性有关（评分0-4），光保护可降低其严重程度（p<0.05）。虽然过氧化氢是污染多种维生素的主要过氧化物，但它并未诱导出与对照组不同的脂肪变性评分。与对照组相比，输注过氧化氢的动物肝脏异前列腺素F2α含量增加（p<0.05），但输注多种维生素12儿科多种维生素或全肠外营养的动物则未增加。结果表明，过氧化物和/或自由基不是输注光暴露多种维生素后观察到的脂肪变性诱导的介质，因为组织学结果与肝脏异前列腺素水平之间没有相关性。怀疑多种维生素溶液的一种成分在光暴露后变得具有肝毒性，去除核黄素时观察到的保护作用表明了这一点。多种维生素的光氧化可能是肠外营养肝脏并发症病因学中涉及氨基酸、脂质和光照暴露的报道之间的共同联系。
