Friel James K, Diehl-Jones William L, Suh Miyoung, Tsopmo Apollinaire, Shirwadkar Vaibhav P
Department of Human Nutritional Sciences, University of Manitoba, Winnipeg, Manitoba, Canada R3T 2N2.
Free Radic Biol Med. 2007 May 15;42(10):1591-8. doi: 10.1016/j.freeradbiomed.2007.02.022. Epub 2007 Feb 28.
Stress due to reactive oxygen species (ROS) may lead to neonatal diseases, such as necrotizing enterocolitis and respiratory distress. Enteral supplements for premature infants (PREM) added to human milk (HM) to increase nutrient content may induce lipid oxidation due to free radical formation via Fenton chemistry. We hypothesized that ferrous iron and vitamin C-containing supplements added to HM in vitro cause oxidation of milk fats, affect intracellular redox balance, and induce DNA damage. Lipid peroxidation in HM was measured by FOX-2 and TBARS assays; fatty acid composition of supplemented HM was measured by gas chromatography. Two cell culture bioassays were used for assessing either intracellular oxidative stress or DNA damage: the former involved Caco-2BBe cells, a secondary differentiated cell line, and the latter utilized FHS-74 Int cells, a primary fetal small intestinal culture. Lipid oxidation products of HM increased after the addition of iron alone, iron and vitamin C, or iron and a vitamin C-containing supplement (Trivisol, TVS). A reduced content of mono and polyunsaturated fatty acids in HM was also observed. Iron, not iron+vitamin C, but iron+TVS induced significant intracellular oxidative stress in FHS-74 Int cells. In contrast, iron, either alone or in combination with TVS or vitamin C, increased DNA damage in Caco-2BBE cells. Iron supplementation may increase oxidative stress in PREM infants and should be given separately from vitamin C-containing supplements.
活性氧（ROS）产生的应激可能导致新生儿疾病，如坏死性小肠结肠炎和呼吸窘迫。添加到母乳（HM）中以增加营养成分的早产儿肠内补充剂（PREM）可能会因通过芬顿化学产生自由基而诱导脂质氧化。我们假设，在体外添加到HM中的含亚铁和维生素C的补充剂会导致乳脂肪氧化，影响细胞内氧化还原平衡，并诱导DNA损伤。通过FOX-2和TBARS测定法测量HM中的脂质过氧化；通过气相色谱法测量补充HM的脂肪酸组成。使用两种细胞培养生物测定法评估细胞内氧化应激或DNA损伤：前者涉及二次分化细胞系Caco-2BBe细胞，后者使用原代胎儿小肠培养物FHS-74 Int细胞。单独添加铁、铁和维生素C或铁和含维生素C的补充剂（Trivisol，TVS）后，HM的脂质氧化产物增加。还观察到HM中单不饱和脂肪酸和多不饱和脂肪酸含量降低。铁，而非铁加维生素C，但铁加TVS在FHS-74 Int细胞中诱导了显著的细胞内氧化应激。相比之下，单独的铁或与TVS或维生素C联合使用时，会增加Caco-2BBE细胞中的DNA损伤。补充铁可能会增加PREM婴儿的氧化应激，应与含维生素C的补充剂分开给予。
