The effect of chronic consumption of lipid peroxides on tumorigenesis in intestine : whether anti-oxidants suppresses tumorigenesis in intestine

目的探讨慢性摄入亚毒性水平的过氧化脂质对肠道氧化还原平衡和周转的影响以及补充谷胱甘肽（GSH）的作用。其次，我们设计的研究，以更好地了解外源性EGF对肠道增殖的影响，受到挑战的氧化应激引起的饮食消费的过氧化lipids.MethodsA定制的大鼠食物中含有4%的过氧化鲱鱼油的脂质过氧化物的来源。动物自由采食标准大鼠饲料或过氧化脂质饲料4周。用硫代巴比妥酸法测定过氧化氢含量。雄性SD大鼠在处死前禁食24小时。DNA片段化法检测肠黏膜细胞凋亡率。测量粘蛋白ODC活性作为增殖活性的标志物。我们在饮用水中补充了1%GSH。与对照组相比，过氧化氢喂养大鼠肠粘膜脂质过氧化物浓度升高。还检测了程序性细胞死亡率和ODC活性。EGF以40 μg/kg的剂量腹腔注射。结果与讨论结果表明，慢性脂质过氧化物消耗诱导GSH氧化还原失衡，干扰肠细胞死亡和增殖的调节在体内。这些破坏性的影响，脂质过氧化物逆转补充GSH按照正常化的组织GSH？GSSG氧化还原平衡EGF的管理逆转抑制肠ODC活动引起的慢性过氧化脂质摄入。相反，EGF显著提高了过氧化应激结肠的增殖活性。这种夸张的增殖可能有助于更好地了解结肠对氧化剂诱导的恶性转化的易感性。

AIMThis study examines the effect of chronic consumption of subtoxic levels of peroxidized lipids on intestinal redox balance and turnover and the effect of glutathione (GSH) supplementation. Secondly, we designed the study to better understand the influence of exogenous EGF on intestinal proliferation that was challenged by oxdative stress induced by dietary consumption of peroxidized lipids.MethodsA customized rat chow containing 4% peroxidized menhaden oil was the source of lipid peroxides. Animals were fed either standard rat chow ad libitum or the peroxidized lipid chow for 4 weeks. The peroxide contents was measured by thiobarbituric acid assay. Male SD rats were fasted for 24hrs prior to sacrifice. Rate of apoptosis in intestinal mucosa was measured by DNA fragmentation assay. Mucosal ODC activity was measured as the marker of proliferative activity. We supplemented peroxide fed animals with 1%GSH in the drinking water. Compared with control, lipid peroxide concentration in intestinal mucosa was elevated in peroxide fed rats. Rate of programmed cell death and ODC activity were also examined. EGF was injectedintraperitoneally at a dose of 40 μg/kg.Results & DiscussionThe results show that chronic lipid peroxide consumption induces GSH redox imbalance that interferes with regulation of enterocyte death and proliferation in vivo. These disruptive effects of lipid peroxides were reversed by GSH supplementation in accordance with the normalization of tissue GSH?GSSG redox balance. EGF administration reverses the suppression of intestinal ODC activities induced by chronic peroxidized lipid intake. IN contrast, EGF significantly elevates proliferative activity in the peroxidized-stressed colon. This exaggerated proliferation may contribute to better understanding of colonic susceptibility to oxidant-induced malignant transformation.