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

目的研究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代谢的影响，以及补充谷胱甘肽(GSH)的影响。其次，为了更好地了解外源性EGF对因摄入过氧化脂肪而引起的氧化应激所致的肠道增殖的影响。动物随机饲喂标准大鼠饲料或过氧化脂质饲料，连续4周。用硫代巴比妥酸比色法测定过氧化氢含量。雄性SD大鼠在处死前禁食24小时。DNA断裂法测定肠粘膜细胞凋亡率。以粘膜ODC活性作为细胞增殖活性的指标。在饮水中添加1%GSH的过氧化氢。与对照组相比，过氧化应激组大鼠肠黏膜脂质过氧化水平升高。同时检测细胞程序性死亡率和ODC活性。结果与讨论慢性过氧化脂质摄入可导致体内谷胱甘肽氧化还原失衡，干扰肠道细胞死亡和增殖的调节。补充GSH可使组织GSH-GSSG氧化还原平衡正常化，从而逆转脂质过氧化的这些干扰作用。EGF可逆转慢性过氧化脂质摄入对肠道ODC活性的抑制作用。相反，EGF显著提高过氧化应激大鼠结肠的增殖活性。这种夸大的增殖可能有助于更好地了解结肠对氧化剂诱导的恶变的易感性。

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.