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

点击翻译按钮获取中文摘要

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.