Chronic lipid hydroperoxide stress suppresses mucosal proliferation in rat intestine: potentiation of ornithine decarboxylase activity by epidermal growth factor

Abstract

We recently demonstrated that chronic exposure of rat intestine to sublethal levels of peroxidized lipids suppresses ornithine decarboxylase (ODC) activity, consistent with attenuated intestinal proliferation. The current study was designed to better understand the influence of exogenous epidermal growth factor (EGF) on intestinal proliferation in normal intestine and intestine that was challenged by oxidative stress induced by dietary consumption of peroxidized lipids. Male Sprague-Dawley rats (250-300 g) were fed standard chow (control) or peroxidized lipid chow for 4 weeks. EGF was injected intraperitoneally at a dose of 40 microg/kg. Intestinal proliferation was evaluated by ODC activity in fed or fasted states and at specified times during the circadian phase. Chronic peroxide consumption significantly attenuated ODC activities in association with increased tissue peroxide content. The suppressed ODC activities were restored to control values by EGF in the small intestine; in the colon, EGF increased ODC activity threefold over control rats given EGF. This elevated colonic ODC activity was correlated with decreased tissue GSSG and an increased GSH/GSSG ratio. These results show that EGF administration reverses the suppression of intestinal ODC activities induced by chronic peroxidized lipid intake. In contrast, EGF significantly elevates proliferative activity in the peroxide-stressed colon. This exaggerated proliferation may contribute to a better understanding of colonic susceptibility to oxidant-induced malignant transformation.