Lipid Oxidation Products in the Pathogenesis of Inflammation-related Gut Diseases

Abstract

Background: A defective mucosal barrier function is the principal cause of the uncontrolled onset and progression of a number of human inflammatory gut diseases, most of which are characterized by chronic intermittent immune and inflammatory responses leading to structural intestinal damage, which can represent a potential risk for colorectal cancer development. During the active disease phase the production of pro-inflammatory cytokines and chemokines, and the induction of oxidative reactions by activated leukocytes and epithelial cells represent the main event in the intestinal inflammation. Objective: Oxidative stress plays a key role in the development of intestinal damage. Indeed reactive oxygen species and their oxidized by-products regulate redox-sensitive signaling pathways and transcription factors, which sustain inflammation within the intestinal layer. Methods: Polyunsaturated fatty acids and cholesterol are the principal targets of oxidative modifications. These lipids, which are cell membrane constituents or are present in food, readily undergo non-enzymatic oxidation to form chemically-reactive species that can induce a wide range of biological effects including inflammation, programmed cell death, and proliferation. Results and Conclusions: In this review we summarize the current knowledge on the role of lipid oxidation products in regulating redox pathways involved in the pathogenesis of inflammation- related gut diseases. In particular, lipid peroxidation end products, such as isoprostanes and aldehydes, and cholesterol oxidation-derived oxysterols are taken into consideration. Results and Conclusions: The control of oxidative damage and consequently tissue local over-production of lipid oxidation products by using specific antioxidant and anti-inflammatory molecules in the diet may have clinical and therapeutic benefits.