Lipid oxidation products in the pathogenesis of inflammation-related gut diseases

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 intestinal inflammation. 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. 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. 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. We also discuss the hypothesis that controlling 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.