Roles of Lipid Peroxidation-Derived Electrophiles in Pathogenesis of Colonic Inflammation and Colon Cancer

Abstract

Redox stress is a common feature of gut disorders such as colonic inflammation (inflammatory bowel disease or IBD) and colorectal cancer (CRC). This leads to increased colonic formation of lipid-derived electrophiles (LDEs) such as 4-hydroxynonenal (4-HNE), malondialdehyde (MDA), trans, trans-2,4-decadienal (tt-DDE), and epoxyketooctadecenoic acid (EKODE). Recent research by us and others support that treatment with LDEs increases the severity of colitis and exacerbates the development of colon tumorigenesis in vitro and in vivo, supporting a critical role of these compounds in the pathogenesis of IBD and CRC. In this review, we will discuss the effects and mechanisms of LDEs on development of IBD and CRC and lifestyle factors, which could potentially affect tissue levels of LDEs to regulate IBD and CRC development.

Oxidized Linoleic Acid Interacts With Gut Microbiota to Promote Colitis and Colorectal Cancer

“…Indeed, our recent analysis of the Cancer Genome Atlas (TCGA) database showed that compared with healthy controls, the expression of a series of protective and antioxidant genes are signi cantly reduced in human colorectal tumor samples 24 , suggesting a dysfunctional antioxidant defense system in colorectal cancer patients. A similar dysfunctional antioxidant system is also observed in IBD 23 . Based on our ndings, the individuals with or prone to IBD and/or colorectal cancer could be susceptible to the adverse effects of oxidized LA, and these high-risk individuals may need to reduce the consumption of food products containing high levels of oxidized LA, though further studies are needed before dietary recommendations could be established.…”

“…Previous studies have also shown that oxidized LA had little effect to initiate diseases: Nolen et al treated healthy rats with frying oils, which contain high levels of oxidized LA, and found no pathological disorders in the treated animals after a 2-year treatment 22 . This could be, at least in part, because the mammalian system has an array of protective and antioxidant mechanisms to counteract the potential detrimental effects of lipid oxidationderived molecules; in contrast, the individuals with or prone to IBD and/or colorectal cancer have a compromised antioxidant defense system and therefore could be susceptible to the adverse effects of oxidized LA 23 . Indeed, our recent analysis of the Cancer Genome Atlas (TCGA) database showed that compared with healthy controls, the expression of a series of protective and antioxidant genes are signi cantly reduced in human colorectal tumor samples 24 , suggesting a dysfunctional antioxidant defense system in colorectal cancer patients.…”

The effect of acute oral galactose administration on the redox system of the rat small intestine

“…The concept that disbalance between electrophilic and nucleophilic tone encourages initiation and propagation, and delays the termination step of lipid peroxidation is central to most theories of oxidative stress-induced pathophysiological states (at least those predominantly defined by the excess of electrophiles [66,67]) and accumulation of lipid peroxidation end products is evident in many pathological states including those affecting the gastrointestinal tract (e.g. reflux esophagitis, gastritis, gastric ulcers and H.pylori infection, and inflammatory bowel disease [31,[68][69][70]).…”

Chemistry and Biochemistry Aspects of the 4-Hydroxy-2,3-trans-nonenal

“…The role of HNE in the development of neoplastic cells was mentioned above. Besides, the evidence suggesting a role for HNE in the pathogenesis of many types of cancer also has been reviewed in many papers [ 57 , 58 , 59 , 60 , 61 ]. It is known that in pathological conditions elevated levels of HNE-modified molecules are found in the blood and other tissues.…”