Chronic inflammation and oxidative stress

Abstract

Helicobacter pylori is the leading risk factor associated with gastric carcinogenesis. H. pylori leads to chronic inflammation because of the failure of the host to eradicate the infection. Chronic inflammation leads to oxidative stress, deriving from immune cells and from within gastric epithelial cells. This is a main contributor to DNA damage, apoptosis and neoplastic transformation. Both pathogen and host factors directly contribute to oxidative stress, including H. pylori virulence factors, and pathways involving DNA damage and repair, polyamine synthesis and metabolism, and oxidative stress response. Our laboratory has recently uncovered a mechanism by which polyamine oxidation by spermine oxidase causes H₂O₂ release, DNA damage and apoptosis. Our studies indicate novel targets for therapeutic intervention and risk assessment in H. pylori-induced gastric cancer. More studies addressing the many potential contributors to oxidative stress, chronic inflammation, and gastric carcinogenesis are essential for development of therapeutics and identification of gastric cancer biomarkers.

Keywords: :

• Helicobacter pylori
• oxidative stress
• DNA damage
• 8-oxoguanosine
• gastric carcinogenesis
• spermine oxidase
• stomach

Disclosure of Potential Conflicts of Interest

No potential conflict of interest was disclosed.

Acknowledgments

This work was supported by the National Institutes of Health grants R01DK053620, R01AT004821, P01CA028842, and P01CA116087 (to K.T.W.), the Vanderbilt University Digestive Disease Research Center supported by grant P30DK058404, UL1RR024975 (Vanderbilt CTSA, Pilot Project to K.T.W.), K01AT007324 (to R.C), and a Merit Review Grant 1I01BX001453 from the Office of Medical Research, Department of Veterans Affairs (to K.T.W.). D.M.H. was supported by NIH grant 5T32GM008554 and the Thomas F. Frist, Sr. endowment (to K.T.W.).