8-Hydroxydeoxyguanosine:Not mere biomarker for oxidative stress,but remedy for oxidative stress-implicated gastrointestinal diseases

Reactive oxygen species (ROS) attack guanine bases in DNA easily and form 8-hydroxydeoxyguanosine (8-OHdG),which can bind to thymidine rather than cytosine,based on which,the level of 8-OHdG is gen-erally regarded as a biomarker of mutagenesis conse-quent to oxidative stress.For example,higher levels of 8-OHdG are noted in Helicobacter pylori-associated chronic atrophic gastritis as well as gastric cancer.However,we have found that exogenous 8-OHdG can paradoxically reduce ROS production,attenuate thenuclear factor-κB signaling pathway,and ameliorate the expression of proinflammatory mediators such as interleukin (IL)-1,IL-6,cyclo-oxygenase-2,and induc-ible nitric oxide synthase in addition to expression of nicotinamide adenine dinucleotide phosphate oxidase (NOX)-1,NOX organizer-1 and NOX activator-1 in vari-ous conditions of inflammation-based gastrointestinal (GI) diseases including gastritis,inflammatory bowel disease,pancreatitis,and even colitis-associated carci-nogenesis.Our recent finding that exogenous 8-OHdG was very effective in either inflammation-based or oxidative-stress-associated diseases of stress-related mucosal damage has inspired the hope that synthetic 8-OHdG can be a potential candidate for the treatment of inflammation-based GI diseases,as well as the pre-vention of inflammation-associated GI cancer.In this editorial review,the novel fact that exogenous 8-OHdG can be a functional molecule regulating oxidative-stress-induced gastritis through either antagonizing Rac-guanosine triphosphate binding or blocking the signals responsible for gastric inflammatory cascade is introduced.