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

• Published in: World journal of gastroenterology : WJG 2012-01, Vol.18 (4), p.302-308
• Main Authors: Ock, Chan-Young, Kim, Eun-Hee, Choi, Duck Joo, Lee, Ho Jae, Hahm, Ki-Baik, Chung, Myung Hee
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents - metabolism; Anti-Inflammatory Agents - therapeutic use; Antineoplastic Agents - metabolism; Antineoplastic Agents - therapeutic use; Biomarkers - metabolism; Colitis - drug therapy; Deoxyguanosine - analogs & derivatives; Deoxyguanosine - metabolism; Deoxyguanosine - therapeutic use; Gastrointestinal Diseases - metabolism; Gastrointestinal Diseases - physiopathology; Humans; Inflammation - drug therapy; Oxidative Stress; Reactive Oxygen Species - metabolism; Stomach Neoplasms - drug therapy; Stomach Neoplasms - physiopathology; 信号转导通路; 氧化应激; 炎症介质; 烟酰胺腺嘌呤二核苷酸; 生物标志物; 羟基; 胃肠道疾病; 补救办法
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.v18.i4.302

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 the nuclear factor-KB signaling pathway, and ameliorate the expression of proinflammatory mediators such as interleukin （IL）-I, IL-6, cyclo-oxygenase-2, and induc- ible nitric oxide synthase in addition to expression of nicotinamide adenine dinucleotide phosphate oxidase （NOX）-I, 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.