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

Abstract

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 generally regarded as a biomarker of mutagenesis consequent 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-κB signaling pathway, and ameliorate the expression of proinflammatory mediators such as interleukin (IL)-1, IL-6, cyclo-oxygenase-2, and inducible nitric oxide synthase in addition to expression of nicotinamide adenine dinucleotide phosphate oxidase (NOX)-1, NOX organizer-1 and NOX activator-1 in various conditions of inflammation-based gastrointestinal (GI) diseases including gastritis, inflammatory bowel disease, pancreatitis, and even colitis-associated carcinogenesis. 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 prevention 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.

8-hydroxy-2’-deoxyguanosine in colorectal adenocarcinoma – is it a result of oxidative stress?

“…This is the reason why 8-OHdG has been used in many studies as a biomarker for the measurement of endogenous oxidative DNA damage, and as a risk factor for many diseases such as cancer or degenerative diseases [46]. The idea of using oxidative DNA damage, like 8-OHdG, as a biomarker of oxidative stress, chronic inflammation, and susceptibility to cancer, gives a new perspective.…”

Molecular Basis of Pterygium Development

“…43,47 In addition to the antioxidant function, the generation of this molecule can be one of the defense mechanisms of cells against oxidative-stress-induced inflammation. 48 The presence of 8-OHdG in cellular DNA can be diminished by the enzyme hOGG1 (human 8-oxoguanine glycosylase I), which has been shown to be overexpressed in pterygium tissue. 47 Since the increase of 8-OHdG was not correlated to a decrease in hOGG1 expression, further analyses were conducted to determine whether this enzyme had undergone modifications which could explain the loss of its effectiveness.…”

Biological role of 8-oxo-2'-deoxyguanosine

“…Точный механизм этого воз-действия пока не известен, но выявлено снижение активности НАДФ·H-оксидазы, ингибирование RAC-связанных функций, ограничение фосфорилиро-вания киназы STAT-1, подавление транскрипции циклооксигеназы-2, интерлейкинов 1 и 6, фактора адгезии макрофагов [22][23][24][25]. Противовоспалитель-ное действие 8-oxo-dG показано на моделях ате-росклероза и язвенной болезни желудка [26].…”