Amelioration of oxidative stress with ensuing inflammation contributes to chemoprevention of H. pylori-associated gastric carcinogenesis.
The gastric inflammatory response provoked by Helicobacter pylori (H. pylori) consists of infiltrations by neutrophils, lymphocytes, and macrophages, resulting in varying degrees of epithelial cell damage. H. pylori-associated inflammation not only activates various oxidant-producing enzymes such as NADPH oxidase and inducible nitric oxide synthase, but also lowers the antioxidant ascorbic acid in the stomach. Reactive oxygen metabolites and nitrogen metabolites generated by these enzymes react with each other to generate new or more potent reactive species. The specific types of cellular damage resulting from reactive oxygen metabolites include lipid peroxidation, protein oxidation, and oxidative DNA damage. All of these oxidative products can result in biochemical changes leading to cancer. A positive association has been demonstrated between H. pylori infection and gastric adenocarcinoma with increased oxidative stress. Therefore, appropriate treatment to reduce oxidative stress would be expected to prevent subsequent gastric carcinogenesis through lessening of H. pylori-associated inflammation. This review will provide evidence that antiinflammatory regimens can decrease the development of tumors and the amelioration of gastric inflammation might lead to chemoprevention strategies by the attenuation of oxidative stress.
Park
Soojin
S
Genomic Research Center for Gastroenterology, Ajou University School of Medicine, Suwon, Korea.
Kim
Won Seok
WS
Choi
Un Jung
UJ
Han
Sang Uk
SU
Kim
Yong Seok
YS
Kim
Young Bae
YB
Chung
Myung Hee
MH
Nam
Ki-Tak
KT
Kim
Dae Yong
DY
Cho
Sung Won
SW
Hahm
Ki-Baik
KB
D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics; D003849:Deoxyguanosine / Q000378:metabolism; D005756:Gastritis / Q000382:microbiology; D044404:Genomic Islands; D016480:Helicobacter pylori / Q000378:metabolism*; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D008954:Models, Biological; D019255:NADPH Oxidases / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D016877:Oxidants / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D011956:Receptors, Cell Surface / Q000378:metabolism; D013274:Stomach Neoplasms / Q000382:microbiology* / Q000473:pathology*; D013997:Time Factors; D051193:Toll-Like Receptors
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D008562:Membrane Glycoproteins; D016877:Oxidants; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors; C080866:cagA protein, Helicobacter pylori; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D019255:NADPH Oxidases; D003849:Deoxyguanosine