Antibacterial and anti-atrophic effects of a highly soluble, acid stable UDCA formula in Helicobacter pylori-induced gastritis.
Helicobacter pylori is one of the main causes of atrophic gastritis and gastric carcinogenesis. Gastritis can also occur in the absence of H. pylori as a result of bile reflux suggesting the eradication of H. pylori by bile acids. However, the bile salts are unable to eradicate H. pylori due to their low solubility and instability at acidic pH. This study examined the effect of a highly soluble and acid stable ursodeoxycholic acid (UDCA) formula on H. pylori-induced atrophic gastritis. The H. pylori infection decreased the body weight, mitochondrial membrane potential and ATP level in vivo. Surprisingly, H. pylori-induced expression of malate dehydrogenase (MDH), a key enzyme in the tricarboxylic acid cycle, at both the protein and mRNA levels. However, the UDCA formula repressed MDH expression and increased the membrane potential thereby increasing the ATP level and body weight in vivo. Moreover, UDCA scavenged the reactive oxygen species (ROS), increased the membrane potential, and inhibited apoptosis in AGS cells exposed to H(2)O(2) in vitro through the mitochondria-mediated pathway. Taken together, UDCA decreases the MDH and ROS levels, which can prevent apoptosis in H. pylori-induced gastritis.
Thao
Tran Dang Hien
TD
College of Pharmacy, Sungkyunkwan University, Su-won 440-746, South Korea.
Ryu
Ho-Cheol
HC
Yoo
Seo-Hong
SH
Rhee
Dong-Kwon
DK
D000230:Adenocarcinoma / Q000188:drug therapy; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D004304:Dosage Forms; D016166:Free Radical Scavengers; D005757:Gastritis, Atrophic / Q000188:drug therapy* / Q000382:microbiology; D005786:Gene Expression Regulation / Q000187:drug effects; D016481:Helicobacter Infections / Q000188:drug therapy* / Q000382:microbiology; D016480:Helicobacter pylori / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D008291:Malate Dehydrogenase / Q000378:metabolism; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species; D013274:Stomach Neoplasms / Q000188:drug therapy; D013997:Time Factors; D014580:Ursodeoxycholic Acid / Q000494:pharmacology / Q000627:therapeutic use*
D000900:Anti-Bacterial Agents; D004304:Dosage Forms; D016166:Free Radical Scavengers; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D014580:Ursodeoxycholic Acid; D006861:Hydrogen Peroxide; D008291:Malate Dehydrogenase