Attenuation by ambroxol of monochloramine-enhanced gastric carcinogenesis: a possible prevention against Helicobacter pylori-associated gastric carcinogenesis.
The effects of combined administration of a reactive oxidant, monochloramine, and a mucoregulatory agent, ambroxol, on the development of gastric cancers induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) were investigated in inbred Wistar rats. After receiving oral MNNG and regular chow pellets for 25 weeks, rats received regular chow pellets or chow pellets containing 20% ammonium acetate, and normal tap water or water containing 30 mM sodium hypochlorite, with or without subcutaneous injection of ambroxol at high or low doses, until the end of the experiment at week 52. Treatment with both ammonium acetate and sodium hypochlorite, which produce monochloramine, significantly increased the incidence of gastric cancers at week 52, whereas concomitant administration of ambroxol with ammonium acetate and sodium hypochlorite significantly attenuated this enhanced gastric carcinogenesis. Results also revealed that ambroxol scavenged monochloramine. Because monochloramine is closely related to Helicobacter pylori-associated gastric carcinogenesis, these findings suggest that ambroxol may prevent H. pylori-associated gastric carcinogenesis.
Narahara
H
H
Department of Gastrointestinal Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, 3-3, Nakamichi 1-chome, Higashinari-ku, 537-8511, Osaka, Japan. narahara@dl.dion.ne.jp
Tatsuta
M
M
Iishi
H
H
Baba
M
M
Mikuni
T
T
Uedo
N
N
Sakai
N
N
Yano
H
H
D000551:Ambroxol / Q000494:pharmacology*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002273:Carcinogens / Q000633:toxicity; D002700:Chloramines / Q000037:antagonists & inhibitors / Q000633:toxicity*; D004347:Drug Interactions; D016166:Free Radical Scavengers / Q000494:pharmacology; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology; D016481:Helicobacter Infections / Q000150:complications / Q000378:metabolism; D016480:Helicobacter pylori / Q000378:metabolism; D008297:Male; D008769:Methylnitronitrosoguanidine / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D013274:Stomach Neoplasms / Q000139:chemically induced* / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control*
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D002700:Chloramines; D016166:Free Radical Scavengers; D008769:Methylnitronitrosoguanidine; D000551:Ambroxol; C030816:chloramine