Pitavastatin fails to lower serum lipid levels or inhibit gastric carcinogenesis in helicobacter pylori-infected rodent models.
Statins are commonly used lipid-lowering drugs that reduce the risk of cardiovascular morbidity and mortality. Although recent studies have pointed to chemopreventive effects of statins against various cancers, their efficacy for gastric cancer is unclear. Here, we examined the effects of pitavastatin, a lipophilic statin, on Helicobacter pylori (H. pylori)-associated stomach carcinogenesis and gastritis using Mongolian gerbil and mouse models. The animals were allocated to H. pylori + N-methyl-N-nitrosourea administration (gerbils, 52 weeks) or H. pylori infection alone groups (gerbils and mice, 12 weeks). After H. pylori infection, they were fed basal diets containing 0 to 10 ppm of pitavastatin. The incidences of H. pylori-associated gastric adenocarcinomas and degrees of chronic gastritis were not decreased by pitavastatin compared with those of control values. Expression of interleukin-1beta and tumor necrosis factor-alpha mRNAs in the pyloric mucosa was markedly up-regulated in pitavastatin-treated animals. Furthermore, in the H. pylori-infected groups, serum total cholesterol, triglyceride, and low-density lipoprotein levels were significantly increased by pitavastatin treatment, contrary to expectation. In the short-term study, H. pylori-infected gerbils and mice also showed significant up-regulation of serum triglyceride levels by pitavastatin, whereas total cholesterol was markedly reduced and low-density lipoprotein exhibited a tendency for decrease in noninfected animals. These findings indicate pitavastatin to be ineffective for suppressing gastritis and chemoprevention of gastric carcinogenesis in H. pylori-infected gerbils. Our serologic results also suggest that the H. pylori infection and consequent severe chronic gastritis interfere with the cholesterol-lowering effects of pitavastatin.
Toyoda
Takeshi
T
Division of Oncological Pathology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan.
Tsukamoto
Tetsuya
T
Takasu
Shinji
S
Hirano
Naoki
N
Ban
Hisayo
H
Shi
Liang
L
Kumagai
Toshiko
T
Tanaka
Takuji
T
Tatematsu
Masae
M
D000818:Animals; D002277:Carcinoma / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D005849:Gerbillinae; D016481:Helicobacter Infections / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D016480:Helicobacter pylori; D008055:Lipids / Q000097:blood*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D011804:Quinolines / Q000494:pharmacology / Q000627:therapeutic use*; D012377:Rodentia; D013274:Stomach Neoplasms / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D017211:Treatment Failure
D004791:Enzyme Inhibitors; D008055:Lipids; D011804:Quinolines; C108475:pitavastatin