It has been suggested that
hyperlipidemia is positively associated with colon
carcinogenesis.
Statins, 3-hydroxy-3-methyl-glutaryl-coenzyme A
reductase inhibitors, reduce serum
lipid levels. In this study, we clarified the effects of a novel chemically synthesized
statin,
pitavastatin, on
intestinal polyp formation in Min mice, and further examined serum
lipid and
adipocytokine levels, and proinflammatory and
adipocytokine gene levels in intestinal mucosa of Min mice. Treatment with
pitavastatin at doses of 20 and 40 ppm decreased the total number of
polyps dose-dependently to 85.2% and 65.8% (P < 0.05) of the untreated value, respectively. Serum levels of total
cholesterol and
triglyceride were slightly reduced and those of
IL-6,
leptin, and MCP-1 were decreased by 40-ppm
pitavastatin treatment.
mRNA expression levels of
cyclooxygenase-2,
IL-6, inducible
nitric oxide (iNOS), MCP-1, and
Pai-1 were significantly reduced in intestinal nonpolyp parts by
pitavastatin treatment. Among them, iNOS
mRNA levels were also reduced in the
intestinal polyps. Moreover, oxidative stress represented by
8-nitroguanosine in the small intestinal epithelial cells was reduced by
pitavastatin treatment. Related to these proinflammatory genes, PPARĪ³ activity was activated in the intestinal nonpolyp parts and in the liver of Min mice with
pitavastatin treatment. These results indicated that
pitavastatin has potential benefit for the suppression of
intestinal polyp development.