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BMC Cancer  2011 

Pitavastatin suppresses diethylnitrosamine-induced liver preneoplasms in male C57BL/KsJ-db/db obese mice

DOI: 10.1186/1471-2407-11-281

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Abstract:

Male db/db mice were administered tap water containing 40 ppm DEN for 2 weeks and were subsequently fed a diet containing 1 ppm or 10 ppm pitavastatin for 14 weeks.At sacrifice, feeding with 10 ppm pitavastatin significantly inhibited the development of hepatic premalignant lesions, foci of cellular alteration, as compared to that in the untreated group by inducing apoptosis, but inhibiting cell proliferation. Pitavastatin improved liver steatosis and activated the AMPK-α protein in the liver. It also decreased free fatty acid and aminotransferases levels, while increasing adiponectin levels in the serum. The serum levels of tumor necrosis factor (TNF)-α and the expression of TNF-α and interleukin-6 mRNAs in the liver were decreased by pitavastatin treatment, suggesting attenuation of the chronic inflammation induced by excess fat deposition.Pitavastatin is effective in inhibiting the early phase of obesity-related liver tumorigenesis and, therefore, may be useful in the chemoprevention of liver cancer in obese individuals.Hepatocellular carcinoma (HCC) is a serious healthcare problem worldwide because of its increasing morbidity and high mortality. Chronic inflammation of the liver and subsequent cirrhosis, which are highly correlated with hepatitis B and hepatitis C viruses infection and alcoholic liver disease, are the strongest risk factors for HCC development. Recent evidence also indicates that obesity and related metabolic abnormalities, especially diabetes mellitus and insulin resistance, raise the risk of HCC [1-4]. In obese individuals, high levels of free fatty acid (FFA) flux into the liver from excess adipose tissue. This in turn promotes hepatic steatosis and inflammation through the production of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α and interleukin (IL)-6, and is closely associated with liver carcinogenesis [5-7]. Aberrant lipogenesis in the liver, which is closely linked to obesity and metabolic syndrome, is also a domina

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