Pitavastatin suppresses diethylnitrosamine-induced liver preneoplasms in male C57BL/KsJ-db/db obese mice.
Pitavastatin suppresses diethylnitrosamine-induced liver preneoplasms in male C57BL/KsJ-db/db obese mice.
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DOI：
10.1186/1471-2407-11-281
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发表时间：
2011-06-28
期刊：
影响因子：
3.8
通讯作者：
Moriwaki H
中科院分区：
文献类型：
--
作者：
Shimizu M;Yasuda Y;Sakai H;Kubota M;Terakura D;Baba A;Ohno T;Kochi T;Tsurumi H;Tanaka T;Moriwaki H
肥胖和相关的代谢异常，包括炎症和肝脏中的脂肪堆积，在肝癌的发生中发挥了作用。脂肪细胞因子失衡，如血清脂联素水平降低，也与肥胖相关的肝脏肿瘤的发生有关。在本研究中，我们观察了治疗高脂血症的药物匹伐他汀对二乙基亚硝胺(DEN)诱导的C57BL/KSJ-db/db(db/db)肥胖小鼠肝脏癌前病变的影响。雄性db/db小鼠饮用含40ppm DEN的自来水2周，然后喂以含1ppm或10ppm倍他汀的饲料14周。在处死时，与未处理组相比，10ppm的匹伐他汀显著抑制了肝脏癌前病变的发展，这是通过诱导细胞凋亡，但抑制细胞增殖而实现的。他汀能改善肝脏脂肪变性，并激活肝脏中的AMPK-α蛋白。它还降低了游离脂肪酸和转氨酶的水平，同时提高了血清中的脂联素水平。匹伐他汀可降低血清肿瘤坏死因子-α水平及肝脏肿瘤坏死因子-α和白介素6mRNAs的表达，提示其对脂肪沉积过多所致的慢性炎症有一定的保护作用。匹伐他汀在抑制肥胖相关的肝脏肿瘤发生的早期阶段是有效的，因此，可能在肥胖个体的肝癌的化学预防中有用。
Obesity and related metabolic abnormalities, including inflammation and lipid accumulation in the liver, play a role in liver carcinogenesis. Adipocytokine imbalances, such as decreased serum adiponectin levels, are also involved in obesity-related liver tumorigenesis. In the present study, we examined the effects of pitavastatin - a drug used for the treatment of hyperlipidemia - on the development of diethylnitrosamine (DEN)-induced liver preneoplastic lesions in C57BL/KsJ-db/db (db/db) obese mice. 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.
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影响因子：
15.9
作者：
KITA, T;BROWN, MS;GOLDSTEIN, JL
通讯作者：
GOLDSTEIN, JL
影响因子：
1.9
作者：
Egawa, T;Toda, K;Onishi, S
通讯作者：
Onishi, S
影响因子：
8.3
作者：
Sata, M;Nishimatsu, H;Nagai, R
通讯作者：
Nagai, R
影响因子：
4.2
作者：
Muto, Yasutoshi;Sato, Shunichi;Ohashi, Yasuo
通讯作者：
Ohashi, Yasuo
影响因子：
9.8
作者：
Hyogo, Hideyuki;Tazuma, Susumu;Chayama, Kazuaki
通讯作者：
Chayama, Kazuaki