Lovastatin prevents carcinogenesis in a rat model for liver cancer. Effects of ubiquinone supplementation.
نویسندگان
چکیده
AIM This study tests the hypothesis that statins (HMGCoA reductase inhibitors) inhibit carcinogenesis and that this effect may be mediated by the statin-induced inhibition of ubiquinone synthesis. MATERIALS AND METHODS The effects of lovastatin, with and without addition of ubiquinone, were studied in a rat model for chemically induced hepatocarcinogenesis. Intermediates in the mevalonate pathway were measured. RESULTS Lovastatin treatment reduced the volume fraction of liver nodules by 50% and the cell proliferation within the liver nodules was reduced to one third. Ubiquinone (Q10) treatment reversed the statin-induced inhibition of cell proliferation. Lathosterol levels were reduced significantly in the statin-treated rats, indicating inhibition of the mevalonate pathway, but cholesterol levels were not affected. CONCLUSION Lovastatin inhibits carcinogenesis in a rat model for liver cancer, despite unaffected cholesterol levels. The statin-induced inhibition of cell proliferation may, at least in part, be explained by the inhibition of ubiquinone synthesis.
منابع مشابه
مقایسه اثرات درمانی لوواستاتین و ویتامین E بر حجم گلومرولهای کلیه در موشهای صحرایی دیابتی
Background and Aim: Diabetic nephropathy is the most common complication of diabetes. Oxidative stress has been suggested to play a key role in the pathogenesis of diabetic nephropathy. It has been shown that vitamin E and lovastatin delay the onset and progression of nephropathy. The purpose of this study was to determine the effects of supplementation of vitamin E and lovastatin on glomerular...
متن کاملEffects of Lovastatin and Pravastatin on ubiquinone and 4- hydroxynonenal tissue levels in the hypercholesterolemic hamster”
Further to our experiment which suggested that lovastatin treatment leads to a larger decrease of ubiquinone levels in rat tissues than pravastatin, we undertook to confirm this finding in the hypercholesterolemic hamster, a model that mimics the cholesterol regulatory mechanisms in humans. In view of the proposed antioxidant role of ubiquinone, we also tested the hypothesis that ubiquinone lev...
متن کاملUbiquinone supplementation during lovastatin treatment: effect on LDL oxidation ex vivo.
A randomized, double-masked, placebo-controlled cross-over trial was carried out to evaluate whether ubiquinone supplementation (180 mg daily) corrects impaired defence against initiation of oxidation of low density lipoprotein (LDL) related to effective (60 mg daily) lovastatin treatment. Nineteen men with coronary heart disease and hypercholesterolemia received lovastatin with or without ubiq...
متن کاملSelenium prevents tumor development in a rat model for chemical carcinogenesis.
Previous studies in animals and humans have shown that selenium compounds can prevent cancer development. In this work we studied the tumor preventive effect of selenium supplementation, administrated as selenite, in the initiation, promotion and progression phases in a synchronized rat model for chemically induced hepatocarcinogenesis, the resistant hepatocyte model. Selenite in supra-nutritio...
متن کاملPossible Involvement of Hepatic Phosphatidate Phosphohydrolase in the Mechanisms of Actions of Certain Antilipemic Drugs in Rats
The effects of therapeutic doses of dillsun, garsin, antum and statins on rat liver cytosolic phosphatidate phosphohydrolase (PAP) activity, a key enzyme in triacylglycerol synthesis, and on serum and liver lipids were examined. Lovastatin and simvastatin both stimulated the enzyme activity by 29% and 43%, respectively. The stimulatory effects were dose-dependent and accompanied by the decline ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Anticancer research
دوره 30 4 شماره
صفحات -
تاریخ انتشار 2010