Reduction of cholesterol and markers of oxidation in serum of hypercholestrolemic patients treated with lycosome formulation of simvastatin
Keywords:Simvastatin, Lycopene, Hypercholesterolemia, Oxidative stress
Background: Use of microencapsulated HMG-CoA reductase inhibitors (statins) might be extremely helpful in the prevention of their side effects.
Methods: 24 volunteers with hypercholesterolemia were given once daily 20 mg of lycosome-formulated Simvastatin fused with 7 mg lycopene (Lyco-Simvastatin) or the same amount of unmodified Simvastatin with no lycopene. Control patients received 7 mg of lycopene alone. Plasma lipids and oxidative markers were measured after 4 weeks of treatment.
Results: Both formulations of Simvastatin, but not lycopene, caused a reduction in serum total cholesterol and LDL at the intermediate (end of 2nd week) and final (end of 4th week) points of interventional period. Notably, reduction of total cholesterol and LDL in the 4th week of the trial was more profound in patients treated with Lyco-Simvastatin versus unmodified Simvastatin (P<0.05). Patients treated with Lyco-Simvastatin showed a reduction in serum Apo B level, which was not observed in other groups. Lycopene treatment caused a modest but statistically significant decrease in serum triglyceride. However, the triglyceride-lowering effect of Simvastatin was more profound in the case of Lyco-Simvastatin treatment. Lycopene as well as unmodified Simvastatin gave a marginal reduction of Inflammatory Oxidative Damage. Remarkably, the combined formulation of Simvastatin and lycopene gave a significant reduction in the values for oxidative damage (reduction of median by 112.5 µM, P<0.05). Similar synergistic effect was observed when levels of oxidized LDL were analyzed.
Conclusions: Lycosome-formulated microencapsulated Simvastatin has a better cholesterol-lowering and antioxidant capacity presumably due to enhanced bioavailability of the drug and synergism with lycopene.
Alvarado CM, Marín SA, Lima RJ. Statins and autoimmunity. Med Clin (Barc). 2015;S0025- 7753(14)00878-1.
Desai CS, Martin SS, Blumenthal RS. Non-cardiovascular effects associated with statins. BMJ. 2014;17:349.
Magni P, Macchi C, Morlotti B, Sirtori CR, Ruscica M. Risk identification and possible countermeasures for muscle adverse effects during statin therapy. Eur J Intern Med. 2015. pii: S0953-6205(15)00003-5.
Pasnoor M, Barohn RJ, Dimachkie MM. Toxic myopathies. Neurol Clin. 2014;32(3):647-70.
Rallidis LS1, Fountoulaki K, Anastasiou-Nana M. Managing the underestimated risk of statin-associated myopathy Int J Cardiol. 2012;6;159(3):169-76.
Yeganeh B, Wiechec E, Ande SR, Sharma P, Moghadam AR, Post M, et al. Targeting the mevalonate cascade as a new therapeutic approach in heart disease, cancer and pulmonary disease. Pharmacol Ther. 2014;143(1):87-110.
McKenney JM. Pharmacologic characteristics of statins. Clin Cardiol. 2003;26(4):III32-8.
Cui CJ, Li S, Li JJ. PCSK9 and its modulation. Clin Chim Acta. 2015;440C:79-86.
Petyaev IM, Improvement of hepatic bioavailability as a new step for statin future. Arch Med Sci. 2015.
Gazzerro P, Proto MC, Gangemi G, Malfitano AM, Ciaglia E, Pisanti S, et al. Pharmacological actions of statins: a critical appraisal in the management of cancer. Pharmacol Rev. 2012;64(1):102-46.
Stapleton PA, Goodwill AG, James ME, Brock RW, Frisbee JC. Hypercholesterolemia and microvascular dysfunction: interventional strategies.J Inflamm (Lond). 2010;7:54.
Gómez H, Mesquida J, Simon P. Characterization of tissue oxygen saturation and the vascular occlusion test: influence of measurement sites, probe sizes and deflation thresholds. Critical Care. 2009;13,(3):1-7.
Yagi K. Lipid peroxides and human diseases. Chemistry and Physics of Lipids. 1987;45,2-4:337-51.
Petyaev I, Mitchinson MMJ, Hunt JV, Coussons PJ. Superoxide dismutase activity of antibodies purified from the human arteries andatherosclerotic lesions. Biochemical Society Transactions. 1998;26(1):S43.
Petyaev IM, Coussons PJ. Superoxide dismutase activity of antibodies purified from human atherosclerotic lesions, in Superoxide Dismutase: Recent Advances and Clinical Applications. 1999:51-4.
Balakumar P, Mahadevan N. Interplay between statins and PPARs in improving cardiovascular outcomes: a double-edged sword? Br J Pharmacol. 2012;165(2):373-9.
Olson EA, Hainsworth DP, Davis G, Hagan JC. Eye on statins: A comprehensive review. Mo Med. 2013;110(4):344-8.
Romana B, Batger M, Prestidge CA, Colombo G, Sonvico F. Expanding the therapeutic potential of statins by means of Nanotechnology enabled drug delivery systems. Curr Top Med Chem. 2014;14(9):1182-93.
Poirier S, Mayer G. The biology of PCSK9 from the endoplasmic reticulum to lysosomes: new and emerging therapeutics to control low-density lipoprotein cholesterol. Drug Des Devel Ther. 2013;7:1135-48.
Webb J, Gonna H, Ray KK. Lipid management: maximizing reduction of cardiac risk. Clin Med. 2013;13(6):618-20.
Carotenoid particles and uses thereof. GB Patent Application No. 1101669.8, PCT/GB2012/000075, 25.01.2012.
Bravo E, Napolitano M. Mechanisms involved in chylomicron remnant lipid uptake by macrophages. Biochem Soc Trans. 2007;35(3):459-63.
Nasri H, Baradaran A, Shirzad H, Rafieian-Kopaei M. New concepts in nutraceuticals as alternative for pharmaceuticals. Int J Prev Med. 2014;5(12):1487-99
Li Y, Fu J, Yuan X, Hu C. Simvastatin inhibits the proliferation of A549 lung cancer cells through oxidative stress and up-regulation of SOD2. Pharmazie. 2014;69(8):610-4.
Vance TM, Su J, Fontham ET, Koo SI, Chun OK. Dietary antioxidants and prostate cancer: a review. Nutr Cancer. 2013;65(6):793-801.