Statins lower plasma and lymphocyte ubiquinol/ubiquinone without affecting other antioxidants and PUFA

Issue title: The Third Conference of the International CoQ10 Association

Article type: Research Article

Authors: Passi, Siro | Stancato, Andrea | Aleo, Enrico | Dmitrieva, Anna | Littarru, Gian Paolo

Affiliations: Centro Invecchiamento Cellulare, I.D.I. (IRCCS), Roma, Italy | Facoltà di Medicina, Istituto di Biochimica, Ancona, Italy

Note: [] Address for correspondence: Tel.: +39 06 91092317; Fax: +39 06 91627082; E-mail: invcell@idi.it

Abstract: It has been shown that treating hypercholesterolemic patients (HPC) with statins leads to a decrease, at least in plasma, not only in cholesterol, but also in important non-sterol compounds such as ubiquinone (CoQ_{10}), and possibly dolichols, that derive from the same biosynthetic pathway. Plasma CoQ_{10} decrease might result in impaired antioxidant protection, therefore leading to oxidative stress. In the present paper we investigated the levels in plasma, lymphocytes and erythrocytes, of ubiquinol and ubiquinone, other enzymatic and non-enzymatic lipophilic and hydrophilic antioxidants, polyunsaturated fatty acids of phosfolipids and cholesterol ester fractions, as well as unsaturated lipid and protein oxidation in 42 hypercholesterolemic patients treated for 3 months. The patients were treated with different doses of 3 different statins, i.e. atorvastatin 10 mg (n = 10) and 20 mg (n = 7), simvastatin, 10 mg (n = 5) and 20 mg (n = 10), and pravastatin, 20 mg (n = 5) and 40 mg (n = 5). Simvastatin, atorvastatin and pravastatin produced a dose dependent plasma depletion of total cholesterol (t-CH), LDL-C, CoQ_{10}H_{2}, and CoQ_{10}, without affecting the CoQ_{10}H_{2}/CoQ_{10}ratio. The other lipophilic antioxidants (d-RRR-α-tocopherol-vit E-, γ-tocopherol, vit A, lycopene, and β-carotene), hydrophilic antioxidants (vit C and uric acid), as well as, TBA-RS and protein carbonyls were also unaffected. Similarly the erythrocyte concentrations of GSH and PUFA, and the activities of enzymatic antioxidants (Cu,Zn-SOD, GPx, and CAT) were not significantly different from those of the patients before therapy. In lymphocytes the reduction concerned CoQ_{10}H_{2}, CoQ_{10}, and vit E; other parameters were not investigated. The observed decline of the levels of CoQ_{10}H_{2} and CoQ_{10} in plasma and of CoQ_{10}H_{2}, CoQ_{10} and vit E in lymphocytes following a 3 month statin therapy might lead to a reduced antioxidant capacity of LDL and lymphocytes, and probably of tissues such as liver, that have an elevated HMG-CoA reductase enzymatic activity. However, this reduction did not appear to induce a significant oxidative stress in blood, since the levels of the other antioxidants, the pattern of PUFA as well as the oxidative damage to PUFA and proteins resulted unchanged. The concomitant administration of ubiquinone with statins, leading to its increase in plasma, lymphocytes and liver may cooperate in counteracting the adverse effects of statins, as already pointed out by various authors on the basis of human and animal studies.

Journal: BioFactors, vol. 18, no. 1-4, pp. 113-124, 2003