Statins lower plasma and lymphocyte ubiquinol/ubiquinone without affecting other antioxidants and PUFA.
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 (CoQ10), and possibly dolichols, that derive from the same biosynthetic pathway. Plasma CoQ10 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, CoQ10H2, and CoQ10, without affecting the CoQ10H2/CoQ10 ratio. The other lipophilic antioxidants (d-RRR-alpha-tocopherol-vit E-, gamma-tocopherol, vit A, lycopene, and beta-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 CoQ10H2, CoQ10, and vit E; other parameters were not investigated. The observed decline of the levels of CoQ10H2 and CoQ10 in plasma and of CoQ10H2, CoQ10 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.
Passi
Siro
S
Centro Invecchiamento Cellulare, I.D.I. (IRCCS), Roma, Italy. invcell@idi.it
Stancato
Andrea
A
Aleo
Enrico
E
Dmitrieva
Anna
A
Littarru
Gian Paolo
GP
D000975:Antioxidants / Q000032:analysis*; D000069059:Atorvastatin; D002374:Catalase / Q000097:blood; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003067:Coenzymes; D004912:Erythrocytes / Q000737:chemistry; D005231:Fatty Acids, Unsaturated / Q000097:blood*; D005978:Glutathione / Q000097:blood; D005979:Glutathione Peroxidase / Q000097:blood; D006538:Heptanoic Acids / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D006949:Hyperlipidemias / Q000188:drug therapy; D008214:Lymphocytes / Q000737:chemistry*; D008297:Male; D008875:Middle Aged; D017035:Pravastatin / Q000009:adverse effects / Q000627:therapeutic use; D011758:Pyrroles / Q000009:adverse effects / Q000627:therapeutic use; D019821:Simvastatin / Q000009:adverse effects / Q000627:therapeutic use; D013482:Superoxide Dismutase / Q000097:blood; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000097:blood*; D014810:Vitamin E / Q000097:blood
D000975:Antioxidants; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D003067:Coenzymes; D005231:Fatty Acids, Unsaturated; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D014451:Ubiquinone; D014810:Vitamin E; D002784:Cholesterol; D000069059:Atorvastatin; D019821:Simvastatin; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; C024989:coenzyme Q10; D005978:Glutathione; D017035:Pravastatin; C003741:ubiquinol