IngentaConnect Lipid-lowering drugs and mitochondrial function: effects of HMG-C...

Authors: DE PINIEUX, G.¹; CHARIOT, P.¹; AMMI-SAÏD, M.²; LOUARN, F.³; LEJONC, J. L.⁴; ASTIER, A.⁵; JACOTOT, B.⁴; GHERARDI, R.¹

Source: British Journal of Clinical Pharmacology, Volume 42, Number 3, September 1996 , pp. 333-337(5)

Publisher: Blackwell Publishing

Abstract:

1Statins inhibit synthesis of mevalonate, a precursor of ubiquinone that is a central compound of the mitochondrial respiratory chain. The main adverse effect of statins is a toxic myopathy possibly related to mitochondrial dysfunction.

2This study was designed to evaluate the effect of lipid-lowering drugs on ubiquinone (coenzyme Q10) serum level and on mitochondrial function assessed by blood lactate/pyruvate ratio.

3Eighty hypercholesterolaemic patients (40 treated by statins, 20 treated by fibrates, and 20 untreated patients, all 80 having total cholesterol levels >6.0 mmol l⁻¹) and 20 healthy controls were included. Ubiquinone serum level and blood lactate/pyruvate ratio used as a test for mitochondrial dysfunction were evaluated in all subjects.

4Lactate/pyruvate ratios were significantly higher in patients treated by statins than in untreated hypercholesterolaemic patients or in healthy controls (P<0.05 and P<0.001). The difference was not significant between fibrate-treated patients and untreated patients.

5Ubiquinone serum levels were lower in statin-treated patients (0.75 mg l⁻¹±0.04) than in untreated hypercholesterolaemic patients (0.95 mg l⁻¹±0.09; P<0.05).

6We conclude that statin therapy can be associated with high blood lactate/pyruvate ratio suggestive of mitochondrial dysfunction. It is uncertain to what extent low serum levels of ubiquinone could explain the mitochondrial dysfunction.

Keywords: statins; fibrates; hypercholesterolaemia; ubiquinone; lactate; mitochondria

Document Type: Research article

DOI: 10.1046/j.1365-2125.1996.04178.x

Affiliations: 1: Groupe de Recherche en Pathologie Neuromusculaire (ER 269), Faculté de Médecine de Créteil, Departments of, 2: Physiology, 3: Neurology, Hôpital Albert Chenevier, Créteil, France 4: Internal Medicine, Hôpital Henri Mondor, Créteil and Department of, 5: Toxicology,

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Lipid-lowering drugs and mitochondrial function: effects of HMG-CoA reductase inhibitors on serum ubiquinone and blood lactate/pyruvate ratio