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R.J. Cenedella, A.R. Neely, P.S. Sexton; Concentration and Distribution of Coenzyme Q (Ubiquinone), the Natural Lipid Antioxidant, in Rat Lens: Effect of Treatment With Simvastatin . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3866.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose:Coenzyme Q is a component of the electron transport chain and a free radical scavenger (antioxidant). It is the only known endogenously formed lipid–soluble antioxidant in tissues. It is formed from farnesyl pyrophoshate, an intermediate in the cholesterol synthesis pathway. There are no reports on coenzyme Q (CoQ) in the lens. Our goals were to measure CoQ concentration and distribution in the rat lens and to determine if treatment of rats with the cholesterol synthesis inhibitor simvastatin (Zocor) altered lens CoQ levels. Methods: Simvastatin induces cataracts in Chbb: Thom but not Sprague Dawley rats (Cenedella et al, J. Lipid Research , 44, 198–211, 2003). Intact lenses and lens regions (epithelium, cortex , nucleus) from control and treated rats (36 days old–treated 16 days, 200 mg/Kg) were homogenized in 1 ml of 0.25 M sucrose plus 18 ml of methanol. Ten µg of CoQ6 ,6 isoprene side chain, were added as internal standard. Ubiquinones were extracted with 12 ml of pet ether, the ether evaporated, and the residue dissolved in 110 µl of ethanol. CoQ9 and 10 were quantitated by HPLC (Waters, Spherisorb ODS–2–5µm, 150 x 3.2 mm column run at 1ml/min–70:30 methanol:ethanol and monitored at 275 nm). Results: CoQ9, 9 isoprenes, is the main ubiquinone in rat tissues. Intact lens contained 2–3 µg of CoQ/g wet lens of which about 80 % was CoQ9. Rat liver, by contrast, contained 40–50 µg/g. The lens epithelium fraction contained 7–8 µg/g. However, the epithelium accounted for only a small portion of the total CoQ in the lens (about 7 ng/lens versus about 18 ng and 37 ng per lens cortex and nucleus, respectively). About 75% of the lens CoQ appeared membrane associated. Treatment with simvastatin tended to decrease lens levels of CoQ, by about 20%, in both rat strains. The decrease became statistically significant when the data for the treated rat groups were pooled. Conclusions: The rat lens contains measurable amounts of the antioxidant Coenzyme Q, being mainly CoQ9. The higher concentration of CoQ in the epithelium than cortex or nucleus likely reflects the greater abundance of mitochondria in this fraction. However, most of the lens CoQ is present in cortical and nuclear membranes were it may provide protection against oxidation of membrane lipids. The modest decrease in lens CoQ levels in simvastatin treated rats might reflect a response to oxidative insult.
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