Concentration and distribution of ubiquinone (coenzyme Q), the endogenous lipid antioxidant, in the rat lens: effect of treatment with simvastatin.
OBJECTIVE
Ubiquinone (Ub) is the only known endogenously synthesized lipid soluble antioxidant. It is synthesized from intermediates in the cholesterol metabolic pathway. Our goal was to identify the Ubs and determine the concentration and distribution of Ubs in the rat lens and the effect of treatment with simvastatin, a cholesterol synthesis inhibitor, on lens levels.


METHODS
Intact lenses and separated lens fractions from young rats were homogenized in organic solvents, the Ubs recovered, and identified by HPLC analysis. Rats were fed Ub-10 to determine effects of supplementation on tissue levels. Sprague-Dawley (SD) and Chbb:Thom (CT) rats were treated with simvastatin, an inducer of cataracts in CT rats, to determine its effects on lens Ubs.


RESULTS
Ubiquinone-9 (9 isoprenes in its hydrocarbon tail) was the main Ub in the rat lens. The intact lens contained about 3.0 microg Ub/g lens wet weight of which 80-90% was Ub-9 and the remainder Ub-10. No reduced Ubs were detected. Although the epithelial fraction contained the highest Ub concentration (about 8 microg/g), the cortex and nucleus combined accounted for about 90% of the lens' total content. Dietary supplementation with Ub-10 markedly increased the Ub-10 concentration in liver but not lens. Treatment with simvastatin decreased lens Ubs of both SD and CT rats by about 20%.


CONCLUSIONS
The abundance of mitochondria in lens epithelium likely accounted for its high level of Ubs; but, finding most of the lens' total Ub in the cortex plus nucleus also suggests roles in maintaining the fiber cell membrane. The decrease in lens Ubs caused by simvastatin is interpreted to reflect a response to drug induced cellular stress rather than to inhibition of the cholesterol synthesis pathway.
Cenedella
Richard J
RJ
Department of Biochemistry, Kirksville College of Osteopathic Medicine, Kirksville, MO 63501, USA. rcenedella@atsu.edu
Neely
Amanda R
AR
Sexton
Patricia
P
D000293:Adolescent; D000368:Aged; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007908:Lens, Crystalline / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D008875:Middle Aged; D010084:Oxidation-Reduction; D051381:Rats; D011922:Rats, Mutant Strains; D017207:Rats, Sprague-Dawley; D019821:Simvastatin / Q000494:pharmacology*; D014451:Ubiquinone / Q000378:metabolism*
D000975:Antioxidants; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014451:Ubiquinone; D019821:Simvastatin