Effects of ethanol, lovastatin and coenzyme Q10 treatment on antioxidants and TBA reactive material in liver of rats.
Alcohol metabolism may result in oxidant stress and free radical injury through a variety of mechanisms. Lovastatin may also produce oxidant stress by reducing levels of an endogenous antioxidant, coenzyme Q (CoQ). The separate and combined effects of ethanol, 20 EN% in a total liquid diet, and lovastatin, 67 mg/kg diet, on alpha-tocopherol, retinol palmitate, CoQ9 and thiobarbituric acid reactive (TBAR) material in liver from rats were determined. The effect of exogenous CoQ10 on these treatment groups was also determined. Food consumption, weight gain, liver lipid and TBAR material were similar between treatment groups. Compared to control animals, ethanol reduced retinol palmitate significantly, from 143 to 90 micrograms/g wet weight. Lovastatin had no effect on retinal palmitate nor did it act additively with ethanol. Ethanol decreased liver alpha-tocopherol from 28 to 12 micrograms/g wet weight and lovastatin diminished it to 12 micrograms; no additive effect was evident. Ethanol had no effect, but lovastatin decreased CoQ9 from 83 to 55 micrograms/g wet weight. Supplementation with CoQ10 did not modulate the effect of ethanol on retinal palmitate, but it did reverse the effect of lovastatin on CoQ9. Supplementary CoQ10 did not alter control levels of alpha-tocopherol, but it appeared to reverse most of the decrease in alpha-tocopherol attributable to ethanol or lovastatin separately. It only partially reversed the effect of ethanol and lovastatin combined on alpha-tocopherol, however. As expected, lovastatin had no effect on CoQ10 levels in supplemented animals. Ethanol, either separately or in combination with lovastatin, diminished liver stores of CoQ10 by almost 40%. We conclude that 20 EN% ethanol given in a liquid diet for 5 weeks is sufficient to lower retinol palmitate and that lovastatin reduces CoQ9. Both diminish alpha-tocopherol, an effect largely overcome by CoQ10 supplementation with either drug alone, but not with the combination. Since many individuals chronically consume the levels of ethanol represented by this experiment, and since a certain number of those also take lovastatin, further research into the possible clinical significance of these observations is warranted.
Loop
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Graduate Program in Nutritional Sciences, University of Texas, Austin 78712, USA.
Anthony
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Willis
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Folkers
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K
D000818:Animals; D000975:Antioxidants / Q000032:analysis*; D001835:Body Weight / Q000187:drug effects; D003067:Coenzymes; D004032:Diet; D004224:Diterpenes; D004353:Drug Evaluation, Preclinical; D000431:Ethanol / Q000494:pharmacology* / Q000633:toxicity; D008099:Liver / Q000737:chemistry / Q000187:drug effects*; D008108:Liver Diseases, Alcoholic / Q000517:prevention & control; D008148:Lovastatin / Q000494:pharmacology* / Q000633:toxicity; D009929:Organ Size / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D000084562:Retinyl Esters; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis*; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000032:analysis / Q000494:pharmacology; D014801:Vitamin A / Q000031:analogs & derivatives / Q000032:analysis; D014810:Vitamin E / Q000032:analysis
D000975:Antioxidants; D003067:Coenzymes; D004224:Diterpenes; D000084562:Retinyl Esters; D017392:Thiobarbituric Acid Reactive Substances; D014801:Vitamin A; D014451:Ubiquinone; D014810:Vitamin E; C014794:retinol palmitate; D000431:Ethanol; D008148:Lovastatin; C024989:coenzyme Q10; C030571:ubiquinone 9