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乙醇、洛伐他汀和辅酶Q10处理对大鼠肝脏抗氧化剂及TBA反应性物质的影响。

Effects of ethanol, lovastatin and coenzyme Q10 treatment on antioxidants and TBA reactive material in liver of rats.

作者信息

Loop R A, Anthony M, Willis R A, Folkers K

机构信息

Graduate Program in Nutritional Sciences, University of Texas, Austin 78712, USA.

出版信息

Mol Aspects Med. 1994;15 Suppl:s195-206. doi: 10.1016/0098-2997(94)90029-9.

Abstract

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.

摘要

酒精代谢可能通过多种机制导致氧化应激和自由基损伤。洛伐他汀也可能通过降低内源性抗氧化剂辅酶Q(CoQ)的水平而产生氧化应激。研究了在大鼠全液体饮食中20 EN%的乙醇和67 mg/kg饮食的洛伐他汀单独及联合作用对大鼠肝脏中α-生育酚、视黄醇棕榈酸酯、CoQ9和硫代巴比妥酸反应性(TBAR)物质的影响。还测定了外源性CoQ10对这些治疗组的作用。各治疗组之间的食物摄入量、体重增加、肝脏脂质和TBAR物质相似。与对照动物相比,乙醇使视黄醇棕榈酸酯显著降低,从143微克/克湿重降至90微克/克湿重。洛伐他汀对视黄醇棕榈酸酯无影响,也不与乙醇产生相加作用。乙醇使肝脏α-生育酚从28微克/克湿重降至12微克/克湿重,洛伐他汀使其降至12微克;未观察到相加作用。乙醇无影响,但洛伐他汀使CoQ9从83微克/克湿重降至55微克/克湿重。补充CoQ10未调节乙醇对视黄醇棕榈酸酯的作用,但确实逆转了洛伐他汀对CoQ9的作用。补充CoQ10未改变α-生育酚的对照水平,但似乎逆转了大部分分别由乙醇或洛伐他汀导致的α-生育酚降低。然而,它仅部分逆转了乙醇和洛伐他汀联合对α-生育酚的作用。正如预期的那样,洛伐他汀对补充动物的CoQ10水平无影响。乙醇单独或与洛伐他汀联合使用,使肝脏CoQ10储备减少近40%。我们得出结论,在液体饮食中给予20 EN%的乙醇5周足以降低视黄醇棕榈酸酯,洛伐他汀可降低CoQ9。两者均降低α-生育酚,单独使用任何一种药物补充CoQ10在很大程度上可克服这种作用,但联合使用时则不然。由于许多人长期摄入本实验中所代表的乙醇水平,并且其中一定数量的人也服用洛伐他汀,因此有必要进一步研究这些观察结果可能的临床意义。

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