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KMID : 0360419800160020045
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Korean Journal of Pharmacology
1980 Volume.16 No. 2 p.45 ~ p.53
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Effect of Riboflavin Tetrabutylate on the Activity of Drug Metabolizing Enzyme and Lipid Peroxidation in Liver Microsomes of Rats
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李香雨/Lee, H.W.
金源准/洪思奭/郭昌烈/洪思澳/Kim W.J./Hong, S.S./Kwack, C.Y./Hong, S.U.
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Abstract
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Lipid peroxidation in vitro has been identified as a basic deteriorative reaction in cellular mechanism of aging processes, such as air pollution oxidant damage to cell and to the lung, chlorinated hydrocarbon hepatotoxicity.
Many experimental evidences were reported by several investigators that lipid peroxidation could be one of the principle causes for the hepatotoxicity produced by CCl₄. It is now reasonably established that CCl₄ is activated to a free radical in vivo, that lipid peroxidation occurs very quickly in microsomes prepared from damaged livers, that the peroxidation is associated with loss of enzyme activity of microsomes, and that various antioxidants can protect animals against the hepatotoxic effect of CCl₄.
Recent studies have drawn attention to some other feature of microsomal lipid peroxidation. Incubation of liver microsomes in the presence of NADPH has led to a loss of cytochrome P_(450). However, the presence of an antioxidant prevented lipid peroxidation and preserved cytochrome P_(450). Decrease of cytochrome P_(450) in microsomes under in vitro incubation can be enhanced by CCl₄ and these changes were parallel to a loss of microsomal polyunsaturated fatty acid and formation of malonaldehyde.
The primary purpose of this experiment was to study the effect of riboflavin tetrabutylate on lipid peroxidation, specially, the relationship between lipid peroxidation and drug metabolizing enzyme system which is located in smooth endoplasmic recticulum as well as the effect of ritoflavin tetrabutylate on drug metabolizing enzyme system of animal treated with CCl₄.
Albino rats were used for experimental animal. In order to induce drug metabolizing enzyme system, phenobarbital was injected intraperitoneally. CCl₄ and riboflavin tetrabutylate were given intraperitoneally as solution in olive oil. Microsomal fraction was isolated from liver of animals and TBA value as well as the activity of drug metabolizing enzyme were measured in the microsomal fractions.
The results are summerized as following.
1) The secobarbital induced sleeping time of CCl₄ treated rat was about 2 times longer than that of the control group. However, the pretreatment with riboflavin tetrabutylate inhibited completely the lengthened sleeping time due to CCl₄ treatment. Furthermore TBA value was significantly increased in CCl₄ treated rat in comparison to control group tut the increase of TBA value was prevented by the pretreatment with riboflavin tetrabutylate. On the other hand, the activity of hepatic drug metabolizing enzyme was decreased in CCl₄ group, however, the pretreatment with riboflavin tetrabutylate also prevented the decrease of the enzyme activity caused by CCl₄.
2) The effect of riboflavin tetrabutylate on TBA value and the activity of drug metabolizing enzyme in vitro was similar to in vivo results. Incubation of liver microsome from rat in the presence of CCl₄, Fe^(++), or ascorbic acid has led to the marked increase of TBA value, however, the addition of riboflavin tetrabutylate in incubation mixture prevented significantly the increase of TBA value, suggesting the inhibition of lipid peroxidation. In accordance with TBA value, the activity of drug metabolizing enzyme was inhibited in the presence of CCl₄, Fe^(++), ascorbic acid but the addition of riboflavin tetrabutylate protected the loss of the enzyme activity in microsome under in vitro incubation.
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