Riboflavin Tetrabutylate가 약물대사 효소 및 지질 과산화효소에 미치는 영향

이향우,김원준,홍사석,곽창열,홍사오 大韓藥理學會 1980 대한약리학잡지 Vol.16 No.2

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 <TEX>$CCl_4$</TEX>. It is now reasonably established that <TEX>$CCl_4$</TEX> 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 <TEX>$CCl_4$</TEX>. 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 <TEX>$P_{450}$</TEX>. However, the presence of an antioxidant prevented lipid peroxidation and preserved cytochrome <TEX>$P_{450}$</TEX>. Decrease of cytochrome <TEX>$P_{450}$</TEX> in microsomes under in vitro incubation can be enhanced by <TEX>$CCl_4</TEX> and these changes were parallel to a loss of microsomal polyunsaturated fatty acid and formation of malonaldehyde. The primary purpose of this experiment was to study the effect of riboflavin tetrabutylate on lipid peroxidation, specially, the relationship between lipid peroxidation and drug metabolizing enzyme system which is located in smooth endoplasmic recticulum as well as the effect of ritoflavin tetrabutylate on drug metabolizing enzyme system of animal treated with <TEX>$CCl_4$</TEX>. Albino rats were used for experimental animal. In order to induce drug metabolizing enzyme system, phenobarbital was injected intraperitoneally. <TEX>$CCl_$</TEX> and riboflavin tetrabutylate were given intraperitoneally as solution in olive oil. Microsomal fraction was isolated from

주목받는 沮害劑 개발 : 癌?심혈관?백내장치료제등 다양

李香雨 약사공론 1992 대한약사회지 Vol.1992 No.1

방사 및 열처리 조건에 따른 PEN fiber 의 구조 및 물성 변화

노향우,옥영숙,송기봉 한국고분자학회 1996 한국고분자학회 학술대회 연구논문 초록집 Vol.1996 No.10

Blood Compatibility of Hydrophilic Polyurethane and Hydrophobic Polystyrene IPNs

노향우,김성철 한국고분자학회 1994 한국고분자학회 학술대회 연구논문 초록집 Vol.1994 No.10

초록집 ( 1993 . 4 . 15 ) : 1993 년도 신약개발 연구결과 / 미발표 결과 목차 ; Transmethylase 억제제 ( TMI ) 의 활성 및 작용기전 연구개발

이향우 한국응용약물학회 1993 학술대회 Vol.1993 No.1

타이어공장 근로자 수근관증후군의 업무관련성 조사 사례: 노출평가

류향우(H-W Ryu),박정근(J-K Park),정윤경(Y-K Chung),한영선(Y-S Han),장승희(S-H Chang) 대한인간공학회 2015 대한인간공학회 학술대회논문집 Vol.2015 No.10

비타민 A 및 $B_2$ 유도체의 Aminopyrine Demethylase 활성도에 대한 영향

이향우 대한약학회 1984 약학회지 Vol.28 No.1

Drug-metabolizing system which has the important role in drug metabolism is localized in smooth endoplasmic reticulum of hepatocytes and is composed of NADPH, NADPH-cytochrome $P_{450}$ reductase, cytochrome $P_{450}$ and others. It is well known that the enzyme system is induced by phenobarbital and methylcholanthrene. Lipid peroxidation is reaction of oxidative deterioration of polyunsaturated lipids. Formation of lipid peroxides in liver microsome has been found to produce degradation of phospholipid, which are major components of microsomal membrane. The relationship between the formation of lipid oxides and the activities of drug-metabolizing enzyme in the liver of rats was reported by several investigators. In this study the effect of riboflavin tetrabutylate, an antioxidant on lipid peroxidation, specially the relationship between lipid peroxidation and drug-metabolizing enzyme system was investigated. In addition the effect of vitamin A derivatives, such as retinoic acid and retinoid on the enzyme was also observed. Results are summarized as followings. 1) The pretretment with riboflavin tetrabutylate inhibited completely the lengthened sleeping time due to $CCl_{4}$ treatment. 2) The increase of TBA value was prevented by the pretreatment with riboflavin tetrabutylate. 3) The pretreatment with riboflavin tetrabutylate also prevented the decrease of drug-metabolizing enzyme caused by $CCl_{4}$. 4) Both retinoic acid and retinoid remarkably decreased the activity of aminopyrine demethylase. Pretreatment of riboflavin tetrabutylate, however, prevented inhibitory effect of retinoic acid on the enzyme activity.

膵組織 Protein Methylases 活性에 대한 Nicotine의 影響

李香雨,李秀英 成均館大學校 科學技術硏究所 1986 論文集 Vol.37 No.1

It has been known for some time that tobacco smoke or nicotine affects exocrine function of pancreas. Edmund et al. reported that nicotine inhibited pancreatic secretion stimulated by secretin. Furthermore, Solomon et al. have demonstrated that nicotine inhibits the flow of the juice and bicarbonate output. Recently, Majumdar et al. have investigated that the in vitro effect of nicotine on the synthesis and secretion of proteins in dispersed rat pancreatic acini in viro. It was concluded that nicotine stimulated the secretion of preformed zymogen granules and newly sythesized proteins from dispered rat pancreatic acini in vitro. On the other hand, there are many reports that suggest the relationship between protein methylation and pancreatic secretion. Specifically, protein carboxymethylation is involved in arnylase secretion of parotid gland by isoproterenol as well as in pancreatic enzyme secretion. Therefore, in this study we have investigated the effect of nicotine on the activities of protein methylases as well as on pancreatic enzymes in vitro. The following results were obtained; 1) In the presence of 8mM nicotine the secretion of amylase was greatly stimulated from the isolated pancreatic fragments. however, this stimulatory effect of nicotine was inhibited by 2.5mM of cycloheximide. 2) In the case of protein methylase activity, nicotine exhibited the profound stimulation of protein methylase Ⅱ and Ⅲ activity. In the presence of 8mM nicotine, the protein methylase Ⅱ and Ⅲ were stimulated by 3 and 2 folds, respectively, when compared with the corresponding control. This profound increment were blocked by 2.5mM cycloheximide.

취외분비에 미치는 cyclic nucleotides의 역할

이향우,김원준,홍사석,Lee, H.W.,Kim, W.J.,Hong, S.S. 대한약리학회 1977 대한약리학잡지 Vol.13 No.2

In 1968, Case et al. first studied the importance of cyclic AMP as an intermediate in the action of secretin and cholecystokinin-pancreozymin and they suggested that the action of secretin, not that of cholecystokinin-pancreozymin, may be mediated through cyclic AMP. Recently Albano et al. reported that in the exocrine pancreas each of the two major physiological functions is modulated a specific cyclic nucleotide, enzyme secretion by cyclic GMP, and fluid and ionic secretion by cyclic AMP. But in pancreas still conflicting results have been reported on the role of cyclic nucleotides in enzyme and electrolyte secretion. In these study, the role of cyclic nucleotides in the exocrine pancreatic secretion was examined. The results are as follows. 1) Very strong stimulation on amylase release from guinea pig pancreatic slice was produced by 1 unit of cholecystokinin-pancreozymin but as compared to that of cholecystokinin-pancreozymin very weak response was observed by 1 unit of secretion or $1\;{\mu}g$ of VIP. 2) Both cholecystokinin-pancreozymin and acetylcholine produced a rapid and marked rise in cyclic GMP as well as cyclic AMP in isolated pancreatic tissue. However, both secretin and VIP failed to alter significantly the basal level of cyclic GMP in pancreatic fragments. 3) Atropine inhibited acetylcholine mediated amylase release, but did not affect the cholecystokinin-pancreozymin response. Furthermore, atropine pretreatment produced a marked inhibitory effect on the increase of tissue cyclic nucleotides induced by cholecystokinin-pancreozymin and acetylcholine. In summary, these results suggest that whereas the pancreatic secretion produced by secretin and VIP is modulated by the formation of cyclic AMP, the pancreatic enzyme secretion in response to cholecystokinin-pancreozymin and acetylcholine is triggered by both cyclic AMP and cyclic GMP.

Vitamin A 유도체로 인한 간의 약물대사효소 변동

이향우,유경자,노재열,홍사석,Lee, H.W.,Ryu, K.Z.,Ro, J.Y.,Hong, S.S. 대한약리학회 1982 대한약리학잡지 Vol.18 No.1

It has been known that retinoids are intrinsically of critical importance for control of premalignant epithelial cell differentiation. In the absence of retinoids, normal cellular differentiation and growth does not occur in epithelia such as those of trachea and bronchi. Furthermore, it was also reported that retinoid deficiency enhanced susceptibility to chemical carcinogenesis in the respiratory system, in the bladder, and in the colon of the experimental animal. In 1974, Bollag examined the effects of synthetic retinoids in prevention of development of cancer and demonstrated synthetic retinoids to have more favorable therapeutic index than retinoic acid for causing regression of skin papilloma in mice. Therefore, it was assumed that this anticarcinogenic effect of vitamin A derivatives could be due to modification of the metabolism of the carcinogenic polycyclic hydrocarbon, which must first be activated to exert their effect. Hill and Shih reported that vitamin A compounds and analogs had inhibitory effect on drug metabolizing enzyme from liver and lung tissue of mouse and hamster. Lucy suggested that the chemoprevention effect of vitamin A derivatives is due to reaction with molecular oxygen, and it is possible that inhibition of hydroxybenzpyrene formation is a result of this property. On the other hand, butylated hydroxytoluene which is a potent antioxidant strongly inhibited the formation of mammary tumor induced by dimethylbenranthracene. Also, it was observed that this antioxidant inhibited cancer induction in rats by N-2-fluo-renylacetamide. The purpose of this experiment was to investigate the effect of vitamin A derivatives such as retinoic acid and retinoid on drug-metabolizing enzyme and to determine whether riboflavin tetrabutylate or vitamin E could prevent of modify any changes induced by vitamin A delivatives in the rats. The results obtained were as followings. 1) Body weight was significantly reduced by retinoic acid, but not by retinoid. 2) Retinoic acid markedly increased liver weight while retincid showed no effect on liver weight. Treatment of riboflavin tetrabutylate did not affect retinoic acid-induced change in both body weight and liver weight. 3) Both retinoic acid and retinoid remarkably decreased the activity of aminopyrine demethylase. Pretreatment of riboflavin tetrabutylate, however, prevented inhibitory effect of retinoic acid on the enzyme activity. 4) No significant effect of vitamin E on aminopyrine demethylase was observed in both groups treated with retinoic acid and retinoid.