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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
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신경세포의 Myelination에 있어서 Myelin Basic Protein의 Methyl화 현상에 관한 연구
이향우,전재광 대한약학회 1987 약학회지 Vol.31 No.5
It is reasonably well known that there is a relationship between myelin formation and methylation of myelin basic protein in nerve cells. One of the suggestions is that arginine methylation of myelin basic protein could be of aid in the conjugation of myelin protein with the nonpolar lipid to form myelin. Abnormality in methylation of myclin basic protein might induce the neurological diseases in experimental animals as well as in human being. In the biological system, the methylation reaction is catalyzed by protein methaylse I using S-adenosyl-L-methionine as methyl donor. In this study, we examined the changes of S-adenosyl-L-methionine concentration and protein methylase I activity in developing rat brain tissues. The results are sumraerized as followings: (1) In brain tissues of fetus rat, the concentration of S-adenosyl-L-methionine was gradually decreased until to birth. However, the concentration in brain tissues of infant rat was suddenly increased at 7th day(just before myelination occur) birth. (2) Protein methylase I activity was decreased until to birth in brain of fetus rat and increased temporally just after birth, However, the enzyme activity showed no changes around 7th day after birth.
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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.
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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.
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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.
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담즙분비와 Cyclic nucleotides간의 상호관계에 관한 연구
이향우,김원준,홍사석,조석준,홍사오,임중기,Lee, H.W.,Kim, W.J.,Hong, S.S.,Cho, S.J.,Hong, S.U.,Lim, C.K. 대한약리학회 1982 대한약리학잡지 Vol.18 No.1
Bile formation is a complex process comprised of three separate physiologic mechanism operating at two anatomical sites. At present time, it was known that at least two processes are responsible for total canalicular secretion at the bile canaliculus. One of the processes is bile salt-dependent secretion (BSDS) hypothesis that the active transport of bile salts from plasma to bile provided a primary stimulus for bile formation: the osmotic effect of actively transported bile acid was responsible for the movement of water and ions into bile. The other process is bile salt-independent secretion (ESIS), which is unrelated to bile salt secretion at the canaliculus and which may involve the active transport of sodium. The third process for bile formation involves the biliary ductal epithelium. Secretin-stimulated bile characteristically contained bicarbonate in high concentration. Therefor, it was suggested that secretin stimulated water and bicarbonate secretion from the biliary ductules. One the other hand, it was found that a large amounts of cAMP was present in canine bile but no apparent relationship between bile salt secretion and cAMP content in dog bile. However, bile flow studies in human have demonstrated that secretin and glucagon increase bile cAMP secretion as does secretin in baboons. Secretin increases baboon bile duct mucosal cAMP levels in addition to bile CAMP levels suggesting that in that species secretin-stimulated bile flow may be cAMP mediated. It has been postulated that glucagon and theophylline which increase the bile salt-independent secretion in dogs might act through an increased in liver cAMP content. In a few studies, the possible role of cAMP on bile formation has teen tested by administration of an exogenous derivative of cAMP, dibutyryl cAMP. In the rat, DB cAMP did not modify bile flow, but injection of DB cAMP in the dog promoted an increase in the bile salt-independent secretion. Because of these contradictory results, this study was carried out to examine the relationship between cyclic nucleotides and bile flow due to various bile salts as well as secretin or theophylline. Experiments were performed in rabbits with anesthesia produced by the injection of seconal(30 mg/kg). Rabbits had the cystic duct ligated and the proximal end of the divided common duct cannulated with an appropriately sized polyethylene catheter. A similar catheter was placed into the inferior vena cava for administration of drugs. Bile was collected for determination of cyclic nucleotides and total cholate in 15 min. intervals for a few hours. The results are summerized as followings. 1) Administrations of taurocholic acid or chenodeoxycholic acid increased significantly the concentrations of cAMP and cGMP in bile of rabbits. 2) Concentration of cAMP in bile during the continuous infusion of ursodeoxycholic acid, was remarkedly increased in accordance with the increase of bile flow, while on the contrary concentration of cGMP in bile was decreased significantly. 3) Dehydrocholic acid and deoxycholic acid significantly increased bile flow, total cholate output and cyclic nucleotides in bile. 4) Only cAMP concentration in bile was significantly increased from control value by secretin, while theophylline increased cAMP as well as cGMP in rabbit bile. 5) In addition, the administration of secretin to taurocholic acid-stimulated bile flow increased cAMP while theophylline produced the increases of cAMP and cGMP in bile. 6) The administration of insulin to taurocholic acid-stimulated bile flow decreased cAMP concentration, while on the contrary cGMP was remarkedly increased in rabbit bile.
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올리고머형 음이온성계면활성제 수용액에서 안료의 분산안정성 3 : 형광성이 큰 올리고머 계면활성제의 합성 및 그의 계면성
이향우,이진희,주명종,남기대 한국유화학회 1997 한국응용과학기술학회지 Vol.14 No.1
Fluorescent anionic oligo surfactants were synthesized by the condensing products of long chain alkylvinylether-maleic anhydride cooligomers and resorcinol including dye structures. Their various surface activities and dispersing action were studied on the aqueous solution. These oligo surfactants exhibited a remarkable surface tension lowering property, lower foaming and a large dispersing action for the particles of α-copper phthalocyanine blue. Further it was ascertained that the binding of oligo surfactant onto the pigment surface caused the deviation towards lower wavelengths at the maximum fluorescent intensity as compared with aqueous oligo surfactant solutions, These surface active properties of the oligo surfactants may be attributed to rigid and hydrophobic structure of dye groups, besides surface-active groups of alkylether groups and carboxylic group of the anionic oligo surfactants.
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