Pub Date : 2001-01-01DOI: 10.1515/DMDI.2001.18.1.33
I. Stoilov, I. Jansson, M. Sarfarazi, J. Schenkman
Cytochrome P450 (CYP) forms are ubiquitous in nature, appearing in almost all phyla, with many forms appearing in any organism. About 50 different forms have been identified in man, and some of these are found in the embryo, some showing temporal dependence. Many of the forms of cytochrome P450 present in one species have homologues in other species. For example, CYP1A2 is present in many species, including man, rabbits, rodents, fish and fowl. The amino acid sequence identity of these homologues is often in excess of 70%. CYP26, too, has more than 61% identity in amino acid sequence between fish, fowl and mammals. In view of the high degree of conservation of sequence as well as of enzymatic activities, it is only reasonable to assume that such strong conservation of sequence also reflects a conservation of function. Since the 'xenobiotic metabolizing' enzymes predate the production of the many xenobiotics they are known to metabolize, perhaps it is reasonable to consider endobiotics as natural substrates for their metabolism. Of the identified forms of cytochrome P450 that are present in embryonic tissue, we consider the possibility that they serve the organism in support of morphogenesis of the embryonic tissue. These forms may either function to generate morphogenic molecules or to keep regions free of them, thereby creating temporal and spatial regions of morphogen action and supporting region-specific changes in cells. One known morphogen, retinoic acid, has the enzymes retinal dehydrogenase (RALDH) and CYP26 maintaining its actions, the former responsible for its generation and the latter for its elimination. Another form of cytochrome P450, CYP1B1 appears also to be involved in differentiation of tissue, with its absence resulting in primary congenital glaucoma. However, the nature of the morphogen it may maintain still remains to be elucidated.
{"title":"Roles of Cytochrome P450 in Development","authors":"I. Stoilov, I. Jansson, M. Sarfarazi, J. Schenkman","doi":"10.1515/DMDI.2001.18.1.33","DOIUrl":"https://doi.org/10.1515/DMDI.2001.18.1.33","url":null,"abstract":"Cytochrome P450 (CYP) forms are ubiquitous in nature, appearing in almost all phyla, with many forms appearing in any organism. About 50 different forms have been identified in man, and some of these are found in the embryo, some showing temporal dependence. Many of the forms of cytochrome P450 present in one species have homologues in other species. For example, CYP1A2 is present in many species, including man, rabbits, rodents, fish and fowl. The amino acid sequence identity of these homologues is often in excess of 70%. CYP26, too, has more than 61% identity in amino acid sequence between fish, fowl and mammals. In view of the high degree of conservation of sequence as well as of enzymatic activities, it is only reasonable to assume that such strong conservation of sequence also reflects a conservation of function. Since the 'xenobiotic metabolizing' enzymes predate the production of the many xenobiotics they are known to metabolize, perhaps it is reasonable to consider endobiotics as natural substrates for their metabolism. Of the identified forms of cytochrome P450 that are present in embryonic tissue, we consider the possibility that they serve the organism in support of morphogenesis of the embryonic tissue. These forms may either function to generate morphogenic molecules or to keep regions free of them, thereby creating temporal and spatial regions of morphogen action and supporting region-specific changes in cells. One known morphogen, retinoic acid, has the enzymes retinal dehydrogenase (RALDH) and CYP26 maintaining its actions, the former responsible for its generation and the latter for its elimination. Another form of cytochrome P450, CYP1B1 appears also to be involved in differentiation of tissue, with its absence resulting in primary congenital glaucoma. However, the nature of the morphogen it may maintain still remains to be elucidated.","PeriodicalId":77889,"journal":{"name":"Reviews on drug metabolism and drug interactions","volume":"18 1","pages":"33 - 56"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/DMDI.2001.18.1.33","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67183336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-01-01DOI: 10.1515/DMDI.2001.18.1.57
B. Vohra, S.P. Sharma, V. Kansal
Age related changes in the mitochondria of different regions of the CNS of two age groups of guinea-pigs (10 months and 32 months) were studied. The activities of glutathione peroxidase (GPx) and glutathione reductase (GRd) decreased significantly (p <0.05) with age in the mitochondrial fractions of cerebral cortex, hypothalamus, cerebellum and spinal cord. A significant (p <0.05) age related decrease in mitochondrial numerical density was observed in all regions studied. Electron microscopic observations revealed various degenerative changes in the mitochondria with age. Treatment of the animals with the Ayurvedic herbal mixture "Maharishi Amrit Kalash" (MAK), 500 mg/kg body wt. daily for 2 months, significantly induced the activity of antioxidant enzymes, and also reversed the pathological changes to a considerable extent. MAK increased the activity of GPx significantly only in the 32 month-old animals. This shows the specificity of the action of MAK.
{"title":"Effect of Maharishi Amrit Kalash on Age Dependent Variations in Mitochondrial Antioxidant Enzymes, Lipid Peroxidation and Mitochondrial Population in Different Regions of the Central Nervous System of Guinea-pigs","authors":"B. Vohra, S.P. Sharma, V. Kansal","doi":"10.1515/DMDI.2001.18.1.57","DOIUrl":"https://doi.org/10.1515/DMDI.2001.18.1.57","url":null,"abstract":"Age related changes in the mitochondria of different regions of the CNS of two age groups of guinea-pigs (10 months and 32 months) were studied. The activities of glutathione peroxidase (GPx) and glutathione reductase (GRd) decreased significantly (p <0.05) with age in the mitochondrial fractions of cerebral cortex, hypothalamus, cerebellum and spinal cord. A significant (p <0.05) age related decrease in mitochondrial numerical density was observed in all regions studied. Electron microscopic observations revealed various degenerative changes in the mitochondria with age. Treatment of the animals with the Ayurvedic herbal mixture \"Maharishi Amrit Kalash\" (MAK), 500 mg/kg body wt. daily for 2 months, significantly induced the activity of antioxidant enzymes, and also reversed the pathological changes to a considerable extent. MAK increased the activity of GPx significantly only in the 32 month-old animals. This shows the specificity of the action of MAK.","PeriodicalId":77889,"journal":{"name":"Reviews on drug metabolism and drug interactions","volume":"18 1","pages":"57 - 68"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/DMDI.2001.18.1.57","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67183400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-01-01DOI: 10.1515/DMDI.2001.18.1.69
G. Uraz, H. Simsek, Y. Maraş
Some Bacillus species are important food pathogens. For example, B. cereus is an opportunistic pathogen found in raw milk that is a common cause of food poisoning. It is of interest to investigate the virulant profiles of Bacillus strains isolated from foods and samples associated with food-poisoning outbreaks. Nineteen Bacillus strains were isolated from various milk samples. Beta-lactamase enzyme activities of these Bacillus strains were evaluated with iodometric and chromogenic cephalosporin (nitrocefin) test methods. Five of 19 Bacillus strains isolated were positive for beta-lactamase activity. Clavulanate-amoxycillin and cephazolin were chosen to test the antibiotic susceptibilities of the beta-lactamase positive and negative Bacillus strains. Of the five beta-lactamase positive Bacillus strains, three were susceptible, and two strains intermediate to clavulanate-amoxycillin; one was susceptible, and four strains were intermediate to cephazolin. None of the beta-lactamase positive Bacillus strains was resistant to both antibiotics. Of the 14 beta-lactamase negative strains, five were susceptible to clavulanate-amoxycillin, four strains were intermediate, and five strains were resistant; three were susceptible, one intermediate, and ten beta-lactamase negative strains were resistant to cephazolin.
{"title":"Determination of β-Lactamase Activities and Antibiotic Susceptibility of Some Bacillus Strains Causing Food Poisoning","authors":"G. Uraz, H. Simsek, Y. Maraş","doi":"10.1515/DMDI.2001.18.1.69","DOIUrl":"https://doi.org/10.1515/DMDI.2001.18.1.69","url":null,"abstract":"Some Bacillus species are important food pathogens. For example, B. cereus is an opportunistic pathogen found in raw milk that is a common cause of food poisoning. It is of interest to investigate the virulant profiles of Bacillus strains isolated from foods and samples associated with food-poisoning outbreaks. Nineteen Bacillus strains were isolated from various milk samples. Beta-lactamase enzyme activities of these Bacillus strains were evaluated with iodometric and chromogenic cephalosporin (nitrocefin) test methods. Five of 19 Bacillus strains isolated were positive for beta-lactamase activity. Clavulanate-amoxycillin and cephazolin were chosen to test the antibiotic susceptibilities of the beta-lactamase positive and negative Bacillus strains. Of the five beta-lactamase positive Bacillus strains, three were susceptible, and two strains intermediate to clavulanate-amoxycillin; one was susceptible, and four strains were intermediate to cephazolin. None of the beta-lactamase positive Bacillus strains was resistant to both antibiotics. Of the 14 beta-lactamase negative strains, five were susceptible to clavulanate-amoxycillin, four strains were intermediate, and five strains were resistant; three were susceptible, one intermediate, and ten beta-lactamase negative strains were resistant to cephazolin.","PeriodicalId":77889,"journal":{"name":"Reviews on drug metabolism and drug interactions","volume":"18 1","pages":"69 - 77"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/DMDI.2001.18.1.69","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67183479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-01-01DOI: 10.1515/DMDI.2001.18.3-4.191
V. Ferranti, C. Chabenat, H. Marchais, S. Ménager, H. Hue, A. Orecchioni, O. Lafont
The aim of this study was to evaluate the influence of primidone (PRM) nanoencapsulation on its metabolism. Suspensions of PRM powder and PRM-loaded poly-epsilon-caprolactone nanocapsules were administered orally in the same way to rats. Primidone-loaded poly-epsilon-caprolactone nanocapsules were prepared according to the interfacial deposition technique. Free PRM suspensions were obtained by addition of PRM powder to a suspension of 0.212% carboxymethylcellulose CMC 12H in water. The dose was 20 mg/kg, n = 6, for each experiment. Urinary and faecal levels of PRM and of its three major metabolites, phenylethylmalonamide (PEMA), phenobarbital (PB), and p-hydroxyphenobarbital (p-HO-PB), were determined. Concentrations were evaluated by high-performance liquid chromatography (HPLC) according to a validated analytical method. After PRM nanocapsule administration, non-metabolised PRM urinary levels were increased compared to those observed after administration of a suspension of primidone powder (43.7+/-8.8% after PRM-loaded nanocapsule and 37.7+/-8.1% after free PRM administration). For phenylethylmalonamide, no difference was observed in urinary excretion in the two cases. For two of the oxidised metabolites, PB and p-HO-PB, excretion was delayed and shortened. The amount of these oxidised metabolites was lowered from 0.95% after free PRM administration to 0.25% after PRM-loaded nanocapsule administration. No difference was noted in non-metabolised primidone excretion in faeces. These results suggest that primidone-loaded nanocapsules could be used as a vehicle for oral primidone administration in order to minimise the phenobarbital metabolic pathway.
本研究的目的是评价primidone (PRM)纳米胶囊化对其代谢的影响。大鼠以相同方式口服PRM粉混悬液和负载PRM的聚ε -己内酯纳米胶囊。采用界面沉积技术制备了负载普米酮的聚ε -己内酯纳米胶囊。将PRM粉末加入到0.212%羧甲基纤维素CMC 12H的悬浮液中，得到游离的PRM悬浮液。每次试验剂量为20 mg/kg, n = 6。测定尿液和粪便中PRM及其三种主要代谢物苯乙基丙二胺(PEMA)、苯巴比妥(PB)和对羟基苯巴比妥(p-HO-PB)的水平。采用高效液相色谱法(HPLC)测定其浓度。服用PRM纳米胶囊后，与服用primidone粉末悬浮液后相比，尿中非代谢PRM水平升高(加载PRM纳米胶囊后为43.7+/-8.8%，自由服用PRM后为37.7+/-8.1%)。对于苯乙基丙二胺，两例患者尿排泄量无差异。对于两种氧化代谢物PB和p-HO-PB，排泄延迟和缩短。这些氧化代谢物的含量从游离给药后的0.95%降低到载药纳米胶囊后的0.25%。粪便中非代谢的primidone排泄量无差异。这些结果表明，载普利米酮纳米胶囊可以作为口服普利米酮的载体，以尽量减少苯巴比妥代谢途径。
{"title":"Effects of Encapsulation of Primidone on its Oxidative Metabolism in Rats","authors":"V. Ferranti, C. Chabenat, H. Marchais, S. Ménager, H. Hue, A. Orecchioni, O. Lafont","doi":"10.1515/DMDI.2001.18.3-4.191","DOIUrl":"https://doi.org/10.1515/DMDI.2001.18.3-4.191","url":null,"abstract":"The aim of this study was to evaluate the influence of primidone (PRM) nanoencapsulation on its metabolism. Suspensions of PRM powder and PRM-loaded poly-epsilon-caprolactone nanocapsules were administered orally in the same way to rats. Primidone-loaded poly-epsilon-caprolactone nanocapsules were prepared according to the interfacial deposition technique. Free PRM suspensions were obtained by addition of PRM powder to a suspension of 0.212% carboxymethylcellulose CMC 12H in water. The dose was 20 mg/kg, n = 6, for each experiment. Urinary and faecal levels of PRM and of its three major metabolites, phenylethylmalonamide (PEMA), phenobarbital (PB), and p-hydroxyphenobarbital (p-HO-PB), were determined. Concentrations were evaluated by high-performance liquid chromatography (HPLC) according to a validated analytical method. After PRM nanocapsule administration, non-metabolised PRM urinary levels were increased compared to those observed after administration of a suspension of primidone powder (43.7+/-8.8% after PRM-loaded nanocapsule and 37.7+/-8.1% after free PRM administration). For phenylethylmalonamide, no difference was observed in urinary excretion in the two cases. For two of the oxidised metabolites, PB and p-HO-PB, excretion was delayed and shortened. The amount of these oxidised metabolites was lowered from 0.95% after free PRM administration to 0.25% after PRM-loaded nanocapsule administration. No difference was noted in non-metabolised primidone excretion in faeces. These results suggest that primidone-loaded nanocapsules could be used as a vehicle for oral primidone administration in order to minimise the phenobarbital metabolic pathway.","PeriodicalId":77889,"journal":{"name":"Reviews on drug metabolism and drug interactions","volume":"18 1","pages":"191 - 208"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/DMDI.2001.18.3-4.191","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67183828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-01-01DOI: 10.1515/DMDI.2001.18.2.149
L. Rao, L.J.-F. Liu,, T. Murray, E. McDermott
It is now well established that estrogen inhibits bone resorption. However, its effect on bone formation remains controversial. We studied the effect of 17beta-estradiol (E2) on mineralized bone nodule formation in long-term cultures of osteosarcoma SaOS-2 cells. We showed that SaOS-2 cells formed mineralized nodules which under electron microscopy revealed a bone structure with active osteoblasts, entrapped osteocytes, extracellular collagen fibrils and hydroxyapatite deposits, making this system a valid model to study bone formation in vitro. Intermittent addition of E2 for 6 hours during a 48-hour cycle of changes of medium, starting from day 3, resulted in a dose-dependent stimulation of mineralized bone nodule number and area, as well as alkaline phosphatase activity. In conclusion, we report for the first time a stimulatory effect of E2 on mineralized bone nodule formation in human osteoblasts in culture.
{"title":"17β-Estradiol Stimulates Mineralized Bone Nodule Formation when Added Intermittently to SaOS-2 Cells","authors":"L. Rao, L.J.-F. Liu,, T. Murray, E. McDermott","doi":"10.1515/DMDI.2001.18.2.149","DOIUrl":"https://doi.org/10.1515/DMDI.2001.18.2.149","url":null,"abstract":"It is now well established that estrogen inhibits bone resorption. However, its effect on bone formation remains controversial. We studied the effect of 17beta-estradiol (E2) on mineralized bone nodule formation in long-term cultures of osteosarcoma SaOS-2 cells. We showed that SaOS-2 cells formed mineralized nodules which under electron microscopy revealed a bone structure with active osteoblasts, entrapped osteocytes, extracellular collagen fibrils and hydroxyapatite deposits, making this system a valid model to study bone formation in vitro. Intermittent addition of E2 for 6 hours during a 48-hour cycle of changes of medium, starting from day 3, resulted in a dose-dependent stimulation of mineralized bone nodule number and area, as well as alkaline phosphatase activity. In conclusion, we report for the first time a stimulatory effect of E2 on mineralized bone nodule formation in human osteoblasts in culture.","PeriodicalId":77889,"journal":{"name":"Reviews on drug metabolism and drug interactions","volume":"121 1","pages":"149 - 158"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/DMDI.2001.18.2.149","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67184086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-01-01DOI: 10.1515/dmdi.2001.18.3-4.159
M Afzal, D Al-Hadidi, M Menon, J Pesek, M S Dhami
Powerful medicinal properties have been recorded for Zingiber officinale, commonly known as ginger. All of these medicinal activities have been compiled with 99 references to the present status of the plant in the literature. Volatile components and the presence of trace metals are included. In addition, details of individual medicinal activities are given and the molecular structures of identified organic metabolites and their synthesis are described.
{"title":"Ginger: an ethnomedical, chemical and pharmacological review.","authors":"M Afzal, D Al-Hadidi, M Menon, J Pesek, M S Dhami","doi":"10.1515/dmdi.2001.18.3-4.159","DOIUrl":"10.1515/dmdi.2001.18.3-4.159","url":null,"abstract":"<p><p>Powerful medicinal properties have been recorded for Zingiber officinale, commonly known as ginger. All of these medicinal activities have been compiled with 99 references to the present status of the plant in the literature. Volatile components and the presence of trace metals are included. In addition, details of individual medicinal activities are given and the molecular structures of identified organic metabolites and their synthesis are described.</p>","PeriodicalId":77889,"journal":{"name":"Reviews on drug metabolism and drug interactions","volume":"18 1","pages":"159-90"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/dmdi.2001.18.3-4.159","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67184154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-01-01DOI: 10.1515/DMDI.2001.18.3-4.243
T. Yang, Y. Li, Q. Liu, Jun Tao, W. Wu, H. Huang,
The influence of isoflurane (Iso) on the synthesis and secretion of phosphatidylcholine (PC) of alveolar type II cells (AT II cells) injured by hydrogen peroxide (H2O2) was investigated. After primary culturing for 32 h, AT II cells isolated and purified from adult Sprague-Dawley rats were randomly divided into six groups: control group, 02.8 mM Iso group, 2.8 mM Iso group, 75 microM H2O2 group, 75 microM H2O2 + 0.28 mM Iso group, and 75 microM H202 + 2.8 mM Iso group. Synthesis and secretion of phosphatidylcholine (PC) were detected by 3H-choline chloride incorporation. It was found that 0.28 mM and 2.8 mM Iso significantly reduced PC synthesis compared with the control group (p <0.05, p <0.01, respectively), but not PC secretion. 75 microM H2O2 markedly decreased the synthesis and secretion of PC in AT II cells compared with the control group (p <0.01). 0.28 mM and 2.8 mM Iso aggravated the decrease of PC synthesis induced by H2O2 (p <0.05, p <0.01, respectively), but did not affect PC secretion. These findings suggest that Iso itself may inhibit the synthesis of PC of AT II cells in vitro and further damage the cells' function under peroxidation.
研究了异氟醚(Iso)对过氧化氢(H2O2)损伤肺泡II型细胞(AT II细胞)磷脂酰胆碱(PC)合成和分泌的影响。原代培养32 h后，取成年sd大鼠分离纯化的AT II细胞，随机分为6组:对照组、02.8 mM Iso组、2.8 mM Iso组、75 microM H2O2组、75 microM H2O2 + 0.28 mM Iso组和75 microM H202 + 2.8 mM Iso组。采用3h -氯化胆碱法检测磷脂酰胆碱(PC)的合成和分泌。结果表明，与对照组相比，0.28 mM和2.8 mM Iso显著降低了PC合成(p <0.05, p <0.01)，但对PC分泌无显著影响。与对照组相比，75 μ m H2O2显著降低了AT II细胞PC的合成和分泌(p <0.01)。0.28 mM和2.8 mM Iso加重H2O2诱导的PC合成减少(p <0.05, p <0.01)，但不影响PC分泌。这些结果表明，Iso本身可能在体外抑制AT II细胞的PC合成，进一步损害细胞在过氧化作用下的功能。
{"title":"Isoflurane Aggravates the Decrease of Phosphatidycholine Synthesis in Alveolar Type II Cells Induced by Hydrogen Peroxide","authors":"T. Yang, Y. Li, Q. Liu, Jun Tao, W. Wu, H. Huang,","doi":"10.1515/DMDI.2001.18.3-4.243","DOIUrl":"https://doi.org/10.1515/DMDI.2001.18.3-4.243","url":null,"abstract":"The influence of isoflurane (Iso) on the synthesis and secretion of phosphatidylcholine (PC) of alveolar type II cells (AT II cells) injured by hydrogen peroxide (H2O2) was investigated. After primary culturing for 32 h, AT II cells isolated and purified from adult Sprague-Dawley rats were randomly divided into six groups: control group, 02.8 mM Iso group, 2.8 mM Iso group, 75 microM H2O2 group, 75 microM H2O2 + 0.28 mM Iso group, and 75 microM H202 + 2.8 mM Iso group. Synthesis and secretion of phosphatidylcholine (PC) were detected by 3H-choline chloride incorporation. It was found that 0.28 mM and 2.8 mM Iso significantly reduced PC synthesis compared with the control group (p <0.05, p <0.01, respectively), but not PC secretion. 75 microM H2O2 markedly decreased the synthesis and secretion of PC in AT II cells compared with the control group (p <0.01). 0.28 mM and 2.8 mM Iso aggravated the decrease of PC synthesis induced by H2O2 (p <0.05, p <0.01, respectively), but did not affect PC secretion. These findings suggest that Iso itself may inhibit the synthesis of PC of AT II cells in vitro and further damage the cells' function under peroxidation.","PeriodicalId":77889,"journal":{"name":"Reviews on drug metabolism and drug interactions","volume":"18 1","pages":"243 - 250"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/DMDI.2001.18.3-4.243","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67184195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-01-01DOI: 10.1515/DMDI.2001.18.3-4.263
H. Lane, Chi-Chang Chiu, Y. Kazmi, H. Desai, Y. Lam, M. Jann, Wen‐Ho Chang
The drug-food and drug-drug interaction between grapefruit juice (GFJ) and ketoconazole (KETO) was evaluated in schizophrenic patients given a single dose of clozapine (CLZ). CLZ is metabolized primarily by CYP isozymes 3A4 and 1A2 to two principal metabolites, desmethylclozapine (DCLZ) and clozapine N-oxide (CNO). GFJ and KETO are well known potent CYP 3A4 inhibitors in the gastrointestinal tract and hepatic isozymes, respectively. Twenty-one schizophrenic patients participated in the co-administration of CLZ 50 mg and GFJ. After a one-week washout, five patients were given double the GFJ (HGFJ) dose for 7 consecutive days. In another group of five patients, ketoconazole (KETO) 400 mg was given for 7 consecutive days. At the end of the 7-day period for both groups, CLZ was coadministered with the HGFJ and KETO groups. CLZ, DCLZ and CNO were assayed by HPLC. GFJ, HGJF and ketoconazole failed to significantly change CLZ disposition. Metabolites DCLZ and CNO concentrations remained unchanged during the study. The only exception was decreased Cmax in DCLZ and CNO concentrations. These results indicate that CYP 3A4 inhibition may not be clinically significant compared to CYP 1A2, as previous studies show a dramatic increase in CLZ plasma concentrations with fluvoxamine (CYP 1A2 inhibitor). The reasons for the lack of drug-food and drug-drug interactions with CLZ and CYP 3A4 inhibitors can be explained by the higher Ki values for gastrointestinal and hepatic CYP 3A4 isozymes.
{"title":"Lack of CYP3A4 Inhibition by Grapefruit Juice and Ketoconazole upon Clozapine Administration in Vivo","authors":"H. Lane, Chi-Chang Chiu, Y. Kazmi, H. Desai, Y. Lam, M. Jann, Wen‐Ho Chang","doi":"10.1515/DMDI.2001.18.3-4.263","DOIUrl":"https://doi.org/10.1515/DMDI.2001.18.3-4.263","url":null,"abstract":"The drug-food and drug-drug interaction between grapefruit juice (GFJ) and ketoconazole (KETO) was evaluated in schizophrenic patients given a single dose of clozapine (CLZ). CLZ is metabolized primarily by CYP isozymes 3A4 and 1A2 to two principal metabolites, desmethylclozapine (DCLZ) and clozapine N-oxide (CNO). GFJ and KETO are well known potent CYP 3A4 inhibitors in the gastrointestinal tract and hepatic isozymes, respectively. Twenty-one schizophrenic patients participated in the co-administration of CLZ 50 mg and GFJ. After a one-week washout, five patients were given double the GFJ (HGFJ) dose for 7 consecutive days. In another group of five patients, ketoconazole (KETO) 400 mg was given for 7 consecutive days. At the end of the 7-day period for both groups, CLZ was coadministered with the HGFJ and KETO groups. CLZ, DCLZ and CNO were assayed by HPLC. GFJ, HGJF and ketoconazole failed to significantly change CLZ disposition. Metabolites DCLZ and CNO concentrations remained unchanged during the study. The only exception was decreased Cmax in DCLZ and CNO concentrations. These results indicate that CYP 3A4 inhibition may not be clinically significant compared to CYP 1A2, as previous studies show a dramatic increase in CLZ plasma concentrations with fluvoxamine (CYP 1A2 inhibitor). The reasons for the lack of drug-food and drug-drug interactions with CLZ and CYP 3A4 inhibitors can be explained by the higher Ki values for gastrointestinal and hepatic CYP 3A4 isozymes.","PeriodicalId":77889,"journal":{"name":"Reviews on drug metabolism and drug interactions","volume":"18 1","pages":"263 - 278"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/DMDI.2001.18.3-4.263","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67184593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2000-01-01DOI: 10.1515/DMDI.2000.16.4.299
Dehen Sür-Altiner, Banu Yenice
The effects of black tea (Camellia sinensis L.) on lipid peroxidation and glutathione (GSH) levels in carbon tetrachloride (CCl4)-treated female Wistar rats were examined. Two control groups and one treatment group were tested. The control groups were fed with a standard diet, while the black tea group was fed the standard diet plus 6% by weight dried black tea leaves. At the end of 2 months, a single dose of CCl4 (1 ml/kg, i.p.) in olive oil was administered to rats in one of the control groups and the black tea group. They were sacrificed after 2 hours. Rats in the other control group were administered olive oil in a similar fashion. Measurements were made of lipid peroxide levels in liver and plasma, glutathione levels in liver, and alanine transaminase (ALT) and aspartate transaminase (AST) activities in plasma. Liver lipid peroxide levels, plasma ALT and AST activities were significantly decreased in the black tea group compared with the CCl4-treated control group, while plasma lipid peroxide levels were not. These results are parallel to those previously found with Wistar male rats. Glutathione levels, however, were not significantly affected, in contrast to the data relating to male rats, either after CCl4 or black tea treatments. The results of our study add to the findings that black tea attenuates CCl4-induced hepatic injury but also indicates the susceptibility of glutathione levels to endocrinological effects.
{"title":"Effect of Black Tea on Lipid Peroxide and Glutathione Levels in Female Rats","authors":"Dehen Sür-Altiner, Banu Yenice","doi":"10.1515/DMDI.2000.16.4.299","DOIUrl":"https://doi.org/10.1515/DMDI.2000.16.4.299","url":null,"abstract":"The effects of black tea (Camellia sinensis L.) on lipid peroxidation and glutathione (GSH) levels in carbon tetrachloride (CCl4)-treated female Wistar rats were examined. Two control groups and one treatment group were tested. The control groups were fed with a standard diet, while the black tea group was fed the standard diet plus 6% by weight dried black tea leaves. At the end of 2 months, a single dose of CCl4 (1 ml/kg, i.p.) in olive oil was administered to rats in one of the control groups and the black tea group. They were sacrificed after 2 hours. Rats in the other control group were administered olive oil in a similar fashion. Measurements were made of lipid peroxide levels in liver and plasma, glutathione levels in liver, and alanine transaminase (ALT) and aspartate transaminase (AST) activities in plasma. Liver lipid peroxide levels, plasma ALT and AST activities were significantly decreased in the black tea group compared with the CCl4-treated control group, while plasma lipid peroxide levels were not. These results are parallel to those previously found with Wistar male rats. Glutathione levels, however, were not significantly affected, in contrast to the data relating to male rats, either after CCl4 or black tea treatments. The results of our study add to the findings that black tea attenuates CCl4-induced hepatic injury but also indicates the susceptibility of glutathione levels to endocrinological effects.","PeriodicalId":77889,"journal":{"name":"Reviews on drug metabolism and drug interactions","volume":"16 1","pages":"299 - 306"},"PeriodicalIF":0.0,"publicationDate":"2000-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/DMDI.2000.16.4.299","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67182214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2000-01-01DOI: 10.1515/DMDI.2000.17.1-4.81
L. Knowles, J. Milner
Extensive evidence points to the ability of allyl sulfides from garlic to suppress tumor proliferation both in vitro and in vivo. This antineoplastic effect is generally greater for lipid-soluble than water-soluble allyl sulfides. Both concentration and duration of exposure can increase the antiproliferative effects of lipid- and water-soluble allyl sulfides. Part of their antiproliferative effects may relate to an increase in membrane fluidity and a suppression of integrin glycoprotein IIb-IIIa mediated adhesion. Alterations in cholesterol, arachidonic acid, phospholipids and/or thiols may account for these changes in membrane function. Allyl sulfides are also recognized for their ability to suppress cellular proliferation by blocking cells in the G2/M phase and by the induction of apoptosis. This increase in the G2/M and apoptotic cell populations correlates with depressed p34cdc2 kinase activity, increased histone acetylation, increased intracellular calcium and elevated cellular peroxide production. While impressive pre-clinical data exist about the antineoplastic effects of allyl sulfur compounds, considerably more attention needs to be given to their effects in humans. The composition of the entire diet and a host of genetic/epigenetic factors will likely determine the true benefits that might arise from allyl sulfur compounds from garlic and other Allium foods.
{"title":"Allyl Sulfides Modify Cell Growth","authors":"L. Knowles, J. Milner","doi":"10.1515/DMDI.2000.17.1-4.81","DOIUrl":"https://doi.org/10.1515/DMDI.2000.17.1-4.81","url":null,"abstract":"Extensive evidence points to the ability of allyl sulfides from garlic to suppress tumor proliferation both in vitro and in vivo. This antineoplastic effect is generally greater for lipid-soluble than water-soluble allyl sulfides. Both concentration and duration of exposure can increase the antiproliferative effects of lipid- and water-soluble allyl sulfides. Part of their antiproliferative effects may relate to an increase in membrane fluidity and a suppression of integrin glycoprotein IIb-IIIa mediated adhesion. Alterations in cholesterol, arachidonic acid, phospholipids and/or thiols may account for these changes in membrane function. Allyl sulfides are also recognized for their ability to suppress cellular proliferation by blocking cells in the G2/M phase and by the induction of apoptosis. This increase in the G2/M and apoptotic cell populations correlates with depressed p34cdc2 kinase activity, increased histone acetylation, increased intracellular calcium and elevated cellular peroxide production. While impressive pre-clinical data exist about the antineoplastic effects of allyl sulfur compounds, considerably more attention needs to be given to their effects in humans. The composition of the entire diet and a host of genetic/epigenetic factors will likely determine the true benefits that might arise from allyl sulfur compounds from garlic and other Allium foods.","PeriodicalId":77889,"journal":{"name":"Reviews on drug metabolism and drug interactions","volume":"17 1","pages":"108 - 81"},"PeriodicalIF":0.0,"publicationDate":"2000-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/DMDI.2000.17.1-4.81","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67183259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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