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M.a. Bazeed - One of the best experts on this subject based on the ideXlab platform.
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Changes in the expression of cytochrome P450 2E1 and the activity of carcinogen-metabolizing enzymes in Schistosoma haematobium-infected human bladder tissues.
Toxicology, 2001Co-Authors: Salah A. Sheweita, M.r. Abu El-maati, F.g. El-shahat, M.a. BazeedAbstract:Abstract The bioactivation of N -nitrosamines and polycyclic aromatic hydrocarbons (PAHs) is mediated primarily by the mixed-function oxidase system, which includes dimethylnitrosamine N- demethylase I, arylhydrocarbon [benzo( a )pyerne] hydroxylase, cytochrome P 450, cytochrome b 5 , and ethoxycoumarin deethylase. Most of carcinogens and xenobiotics are conjugated and detoxified by phase II drug-metabolizing enzymes such as glutathione S -transferase. The present study showed the influence of Schistosoma haematobium on the activity of the above-mentioned enzymes in 13 schistosome-infected human bladder tissues compared with those of 15 schistosome-free samples. The contents of cytochrome P 450 and cytochrome b 5 were increased in the bladder tissues by 48 and 69%, respectively. Moreover, the activities of dimethylnitrosamine N- demethylase I and arylhydrocarbon hydroxylase, ethoxycoumarin O -deethylase, ethoxyresourfin O -deethylase, and Pentoxyresorufin O -Pentoxyresorufin were increased by 75, 159, 49, 63 and 44%, respectively. The signal intensity for cytochrome P 450 2E1 was greatly increased over the control. Also, the activity of glutathione S -transferase was increased by 89%. On the other hand, the activity of glutathione reductase and the level of reduced glutathione were decreased by 40 and 57%, respectively. Interestingly, the level of free radical, thiobarbituric acid reactive substance, was increased in the schistosome-infected human bladder tissues by 125%. The present study clearly demonstrated that S. haematobium changes the activity of carcinogen-metabolizing enzymes. We conclude that S. haematobium could enhance the carcinogenicity of polycyclic aromatic hydrocarbons (e.g. benzo(a)pyrene) and N- nitrosamines (e.g. dimethylnitrosamine) through induction of their corresponding bioactivating enzymes in human bladder tissues.
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Changes in the expression of cytochrome P450 2E1 and the activity of carcinogen-metabolizing enzymes in Schistosoma haematobium-infected human bladder tissues.
Toxicology, 2001Co-Authors: Salah A. Sheweita, F.g. El-shahat, M.r. Abu El-maati, M.a. BazeedAbstract:Abstract The bioactivation of N -nitrosamines and polycyclic aromatic hydrocarbons (PAHs) is mediated primarily by the mixed-function oxidase system, which includes dimethylnitrosamine N- demethylase I, arylhydrocarbon [benzo( a )pyerne] hydroxylase, cytochrome P 450, cytochrome b 5 , and ethoxycoumarin deethylase. Most of carcinogens and xenobiotics are conjugated and detoxified by phase II drug-metabolizing enzymes such as glutathione S -transferase. The present study showed the influence of Schistosoma haematobium on the activity of the above-mentioned enzymes in 13 schistosome-infected human bladder tissues compared with those of 15 schistosome-free samples. The contents of cytochrome P 450 and cytochrome b 5 were increased in the bladder tissues by 48 and 69%, respectively. Moreover, the activities of dimethylnitrosamine N- demethylase I and arylhydrocarbon hydroxylase, ethoxycoumarin O -deethylase, ethoxyresourfin O -deethylase, and Pentoxyresorufin O -Pentoxyresorufin were increased by 75, 159, 49, 63 and 44%, respectively. The signal intensity for cytochrome P 450 2E1 was greatly increased over the control. Also, the activity of glutathione S -transferase was increased by 89%. On the other hand, the activity of glutathione reductase and the level of reduced glutathione were decreased by 40 and 57%, respectively. Interestingly, the level of free radical, thiobarbituric acid reactive substance, was increased in the schistosome-infected human bladder tissues by 125%. The present study clearly demonstrated that S. haematobium changes the activity of carcinogen-metabolizing enzymes. We conclude that S. haematobium could enhance the carcinogenicity of polycyclic aromatic hydrocarbons (e.g. benzo(a)pyrene) and N- nitrosamines (e.g. dimethylnitrosamine) through induction of their corresponding bioactivating enzymes in human bladder tissues.
Salah A. Sheweita - One of the best experts on this subject based on the ideXlab platform.
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Changes in the expression of cytochrome P450 2E1 and the activity of carcinogen-metabolizing enzymes in Schistosoma haematobium-infected human bladder tissues.
Toxicology, 2001Co-Authors: Salah A. Sheweita, M.r. Abu El-maati, F.g. El-shahat, M.a. BazeedAbstract:Abstract The bioactivation of N -nitrosamines and polycyclic aromatic hydrocarbons (PAHs) is mediated primarily by the mixed-function oxidase system, which includes dimethylnitrosamine N- demethylase I, arylhydrocarbon [benzo( a )pyerne] hydroxylase, cytochrome P 450, cytochrome b 5 , and ethoxycoumarin deethylase. Most of carcinogens and xenobiotics are conjugated and detoxified by phase II drug-metabolizing enzymes such as glutathione S -transferase. The present study showed the influence of Schistosoma haematobium on the activity of the above-mentioned enzymes in 13 schistosome-infected human bladder tissues compared with those of 15 schistosome-free samples. The contents of cytochrome P 450 and cytochrome b 5 were increased in the bladder tissues by 48 and 69%, respectively. Moreover, the activities of dimethylnitrosamine N- demethylase I and arylhydrocarbon hydroxylase, ethoxycoumarin O -deethylase, ethoxyresourfin O -deethylase, and Pentoxyresorufin O -Pentoxyresorufin were increased by 75, 159, 49, 63 and 44%, respectively. The signal intensity for cytochrome P 450 2E1 was greatly increased over the control. Also, the activity of glutathione S -transferase was increased by 89%. On the other hand, the activity of glutathione reductase and the level of reduced glutathione were decreased by 40 and 57%, respectively. Interestingly, the level of free radical, thiobarbituric acid reactive substance, was increased in the schistosome-infected human bladder tissues by 125%. The present study clearly demonstrated that S. haematobium changes the activity of carcinogen-metabolizing enzymes. We conclude that S. haematobium could enhance the carcinogenicity of polycyclic aromatic hydrocarbons (e.g. benzo(a)pyrene) and N- nitrosamines (e.g. dimethylnitrosamine) through induction of their corresponding bioactivating enzymes in human bladder tissues.
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Changes in the expression of cytochrome P450 2E1 and the activity of carcinogen-metabolizing enzymes in Schistosoma haematobium-infected human bladder tissues.
Toxicology, 2001Co-Authors: Salah A. Sheweita, F.g. El-shahat, M.r. Abu El-maati, M.a. BazeedAbstract:Abstract The bioactivation of N -nitrosamines and polycyclic aromatic hydrocarbons (PAHs) is mediated primarily by the mixed-function oxidase system, which includes dimethylnitrosamine N- demethylase I, arylhydrocarbon [benzo( a )pyerne] hydroxylase, cytochrome P 450, cytochrome b 5 , and ethoxycoumarin deethylase. Most of carcinogens and xenobiotics are conjugated and detoxified by phase II drug-metabolizing enzymes such as glutathione S -transferase. The present study showed the influence of Schistosoma haematobium on the activity of the above-mentioned enzymes in 13 schistosome-infected human bladder tissues compared with those of 15 schistosome-free samples. The contents of cytochrome P 450 and cytochrome b 5 were increased in the bladder tissues by 48 and 69%, respectively. Moreover, the activities of dimethylnitrosamine N- demethylase I and arylhydrocarbon hydroxylase, ethoxycoumarin O -deethylase, ethoxyresourfin O -deethylase, and Pentoxyresorufin O -Pentoxyresorufin were increased by 75, 159, 49, 63 and 44%, respectively. The signal intensity for cytochrome P 450 2E1 was greatly increased over the control. Also, the activity of glutathione S -transferase was increased by 89%. On the other hand, the activity of glutathione reductase and the level of reduced glutathione were decreased by 40 and 57%, respectively. Interestingly, the level of free radical, thiobarbituric acid reactive substance, was increased in the schistosome-infected human bladder tissues by 125%. The present study clearly demonstrated that S. haematobium changes the activity of carcinogen-metabolizing enzymes. We conclude that S. haematobium could enhance the carcinogenicity of polycyclic aromatic hydrocarbons (e.g. benzo(a)pyrene) and N- nitrosamines (e.g. dimethylnitrosamine) through induction of their corresponding bioactivating enzymes in human bladder tissues.
F.g. El-shahat - One of the best experts on this subject based on the ideXlab platform.
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Changes in the expression of cytochrome P450 2E1 and the activity of carcinogen-metabolizing enzymes in Schistosoma haematobium-infected human bladder tissues.
Toxicology, 2001Co-Authors: Salah A. Sheweita, M.r. Abu El-maati, F.g. El-shahat, M.a. BazeedAbstract:Abstract The bioactivation of N -nitrosamines and polycyclic aromatic hydrocarbons (PAHs) is mediated primarily by the mixed-function oxidase system, which includes dimethylnitrosamine N- demethylase I, arylhydrocarbon [benzo( a )pyerne] hydroxylase, cytochrome P 450, cytochrome b 5 , and ethoxycoumarin deethylase. Most of carcinogens and xenobiotics are conjugated and detoxified by phase II drug-metabolizing enzymes such as glutathione S -transferase. The present study showed the influence of Schistosoma haematobium on the activity of the above-mentioned enzymes in 13 schistosome-infected human bladder tissues compared with those of 15 schistosome-free samples. The contents of cytochrome P 450 and cytochrome b 5 were increased in the bladder tissues by 48 and 69%, respectively. Moreover, the activities of dimethylnitrosamine N- demethylase I and arylhydrocarbon hydroxylase, ethoxycoumarin O -deethylase, ethoxyresourfin O -deethylase, and Pentoxyresorufin O -Pentoxyresorufin were increased by 75, 159, 49, 63 and 44%, respectively. The signal intensity for cytochrome P 450 2E1 was greatly increased over the control. Also, the activity of glutathione S -transferase was increased by 89%. On the other hand, the activity of glutathione reductase and the level of reduced glutathione were decreased by 40 and 57%, respectively. Interestingly, the level of free radical, thiobarbituric acid reactive substance, was increased in the schistosome-infected human bladder tissues by 125%. The present study clearly demonstrated that S. haematobium changes the activity of carcinogen-metabolizing enzymes. We conclude that S. haematobium could enhance the carcinogenicity of polycyclic aromatic hydrocarbons (e.g. benzo(a)pyrene) and N- nitrosamines (e.g. dimethylnitrosamine) through induction of their corresponding bioactivating enzymes in human bladder tissues.
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Changes in the expression of cytochrome P450 2E1 and the activity of carcinogen-metabolizing enzymes in Schistosoma haematobium-infected human bladder tissues.
Toxicology, 2001Co-Authors: Salah A. Sheweita, F.g. El-shahat, M.r. Abu El-maati, M.a. BazeedAbstract:Abstract The bioactivation of N -nitrosamines and polycyclic aromatic hydrocarbons (PAHs) is mediated primarily by the mixed-function oxidase system, which includes dimethylnitrosamine N- demethylase I, arylhydrocarbon [benzo( a )pyerne] hydroxylase, cytochrome P 450, cytochrome b 5 , and ethoxycoumarin deethylase. Most of carcinogens and xenobiotics are conjugated and detoxified by phase II drug-metabolizing enzymes such as glutathione S -transferase. The present study showed the influence of Schistosoma haematobium on the activity of the above-mentioned enzymes in 13 schistosome-infected human bladder tissues compared with those of 15 schistosome-free samples. The contents of cytochrome P 450 and cytochrome b 5 were increased in the bladder tissues by 48 and 69%, respectively. Moreover, the activities of dimethylnitrosamine N- demethylase I and arylhydrocarbon hydroxylase, ethoxycoumarin O -deethylase, ethoxyresourfin O -deethylase, and Pentoxyresorufin O -Pentoxyresorufin were increased by 75, 159, 49, 63 and 44%, respectively. The signal intensity for cytochrome P 450 2E1 was greatly increased over the control. Also, the activity of glutathione S -transferase was increased by 89%. On the other hand, the activity of glutathione reductase and the level of reduced glutathione were decreased by 40 and 57%, respectively. Interestingly, the level of free radical, thiobarbituric acid reactive substance, was increased in the schistosome-infected human bladder tissues by 125%. The present study clearly demonstrated that S. haematobium changes the activity of carcinogen-metabolizing enzymes. We conclude that S. haematobium could enhance the carcinogenicity of polycyclic aromatic hydrocarbons (e.g. benzo(a)pyrene) and N- nitrosamines (e.g. dimethylnitrosamine) through induction of their corresponding bioactivating enzymes in human bladder tissues.
R.p. Remmel - One of the best experts on this subject based on the ideXlab platform.
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probing enhanced cytochrome p450 2b1 2 activity in rat hepatocyte spheroids through confocal laser scanning microscopy
Cell Transplantation, 2001Co-Authors: E.s. Tzanakakis, Changchun Hsiao, Taku Matsushita, R.p. RemmelAbstract:Cytochrome P450 (CYP450) enzymes are essential for xenobiotic metabolism. Although CYP450s are found in many tissues, CYP2B1/2 are primarily expressed in the rat liver. The constitutive expression in vivo of CYP2B1/2 is low but it is induced in the presence of various drugs such as phenobarbital (PB). In this study, CYP2B1/2 activity in cultured hepatocytes was assessed in situ with the introduction of a fluorogenic substrate, Pentoxyresorufin. The product of 7-Pentoxyresorufin-O-dealkylation (PROD), which is catalyzed specifically by CYP2B1/2, was detected using confocal laser scanning microscopy (CLSM). Primary hepatocytes cultured as monolayers on collagen-coated surfaces exhibited background PROD activity and minimal PB inducibility after 4 days in culture. In contrast, rat hepatocytes organized in compacted aggregates, or spheroids, exhibited higher levels of PROD activity and retained their ability for PB induction. The results from the CLSM analysis were verified by RT-PCR and Western immunoblotting analysis. Furthermore, CLSM in conjunction with image processing techniques and three-dimensional reconstruction revealed the localization of enhanced PROD activity in the center of spheroids. The results support the use of CLSM as a powerful tool for investigating CYP2B1/2 activity in cultured rat hepatocytes.
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Probing enhanced cytochrome P450 2B1/2 activity in rat hepatocyte spheroids through confocal laser scanning microscopy.
Cell transplantation, 2001Co-Authors: E.s. Tzanakakis, Changchun Hsiao, Taku Matsushita, R.p. RemmelAbstract:Cytochrome P450 (CYP450) enzymes are essential for xenobiotic metabolism. Although CYP450s are found in many tissues, CYP2B1/2 are primarily expressed in the rat liver. The constitutive expression in vivo of CYP2B1/2 is low but it is induced in the presence of various drugs such as phenobarbital (PB). In this study, CYP2B1/2 activity in cultured hepatocytes was assessed in situ with the introduction of a fluorogenic substrate, Pentoxyresorufin. The product of 7-Pentoxyresorufin-O-dealkylation (PROD), which is catalyzed specifically by CYP2B1/2, was detected using confocal laser scanning microscopy (CLSM). Primary hepatocytes cultured as monolayers on collagen-coated surfaces exhibited background PROD activity and minimal PB inducibility after 4 days in culture. In contrast, rat hepatocytes organized in compacted aggregates, or spheroids, exhibited higher levels of PROD activity and retained their ability for PB induction. The results from the CLSM analysis were verified by RT-PCR and Western immunoblotting analysis. Furthermore, CLSM in conjunction with image processing techniques and three-dimensional reconstruction revealed the localization of enhanced PROD activity in the center of spheroids. The results support the use of CLSM as a powerful tool for investigating CYP2B1/2 activity in cultured rat hepatocytes.
Tzuu-huei Ueng - One of the best experts on this subject based on the ideXlab platform.
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Induction of rat hepatic cytochrome P-450 by ketamine and its toxicological implications.
Journal of Toxicology and Environmental Health, 2005Co-Authors: Wei-hung Chan, Wei-zen Sun, Tzuu-huei UengAbstract:Ketamine is a common intravenous anesthetic and a frequent drug of abuse, alone or in combination with cocaine. However, the pharmacokinetic effects of ketamine have not been fully investigated. This study determined the effects of ketamine on cytochrome P-450 (P-450)-dependent catalytic activities, protein levels, and hepatotoxicity using male Wistar rats treated with 10, 20, 40, or 80 mg/kg ketamine intraperitoneally twice daily for 4 d. Treatment with ketamine produced a dose-dependent increase of Pentoxyresorufin O-dealkylation activity of liver microsomes. Treatment with 80 mg/kg ketamine resulted in 14-, 3-, and 2-fold rise in O-dealkylation of Pentoxyresorufin, ethoxyresorufin, and methoxyresorufin of rat liver microsomes, respectively. The treatment produced 31% and 86% increases in 7-ethoxycoumarin O-deethylation and erythromycin N-demethylation, respectively. In addition, aniline hydroxylation activity was elevated by 62%. Protein blot analysis of liver microsomal proteins revealed that 80 mg/kg...
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Induction of rat hepatic cytochrome P-450 by ketamine and its toxicological implications.
Journal of toxicology and environmental health. Part A, 2005Co-Authors: Wei-hung Chan, Wei-zen Sun, Tzuu-huei UengAbstract:Ketamine is a common intravenous anesthetic and a frequent drug of abuse, alone or in combination with cocaine. However, the pharmacokinetic effects of ketamine have not been fully investigated. This study determined the effects of ketamine on cytochrome P-450 (P-450)-dependent catalytic activities, protein levels, and hepatotoxicity using male Wistar rats treated with 10, 20, 40, or 80 mg/kg ketamine intraperitoneally twice daily for 4 d. Treatment with ketamine produced a dose-dependent increase of Pentoxyresorufin O-dealkylation activity of liver microsomes. Treatment with 80 mg/kg ketamine resulted in 14-, 3-, and 2-fold rise in O-dealkylation of Pentoxyresorufin, ethoxyresorufin, and methoxyresorufin of rat liver microsomes, respectively. The treatment produced 31% and 86% increases in 7-ethoxycoumarin O-deethylation and erythromycin N-demethylation, respectively. In addition, aniline hydroxylation activity was elevated by 62%. Protein blot analysis of liver microsomal proteins revealed that 80 mg/kg ketamine induced P-450 1A, 2B, 2E1, and 3A proteins by 2-, 13-, 2-, and 2-fold, respectively. In reversibility study, ketamine-induced Pentoxyresorufin O-dealkylation, 7-ethoxycoumarin O-deethylation, erythromycin N-demethylation, and methoxyresorufin O-demethylation activities of liver microsomes prepared from rats 4 d after ketamine treatment were 75%, 48%, 29%, and 38% lower than the respective activities of liver microsomes prepared from rats 1 d after treatment. Protein blot analysis showed that ketamine-induced P-450 2B1/2 proteins also decreased in a time-dependent manner in 4 d. In hepatotoxicity study, treatment of rats with 1 ml/kg CCl4 produced a 7-fold increase in serum alanine aminotransferase activity level and a 17-fold rise in rats pretreated with 80 mg/kg ketamine for 4 d. Treatment of ICR mice with 120 mg/kg cocaine produced a 17% mortality, whereas the same dose of cocaine produced a 50% mortality in mice pretreated with ketamine. Treatment of mice with 100 mg/kg cocaine produced a 76-fold increase in serum alanine aminotransferase activity level and a 260-fold rise in mice pretreated with 80 mg/kg ketamine for 4 d. The present study shows that ketamine induces the expression of multiple forms of P-450 in rat liver microsomes and increases CCl4-induced liver toxicity and cocaine-mediated acute toxicity. Other potential pharmacological or toxicological events related to ketamine use need to be further explored.
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Modulation of microsomal cytochrome P450 by Scutellariae Radix and Gentianae scabrae Radix in rat liver.
The American journal of Chinese medicine, 1996Co-Authors: Jaw Jou Kang, Yi Chien Chen, Wei Chung Kuo, Terri Chen, Yu Wen Cheng, Min-liang Kuo, Tzuu-huei UengAbstract:The present study has determined the effects of Scutellariae Radix (Huangqin) and Gentianae scabrae Radix (Longdan) on liver microsomal cytochrome P450 (P450)-dependent mono-oxygenases using rats pretreated with crude extracts of medicinal herbs. Scutellariae Radix resulted in a 53% decrease of Pentoxyresorufin O-dealkylase activity in liver microsomes. In contrast, Gentianae scabrae Radix caused a 50% increase of benzo(a)pyrene hydroxylase activity. Immunoblotting analysis of liver microsomes revealed that Scutellariae Radix induced and suppressed the levels of P450 1A and 2B proteins, respectively. Scutellariae and Gentianae scabrae Radixes had no effects on microsomal aniline hydroxylase activity and P450 2E1 protein.