Interaction of cimetidine with P450 in a mouse model of hepatocarcinogenesis initiation
Many drugs and xenobiotics are lipophilic and they should be transformed into more polar water soluble compounds to be excreted. Cimetidine inhibits cytochrome P450. The aim of this study was to investigate the preventive and/or reversal action of cimetidine on cytochrome P450 induction and other me...
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todo:paper_00070920_v86_n4_p630_Caballero2023-10-03T14:05:26Z Interaction of cimetidine with P450 in a mouse model of hepatocarcinogenesis initiation Caballero, F. Gerez, E. Batlle, A. Vazquez, E. Cimetidine Cytochrome P450 Haem metabolism Hepatocarcinogenesis Oxidative stress P-dimethylaminoazobenzene 4 dimethylaminoazobenzene 5 aminolevulinate synthase catalase cimetidine cytochrome P450 glutathione transferase heme heme oxygenase malonaldehyde thiobarbituric acid reactive substance xenobiotic agent animal experiment animal model animal tissue article controlled study enzyme induction enzyme inhibition lipid peroxidation liver cancer liver carcinogenesis liver injury male mouse nonhuman oxidative stress priority journal 5-Aminolevulinate Synthetase Animals Body Weight Carcinogens Catalase Cimetidine Cytochrome P-450 Enzyme System Enzyme Inhibitors Glutathione Transferase Heme Liver Neoplasms, Experimental Male Mice p-Dimethylaminoazobenzene Thiobarbituric Acid Reactive Substances Many drugs and xenobiotics are lipophilic and they should be transformed into more polar water soluble compounds to be excreted. Cimetidine inhibits cytochrome P450. The aim of this study was to investigate the preventive and/or reversal action of cimetidine on cytochrome P450 induction and other metabolic alterations provoked by the carcinogen p-dimethylaminoazobenzene. A group of male CFI mice received a standard laboratory diet and another group was placed on dietary p-dimethylaminoazobenzene (0.5% w w-1). After 40 days of treatment, animals of both groups received p-dimethylaminoazobenzene and two weekly doses of cimetidine (120 mg kg-1, i.p.) during a following period of 35 days. Cimetidine prevented and reversed δ-aminolevulinate synthetase induction and cytochrome P450 enhancement provoked by p-dimethylaminoazobenzene. However, cimetidine did not restore haem oxygenase activity decreased by p-dimethylaminoazobenzene. Enhancement in glutathione S-transferase activity provoked by p-dimethylaminoazobenzene, persisted in those animals then treated with cimetidine. This drug did not modify either increased lipid peroxidation or diminution of the natural antioxidant defence system (inferred by catalase activity) induced by p-dimethylaminoazobenzene. In conclusion, although cimetidine treatment partially prevented and reversed cytochrome P450 induction, and alteration on haem metabolism provoked by p-dimethylaminoazobenzene AB, it did not reverse liver damage or lipid peroxidation. These results further support our hypothesis on the necessary existence of a multiple biochemical pathway disturbance for the onset of hepatocarcinogenesis initiation. © 2002 Cancer Research UK. Fil:Gerez, E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Batlle, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Vazquez, E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00070920_v86_n4_p630_Caballero |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Cimetidine Cytochrome P450 Haem metabolism Hepatocarcinogenesis Oxidative stress P-dimethylaminoazobenzene 4 dimethylaminoazobenzene 5 aminolevulinate synthase catalase cimetidine cytochrome P450 glutathione transferase heme heme oxygenase malonaldehyde thiobarbituric acid reactive substance xenobiotic agent animal experiment animal model animal tissue article controlled study enzyme induction enzyme inhibition lipid peroxidation liver cancer liver carcinogenesis liver injury male mouse nonhuman oxidative stress priority journal 5-Aminolevulinate Synthetase Animals Body Weight Carcinogens Catalase Cimetidine Cytochrome P-450 Enzyme System Enzyme Inhibitors Glutathione Transferase Heme Liver Neoplasms, Experimental Male Mice p-Dimethylaminoazobenzene Thiobarbituric Acid Reactive Substances |
| spellingShingle |
Cimetidine Cytochrome P450 Haem metabolism Hepatocarcinogenesis Oxidative stress P-dimethylaminoazobenzene 4 dimethylaminoazobenzene 5 aminolevulinate synthase catalase cimetidine cytochrome P450 glutathione transferase heme heme oxygenase malonaldehyde thiobarbituric acid reactive substance xenobiotic agent animal experiment animal model animal tissue article controlled study enzyme induction enzyme inhibition lipid peroxidation liver cancer liver carcinogenesis liver injury male mouse nonhuman oxidative stress priority journal 5-Aminolevulinate Synthetase Animals Body Weight Carcinogens Catalase Cimetidine Cytochrome P-450 Enzyme System Enzyme Inhibitors Glutathione Transferase Heme Liver Neoplasms, Experimental Male Mice p-Dimethylaminoazobenzene Thiobarbituric Acid Reactive Substances Caballero, F. Gerez, E. Batlle, A. Vazquez, E. Interaction of cimetidine with P450 in a mouse model of hepatocarcinogenesis initiation |
| topic_facet |
Cimetidine Cytochrome P450 Haem metabolism Hepatocarcinogenesis Oxidative stress P-dimethylaminoazobenzene 4 dimethylaminoazobenzene 5 aminolevulinate synthase catalase cimetidine cytochrome P450 glutathione transferase heme heme oxygenase malonaldehyde thiobarbituric acid reactive substance xenobiotic agent animal experiment animal model animal tissue article controlled study enzyme induction enzyme inhibition lipid peroxidation liver cancer liver carcinogenesis liver injury male mouse nonhuman oxidative stress priority journal 5-Aminolevulinate Synthetase Animals Body Weight Carcinogens Catalase Cimetidine Cytochrome P-450 Enzyme System Enzyme Inhibitors Glutathione Transferase Heme Liver Neoplasms, Experimental Male Mice p-Dimethylaminoazobenzene Thiobarbituric Acid Reactive Substances |
| description |
Many drugs and xenobiotics are lipophilic and they should be transformed into more polar water soluble compounds to be excreted. Cimetidine inhibits cytochrome P450. The aim of this study was to investigate the preventive and/or reversal action of cimetidine on cytochrome P450 induction and other metabolic alterations provoked by the carcinogen p-dimethylaminoazobenzene. A group of male CFI mice received a standard laboratory diet and another group was placed on dietary p-dimethylaminoazobenzene (0.5% w w-1). After 40 days of treatment, animals of both groups received p-dimethylaminoazobenzene and two weekly doses of cimetidine (120 mg kg-1, i.p.) during a following period of 35 days. Cimetidine prevented and reversed δ-aminolevulinate synthetase induction and cytochrome P450 enhancement provoked by p-dimethylaminoazobenzene. However, cimetidine did not restore haem oxygenase activity decreased by p-dimethylaminoazobenzene. Enhancement in glutathione S-transferase activity provoked by p-dimethylaminoazobenzene, persisted in those animals then treated with cimetidine. This drug did not modify either increased lipid peroxidation or diminution of the natural antioxidant defence system (inferred by catalase activity) induced by p-dimethylaminoazobenzene. In conclusion, although cimetidine treatment partially prevented and reversed cytochrome P450 induction, and alteration on haem metabolism provoked by p-dimethylaminoazobenzene AB, it did not reverse liver damage or lipid peroxidation. These results further support our hypothesis on the necessary existence of a multiple biochemical pathway disturbance for the onset of hepatocarcinogenesis initiation. © 2002 Cancer Research UK. |
| format |
JOUR |
| author |
Caballero, F. Gerez, E. Batlle, A. Vazquez, E. |
| author_facet |
Caballero, F. Gerez, E. Batlle, A. Vazquez, E. |
| author_sort |
Caballero, F. |
| title |
Interaction of cimetidine with P450 in a mouse model of hepatocarcinogenesis initiation |
| title_short |
Interaction of cimetidine with P450 in a mouse model of hepatocarcinogenesis initiation |
| title_full |
Interaction of cimetidine with P450 in a mouse model of hepatocarcinogenesis initiation |
| title_fullStr |
Interaction of cimetidine with P450 in a mouse model of hepatocarcinogenesis initiation |
| title_full_unstemmed |
Interaction of cimetidine with P450 in a mouse model of hepatocarcinogenesis initiation |
| title_sort |
interaction of cimetidine with p450 in a mouse model of hepatocarcinogenesis initiation |
| url |
http://hdl.handle.net/20.500.12110/paper_00070920_v86_n4_p630_Caballero |
| work_keys_str_mv |
AT caballerof interactionofcimetidinewithp450inamousemodelofhepatocarcinogenesisinitiation AT gereze interactionofcimetidinewithp450inamousemodelofhepatocarcinogenesisinitiation AT batllea interactionofcimetidinewithp450inamousemodelofhepatocarcinogenesisinitiation AT vazqueze interactionofcimetidinewithp450inamousemodelofhepatocarcinogenesisinitiation |
| _version_ |
1807315854927331328 |