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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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Formato: | Texto |
Lenguaje: | English |
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Nature Publishing Group
2002
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2375263/ https://www.ncbi.nlm.nih.gov/pubmed/11870548 http://dx.doi.org/10.1038/sj.bjc.6600102 |
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author | Caballero, F Gerez, E Batlle, A Vazquez, E |
author_facet | Caballero, F Gerez, E Batlle, A Vazquez, E |
author_sort | Caballero, F |
collection | PubMed |
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 CF1 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. British Journal of Cancer (2002) 86, 630–635. DOI: 10.1038/sj/bjc/6600102 www.bjcancer.com © 2002 Cancer Research UK |
format | Text |
id | pubmed-2375263 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2002 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-23752632009-09-10 Interaction of cimetidine with P450 in a mouse model of hepatocarcinogenesis initiation Caballero, F Gerez, E Batlle, A Vazquez, E Br J Cancer Experimental Therapeutics 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 CF1 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. British Journal of Cancer (2002) 86, 630–635. DOI: 10.1038/sj/bjc/6600102 www.bjcancer.com © 2002 Cancer Research UK Nature Publishing Group 2002-02-12 /pmc/articles/PMC2375263/ /pubmed/11870548 http://dx.doi.org/10.1038/sj.bjc.6600102 Text en Copyright © 2002 Cancer Research UK https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Experimental Therapeutics Caballero, F Gerez, E Batlle, A Vazquez, E Interaction of cimetidine with P450 in a mouse model of hepatocarcinogenesis initiation |
title | 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_short | 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 |
topic | Experimental Therapeutics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2375263/ https://www.ncbi.nlm.nih.gov/pubmed/11870548 http://dx.doi.org/10.1038/sj.bjc.6600102 |
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