Cargando…

Erectile Dysfunction Drugs Changed the Protein Expressions and Activities of Drug-Metabolising Enzymes in the Liver of Male Rats

Erectile dysfunction (ED) is a major health problem and is mainly associated with the persistent inability of men to maintain sufficient erection for satisfactory sexual performance. Millions of men are using sildenafil, vardenafil, and/or tadalafil for ED treatment. Cytochrome P450s (CYPs) play a c...

Descripción completa

Detalles Bibliográficos
Autores principales: Sheweita, Salah A., Wally, Mona, Hassan, Mostafa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5075309/
https://www.ncbi.nlm.nih.gov/pubmed/27800121
http://dx.doi.org/10.1155/2016/4970906
_version_ 1782461833716695040
author Sheweita, Salah A.
Wally, Mona
Hassan, Mostafa
author_facet Sheweita, Salah A.
Wally, Mona
Hassan, Mostafa
author_sort Sheweita, Salah A.
collection PubMed
description Erectile dysfunction (ED) is a major health problem and is mainly associated with the persistent inability of men to maintain sufficient erection for satisfactory sexual performance. Millions of men are using sildenafil, vardenafil, and/or tadalafil for ED treatment. Cytochrome P450s (CYPs) play a central role in the metabolism of a wide range of xenobiotics as well as endogenous compounds. Susceptibility of individuals to the adverse effects of different drugs is mainly dependent on the expression of CYPs proteins. Therefore, changes in activities of phase I drug-metabolising enzymes [arylhydrocarbon hydroxylase (AHH), dimethylnitrosamine N-demethylase (DMN-dI), 7-ethoxycoumarin-O-deethylase (ECOD), and ethoxyresorufin-O-deethylase ((EROD)] and the protein expression of different CYPs isozymes (CYP1A2, CYP2E1, CYP2B1/2, CYP3A4, CYP2C23, and CYP2C6) were determined after treatment of male rats with either low or high doses of sildenafil (Viagra), tadalafil (Cialis), and/or vardenafil (Levitra) for 3 weeks. The present study showed that low doses of tadalafil and vardenafil increased DMN-dI activity by 32 and 23%, respectively. On the other hand, high doses of tadalafil, vardenafil, and sildenafil decreased such activity by 50, 56, and 52%, respectively. In addition, low doses of tadalafil and vardenafil induced the protein expression of CYP2E1. On the other hand, high doses of either tadalafil or sildenafil were more potent inhibitors to CYP2E1 expression than vardenafil. Moreover, low doses of both vardenafil and sildenafil markedly increased AHH activity by 162 and 247%, respectively, whereas high doses of tadalafil, vardenafil, and sildenafil inhibited such activity by 36, 49, and 57% and inhibited the EROD activity by 39, 49, and 33%, respectively. Low and high doses of tadalafil, vardenafil, and sildenafil inhibited the activity of NADPH-cytochrome c reductase as well as its protein expression. In addition, such drugs inhibited the expression of CYP B1/2 along with its corresponding enzyme marker ECOD activity. It is concluded that changes in the expression and activity of phase I drug-metabolising enzymes could change the normal metabolic pathways and might enhance the deleterious effects of exogenous as well as endogenous compounds.
format Online
Article
Text
id pubmed-5075309
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Hindawi Publishing Corporation
record_format MEDLINE/PubMed
spelling pubmed-50753092016-10-31 Erectile Dysfunction Drugs Changed the Protein Expressions and Activities of Drug-Metabolising Enzymes in the Liver of Male Rats Sheweita, Salah A. Wally, Mona Hassan, Mostafa Oxid Med Cell Longev Research Article Erectile dysfunction (ED) is a major health problem and is mainly associated with the persistent inability of men to maintain sufficient erection for satisfactory sexual performance. Millions of men are using sildenafil, vardenafil, and/or tadalafil for ED treatment. Cytochrome P450s (CYPs) play a central role in the metabolism of a wide range of xenobiotics as well as endogenous compounds. Susceptibility of individuals to the adverse effects of different drugs is mainly dependent on the expression of CYPs proteins. Therefore, changes in activities of phase I drug-metabolising enzymes [arylhydrocarbon hydroxylase (AHH), dimethylnitrosamine N-demethylase (DMN-dI), 7-ethoxycoumarin-O-deethylase (ECOD), and ethoxyresorufin-O-deethylase ((EROD)] and the protein expression of different CYPs isozymes (CYP1A2, CYP2E1, CYP2B1/2, CYP3A4, CYP2C23, and CYP2C6) were determined after treatment of male rats with either low or high doses of sildenafil (Viagra), tadalafil (Cialis), and/or vardenafil (Levitra) for 3 weeks. The present study showed that low doses of tadalafil and vardenafil increased DMN-dI activity by 32 and 23%, respectively. On the other hand, high doses of tadalafil, vardenafil, and sildenafil decreased such activity by 50, 56, and 52%, respectively. In addition, low doses of tadalafil and vardenafil induced the protein expression of CYP2E1. On the other hand, high doses of either tadalafil or sildenafil were more potent inhibitors to CYP2E1 expression than vardenafil. Moreover, low doses of both vardenafil and sildenafil markedly increased AHH activity by 162 and 247%, respectively, whereas high doses of tadalafil, vardenafil, and sildenafil inhibited such activity by 36, 49, and 57% and inhibited the EROD activity by 39, 49, and 33%, respectively. Low and high doses of tadalafil, vardenafil, and sildenafil inhibited the activity of NADPH-cytochrome c reductase as well as its protein expression. In addition, such drugs inhibited the expression of CYP B1/2 along with its corresponding enzyme marker ECOD activity. It is concluded that changes in the expression and activity of phase I drug-metabolising enzymes could change the normal metabolic pathways and might enhance the deleterious effects of exogenous as well as endogenous compounds. Hindawi Publishing Corporation 2016 2016-10-09 /pmc/articles/PMC5075309/ /pubmed/27800121 http://dx.doi.org/10.1155/2016/4970906 Text en Copyright © 2016 Salah A. Sheweita et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Sheweita, Salah A.
Wally, Mona
Hassan, Mostafa
Erectile Dysfunction Drugs Changed the Protein Expressions and Activities of Drug-Metabolising Enzymes in the Liver of Male Rats
title Erectile Dysfunction Drugs Changed the Protein Expressions and Activities of Drug-Metabolising Enzymes in the Liver of Male Rats
title_full Erectile Dysfunction Drugs Changed the Protein Expressions and Activities of Drug-Metabolising Enzymes in the Liver of Male Rats
title_fullStr Erectile Dysfunction Drugs Changed the Protein Expressions and Activities of Drug-Metabolising Enzymes in the Liver of Male Rats
title_full_unstemmed Erectile Dysfunction Drugs Changed the Protein Expressions and Activities of Drug-Metabolising Enzymes in the Liver of Male Rats
title_short Erectile Dysfunction Drugs Changed the Protein Expressions and Activities of Drug-Metabolising Enzymes in the Liver of Male Rats
title_sort erectile dysfunction drugs changed the protein expressions and activities of drug-metabolising enzymes in the liver of male rats
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5075309/
https://www.ncbi.nlm.nih.gov/pubmed/27800121
http://dx.doi.org/10.1155/2016/4970906
work_keys_str_mv AT sheweitasalaha erectiledysfunctiondrugschangedtheproteinexpressionsandactivitiesofdrugmetabolisingenzymesintheliverofmalerats
AT wallymona erectiledysfunctiondrugschangedtheproteinexpressionsandactivitiesofdrugmetabolisingenzymesintheliverofmalerats
AT hassanmostafa erectiledysfunctiondrugschangedtheproteinexpressionsandactivitiesofdrugmetabolisingenzymesintheliverofmalerats