LIVIVO - Search results -

Search results

Result 1 - 10 of total 19

Search options

Article ; Online: Differential Modulatory Effects of Methylmercury (MeHg) on Ahr-regulated Genes in Extrahepatic Tissues of C57BL/6 Mice.

Alqahtani, Mohammed A / El-Ghiaty, Mahmoud A / El-Mahrouk, Sara R / El-Kadi, Ayman O S

2024

Abstract: Methylmercury (MeHg) and 2,3,7,8-tetrachlorodibenzodioxin (TCDD) are potent environmental pollutants implicated in the modulation of xenobiotic-metabolizing enzymes, particularly the cytochrome P450 1 family (CYP1) which is regulated by the aryl ... ...

Abstract	Methylmercury (MeHg) and 2,3,7,8-tetrachlorodibenzodioxin (TCDD) are potent environmental pollutants implicated in the modulation of xenobiotic-metabolizing enzymes, particularly the cytochrome P450 1 family (CYP1) which is regulated by the aryl hydrocarbon receptor (AHR). However, the co-exposure to MeHg and TCDD raises concerns about their potential combined effects, necessitating thorough investigation. The primary objective of this study was to investigate the individual and combined effects of MeHg and TCDD on AHR-regulated CYP1 enzymes in mouse extrahepatic tissues. Therefore, C57BL/6 mice were administrated with MeHg (2.5 mg/kg) in the absence and presence of TCDD (15 μg/kg) for 6 and 24 h. The AHR-regulated CYP1 mRNA and protein expression levels were measured in the heart, lung, and kidney, using RT real-time PCR and western blot, respectively. Interestingly, treatment with MeHg exhibited mainly inhibitory effect, particularly, it decreased the basal level of Cyp1a1 and Cyp1a2 mRNA and protein, and that was more evident at the 24 h time point in kidney followed by heart. Similarly, when mice were co-exposed, MeHg was able to reduce the TCDD-induced Cyp1a1 and Cyp1a2 expression, however, MeHg potentiated kidney Cyp1b1 mRNA expression, opposing the observed change on its protein level. Also, MeHg induced antioxidant NAD(P)H:quinone oxidoreductase (NQO1) mRNA and protein in kidney, while heme-oxygenase (HO-1) mRNA was up-regulated in heart and kidney. In conclusion, this study reveals intricate interplay between MeHg and TCDD on AHR-regulated CYP1 enzymes, with interesting inhibitory effects observed that might be significant for procarcinogen metabolism. Varied responses across tissues highlight the potential implications for environmental health.
Language	English
Publishing date	2024-01-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	445336-0
ISSN	1559-0720 ; 0163-4984
ISSN (online)	1559-0720
ISSN	0163-4984
DOI	10.1007/s12011-023-04050-y
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.B 2323: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Dimethylmonothioarsinic acid (DMMTA

El-Mahrouk, Sara R / El-Ghiaty, Mahmoud A / Alqahtani, Mohammed A / El-Kadi, Ayman O S

Toxicology letters

2024 Volume 394, Page(s) 32–45

Abstract: Dimethylmonothioarsinic acid ( ... ...

Abstract	Dimethylmonothioarsinic acid (DMMTA
MeSH term(s)	Humans ; Animals ; Mice ; Cytochrome P-450 CYP1A1/metabolism ; Arsenic ; Mice, Inbred C57BL ; Cytochrome P-450 Enzyme System ; Polychlorinated Dibenzodioxins/toxicity ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Receptors, Aryl Hydrocarbon/metabolism ; Cacodylic Acid/analogs & derivatives
Chemical Substances	Cytochrome P-450 CYP1A1 (EC 1.14.14.1) ; dimethylmonothioarsinic acid ; Arsenic (N712M78A8G) ; Cytochrome P-450 Enzyme System (9035-51-2) ; Polychlorinated Dibenzodioxins ; RNA, Messenger ; Receptors, Aryl Hydrocarbon ; Cacodylic Acid (AJ2HL7EU8K)
Language	English
Publishing date	2024-02-24
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	433788-8
ISSN	1879-3169 ; 0378-4274
ISSN (online)	1879-3169
ISSN	0378-4274
DOI	10.1016/j.toxlet.2024.02.007
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 1367: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Modulation of cytochrome P450 1A (CYP1A) enzymes by monomethylmonothioarsonic acid (MMMTA

El-Ghiaty, Mahmoud A / Alqahtani, Mohammed A / El-Kadi, Ayman O S

Chemico-biological interactions

2023 Volume 376, Page(s) 110447

Abstract: Inorganic arsenic (iAs) is a natural toxicant which, upon entering the biosphere, undergoes extensive biotransformation and becomes a portal for generating various organic intermediates/products. The chemical diversity of iAs-derived organoarsenicals ( ... ...

Abstract	Inorganic arsenic (iAs) is a natural toxicant which, upon entering the biosphere, undergoes extensive biotransformation and becomes a portal for generating various organic intermediates/products. The chemical diversity of iAs-derived organoarsenicals (oAs) is accompanied by varying degree of toxicity that can be held responsible, at least partly, for the overall health outcome of the originally encountered parent inorganic molecule. Such toxicity may originate from arsenicals ability to modulate cytochrome P450 1A (CYP1A) enzymes, whose activity is critical in activating/detoxifying procarcinogens. In this study, we evaluated the effect of monomethylmonothioarsonic acid (MMMTA
MeSH term(s)	Humans ; Animals ; Mice ; Cytochrome P-450 CYP1A2/metabolism ; Cytochrome P-450 CYP1A1/genetics ; Cytochrome P-450 CYP1A1/metabolism ; Mice, Inbred C57BL ; Cytochrome P-450 Enzyme System/genetics ; Arsenicals/pharmacology ; Polychlorinated Dibenzodioxins/toxicity ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Receptors, Aryl Hydrocarbon/metabolism
Chemical Substances	Cytochrome P-450 CYP1A2 (EC 1.14.14.1) ; Cytochrome P-450 CYP1A1 (EC 1.14.14.1) ; monomethylmonothioarsonic acid ; Cytochrome P-450 Enzyme System (9035-51-2) ; Arsenicals ; Polychlorinated Dibenzodioxins ; RNA, Messenger ; Receptors, Aryl Hydrocarbon
Language	English
Publishing date	2023-03-07
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	218799-1
ISSN	1872-7786 ; 0009-2797
ISSN (online)	1872-7786
ISSN	0009-2797
DOI	10.1016/j.cbi.2023.110447
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 686: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Arsenic trioxide (ATO) up-regulates cytochrome P450 1A (CYP1A) enzymes in murine hepatoma Hepa-1c1c7 cell line.

El-Ghiaty, Mahmoud A / Alqahtani, Mohammed A / El-Kadi, Ayman O S

Environmental toxicology and pharmacology

2023 Volume 101, Page(s) 104214

Abstract: Arsenic trioxide (ATO) is a highly toxic arsenical which has been successfully exploited for treating acute promyelocytic leukemia (APL). Unfortunately, its therapeutic efficacy is accompanied by serious toxicities with undeciphered mechanisms. ... ...

Abstract	Arsenic trioxide (ATO) is a highly toxic arsenical which has been successfully exploited for treating acute promyelocytic leukemia (APL). Unfortunately, its therapeutic efficacy is accompanied by serious toxicities with undeciphered mechanisms. Cytochrome P450 1A (CYP1A) enzymes undergo modulation by arsenicals, with ensuing critical consequences regarding drug clearance or procarcinogen activation. Here, we investigated the potential of ATO to alter basal and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced CYP1A1/1A2 expressions. Mouse-derived hepatoma Hepa-1c1c7 cells were exposed to 0.63, 1.25, and 2.5 μM ATO with or without 1 nM TCDD. ATO increased TCDD-induced CYP1A1/1A2 mRNA, protein, and activity. Constitutively, ATO induced Cyp1a1/1a2 transcripts and CYP1A2 protein. ATO increased AHR nuclear accumulation and subsequently increased XRE-luciferase reporter activity. ATO enhanced CYP1A1 mRNA and protein stabilities. In conclusion, ATO up-regulates CYP1A in Hepa-1c1c7 cells transcriptionally, post-transcriptionally, and post-translationally. Therefore, ATO can be implicated in clearance-related interactions with CYP1A1/1A2 substrates, or in excessive activation of environmental procarcinogens.
MeSH term(s)	Mice ; Animals ; Cytochrome P-450 CYP1A1/genetics ; Cytochrome P-450 CYP1A1/metabolism ; Carcinoma, Hepatocellular/drug therapy ; Carcinoma, Hepatocellular/genetics ; Arsenic Trioxide/pharmacology ; Cytochrome P-450 Enzyme System/metabolism ; Cytochrome P-450 CYP1A2/genetics ; Liver Neoplasms ; Cell Line ; Polychlorinated Dibenzodioxins/toxicity ; RNA, Messenger/genetics ; Receptors, Aryl Hydrocarbon
Chemical Substances	Cytochrome P-450 CYP1A1 (EC 1.14.14.1) ; Arsenic Trioxide (S7V92P67HO) ; Cytochrome P-450 Enzyme System (9035-51-2) ; Cytochrome P-450 CYP1A2 (EC 1.14.14.1) ; Polychlorinated Dibenzodioxins ; RNA, Messenger ; Receptors, Aryl Hydrocarbon
Language	English
Publishing date	2023-07-07
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1318302-3
ISSN	1872-7077 ; 1382-6689
ISSN (online)	1872-7077
ISSN	1382-6689
DOI	10.1016/j.etap.2023.104214
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 4490: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: The Duality of Arsenic Metabolism: Impact on Human Health.

El-Ghiaty, Mahmoud A / El-Kadi, Ayman O S

Annual review of pharmacology and toxicology

2022 Volume 63, Page(s) 341–358

Abstract: Arsenic is a naturally occurring hazardous element that is environmentally ubiquitous in various chemical forms. Upon exposure, the human body initiates an elimination pathway of progressive methylation into relatively less bioreactive and more easily ... ...

Abstract	Arsenic is a naturally occurring hazardous element that is environmentally ubiquitous in various chemical forms. Upon exposure, the human body initiates an elimination pathway of progressive methylation into relatively less bioreactive and more easily excretable pentavalent methylated forms. Given its association with decreasing the internal burden of arsenic with ensuing attenuation of its related toxicities, biomethylation has been applauded for decades as a pure route of arsenic detoxification. However, the emergence of detectable trivalent species with profound toxicity has opened a long-standing debate regarding whether arsenic methylation is a detoxifying or bioactivating mechanism. In this review, we approach the topic of arsenic metabolism from both perspectives to create a complete picture of its potential role in the mitigation or aggravation of various arsenic-related pathologies.
MeSH term(s)	Humans ; Arsenic/toxicity ; Methylation
Chemical Substances	Arsenic (N712M78A8G)
Language	English
Publishing date	2022-09-13
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	196587-6
ISSN	1545-4304 ; 0362-1642
ISSN (online)	1545-4304
ISSN	0362-1642
DOI	10.1146/annurev-pharmtox-051921-020936
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Uf I Zs.170: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Methylmercury (MeHg) transcriptionally regulates NAD(P)H:quinone oxidoreductase 1 (NQO1) in Hepa-1c1c7 cells.

Alqahtani, Mohammed A / El-Ghiaty, Mahmoud A / El-Mahrouk, Sara R / El-Kadi, Ayman O S

Current research in toxicology

2023 Volume 5, Page(s) 100126

Abstract: The detoxification of quinones through NAD(P)H:quinone oxidoreductase (NQO1) is a crucial mechanism to maintain cellular homeostasis. The exposure to heavy metals, specifically methylmercury (MeHg), induces several antioxidant enzymes, including NQO1. ... ...

Abstract	The detoxification of quinones through NAD(P)H:quinone oxidoreductase (NQO1) is a crucial mechanism to maintain cellular homeostasis. The exposure to heavy metals, specifically methylmercury (MeHg), induces several antioxidant enzymes, including NQO1. The nuclear factor erythroid 2-related factor-2 (NRF2) is known to regulate the expression of
Language	English
Publishing date	2023-09-17
Publishing country	Netherlands
Document type	Journal Article
ISSN	2666-027X
ISSN (online)	2666-027X
DOI	10.1016/j.crtox.2023.100126
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Differential modulation of cytochrome P450 enzymes by arsenicals in non-human experimental models.

El-Ghiaty, Mahmoud A / El-Mahrouk, Sara R / Alqahtani, Mohammed A / El-Kadi, Ayman O S

Drug metabolism reviews

2023 Volume 55, Issue 4, Page(s) 405–427

Abstract: Arsenic is a hazardous heavy metalloid that imposes threats to human health globally. It is widely spread throughout the environment in various forms. Arsenic-based compounds are either inorganic compounds (iAs) or organoarsenicals (oAs), where the ... ...

Abstract	Arsenic is a hazardous heavy metalloid that imposes threats to human health globally. It is widely spread throughout the environment in various forms. Arsenic-based compounds are either inorganic compounds (iAs) or organoarsenicals (oAs), where the latter are biotically generated from the former. Exposure to arsenic-based compounds results in varying biochemical derangements in living systems, leading eventually to toxic consequences. One important target for arsenic in biosystems is the network of metabolic enzymes, especially the superfamily of cytochrome P450 enzymes (CYPs) because of their prominent role in both endobiotic and xenobiotic metabolism. Therefore, the alteration of the CYPs by different arsenicals has been actively studied in the last few decades. We have previously summarized the findings of former studies investigating arsenic associated modulation of different CYPs in human experimental models. In this review, we focus on non-human models to get a complete picture about possible CYPs alterations in response to arsenic exposure.
MeSH term(s)	Humans ; Arsenicals/metabolism ; Arsenic/metabolism ; Arsenic/toxicity ; Cytochrome P-450 Enzyme System/metabolism ; Inactivation, Metabolic ; Models, Theoretical
Chemical Substances	Arsenicals ; Arsenic (N712M78A8G) ; Cytochrome P-450 Enzyme System (9035-51-2)
Language	English
Publishing date	2023-09-07
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	184967-0
ISSN	1097-9883 ; 0360-2532 ; 0012-6594
ISSN (online)	1097-9883
ISSN	0360-2532 ; 0012-6594
DOI	10.1080/03602532.2023.2254525
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 1030: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Mercury and methylmercury differentially modulate hepatic cytochrome P450 1A1 and 1A2 in vivo and in vitro.

Alqahtani, Mohammed A / El-Ghiaty, Mahmoud A / El-Kadi, Ayman O S

Journal of biochemical and molecular toxicology

2022 Volume 37, Issue 2, Page(s) e23243

Abstract: The cytochrome P450 1 A (CYP1A) subfamily enzymes are involved in the metabolic activation of several xenobiotics to toxic metabolites and reactive intermediates, resulting ultimately in carcinogenesis. Mercury and halogenated aromatic hydrocarbons (HAHs) ...

Abstract	The cytochrome P450 1 A (CYP1A) subfamily enzymes are involved in the metabolic activation of several xenobiotics to toxic metabolites and reactive intermediates, resulting ultimately in carcinogenesis. Mercury and halogenated aromatic hydrocarbons (HAHs), typified by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), are persistent environmental pollutants involved in the modulation of aryl hydrocarbon receptor (AHR) gene battery, including cytochrome P450 (CYP) genes. We previously investigated the effect of coexposure to either inorganic or organic mercury (Hg
MeSH term(s)	Male ; Mice ; Animals ; Cytochrome P-450 CYP1A1/genetics ; Methylmercury Compounds/toxicity ; Methylmercury Compounds/metabolism ; Mercury/toxicity ; Mercury/metabolism ; Mice, Inbred C57BL ; Liver/metabolism ; Cytochrome P-450 Enzyme System/metabolism ; Polychlorinated Dibenzodioxins/toxicity ; Receptors, Aryl Hydrocarbon/metabolism
Chemical Substances	Cytochrome P-450 CYP1A1 (EC 1.14.14.1) ; Methylmercury Compounds ; Mercury (FXS1BY2PGL) ; Cytochrome P-450 Enzyme System (9035-51-2) ; Polychlorinated Dibenzodioxins ; Receptors, Aryl Hydrocarbon
Language	English
Publishing date	2022-10-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	1410020-4
ISSN	1099-0461 ; 1095-6670
ISSN (online)	1099-0461
ISSN	1095-6670
DOI	10.1002/jbt.23243
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 2201: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: Down-regulation of hepatic cytochromes P450 1A1 and 1A2 by arsenic trioxide (ATO) in vivo and in vitro: A role of heme oxygenase 1.

El-Ghiaty, Mahmoud A / Alqahtani, Mohammed A / El-Kadi, Ayman O S

Chemico-biological interactions

2022 Volume 364, Page(s) 110049

Abstract: Arsenic trioxide (ATO) has evolved from an environmental threat to a successful therapy for acute promyelocytic leukemia (APL) and probably for solid tumors in the future. However, its efficacy comes at a cost of multi-organ toxicity whose mechanism ... ...

Abstract	Arsenic trioxide (ATO) has evolved from an environmental threat to a successful therapy for acute promyelocytic leukemia (APL) and probably for solid tumors in the future. However, its efficacy comes at a cost of multi-organ toxicity whose mechanism remains unresolved. Arsenicals have been reported to modulate cytochrome P450 1A (CYP1A) enzymes, thus modifying activation/detoxification of drugs/procarcinogens. Therefore, this study aimed to investigate the possible effects of ATO on CYP1A1 and CYP1A2, in absence and presence of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) using in vivo and in vitro models. For this purpose, C57BL/6 mice were intraperitoneally injected with 8 mg/kg ATO with or without 15 μg/kg TCDD for 6 and 24 h. Furthermore, HepG2 cells were treated with ATO (1, 5, and 10 μM) with or without 1 nM TCDD for 6 and 24 h. ATO significantly inhibited TCDD-mediated induction of CYP1A1/1A2 mRNA, protein, and activity in both models. ATO differentially modulated CYP1A1/1A2 basal levels in vivo. We also demonstrated that ATO downregulates CYP1A through inhibiting the transcriptional activation of its regulatory element at both basal and inducible levels. Additionally, ATO significantly induced mRNA and protein of heme oxygenase 1 (HMOX1) in vivo and in vitro. In HepG2 cells, inhibition of HMOX1 by tin (IV) mesoporphyrin (IX) (SnMP) resulted in a partial restoration of the TCDD-mediated induction of CYP1A1 activity that was inhibited by ATO co-exposure. Our findings show that ATO alters both constitutive and inducible CYP1A1/1A2 expressions through transcriptional and HMOX1-mediated post-translational mechanisms. This implies the possible involvement of ATO in clearance-related consequences for the substrates of these enzymes such as drug-drug interactions or suboptimal toxicant elimination.
MeSH term(s)	Animals ; Arsenic Trioxide/pharmacology ; Cytochrome P-450 CYP1A1/genetics ; Cytochrome P-450 CYP1A1/metabolism ; Cytochrome P-450 CYP1A2/metabolism ; Cytochrome P-450 Enzyme System/metabolism ; Down-Regulation ; Heme Oxygenase-1/metabolism ; Mice ; Mice, Inbred C57BL ; Polychlorinated Dibenzodioxins/toxicity ; RNA, Messenger
Chemical Substances	Polychlorinated Dibenzodioxins ; RNA, Messenger ; Cytochrome P-450 Enzyme System (9035-51-2) ; Cytochrome P-450 CYP1A1 (EC 1.14.14.1) ; Cytochrome P-450 CYP1A2 (EC 1.14.14.1) ; Heme Oxygenase-1 (EC 1.14.14.18) ; Arsenic Trioxide (S7V92P67HO)
Language	English
Publishing date	2022-07-21
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	218799-1
ISSN	1872-7786 ; 0009-2797
ISSN (online)	1872-7786
ISSN	0009-2797
DOI	10.1016/j.cbi.2022.110049
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 686: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Identifying novel aryl hydrocarbon receptor (AhR) modulators from clinically approved drugs: In silico screening and In vitro validation.

Mosa, Farag E S / Alqahtani, Mohammed A / El-Ghiaty, Mahmoud A / Barakat, Khaled / El-Kadi, Ayman O S

Archives of biochemistry and biophysics

2024 Volume 754, Page(s) 109958

Abstract: The aryl hydrocarbon receptor (AhR) functions as a vital ligand-activated transcription factor, governing both physiological and pathophysiological processes. Notably, it responds to xenobiotics, leading to a diverse array of outcomes. In the context of ... ...

Abstract	The aryl hydrocarbon receptor (AhR) functions as a vital ligand-activated transcription factor, governing both physiological and pathophysiological processes. Notably, it responds to xenobiotics, leading to a diverse array of outcomes. In the context of drug repurposing, we present here a combined approach of utilizing structure-based virtual screening and molecular dynamics simulations. This approach aims to identify potential AhR modulators from Drugbank repository of clinically approved drugs. By focusing on the AhR PAS-B binding pocket, our screening protocol included binding affinities calculations, complex stability, and interactions within the binding site as a filtering method. Comprehensive evaluations of all DrugBank small molecule database revealed ten promising hits. This included flibanserin, butoconazole, luliconazole, naftifine, triclabendazole, rosiglitazone, empagliflozin, benperidol, nebivolol, and zucapsaicin. Each exhibiting diverse binding behaviors and remarkably very low binding free energy. Experimental studies further illuminated their modulation of AhR signaling, and showing that they are consistently reducing AhR activity, except for luliconazole, which intriguingly enhances the AhR activity. This work demonstrates the possibility of using computational modelling as a quick screening tool to predict new AhR modulators from extensive drug libraries. Importantly, these findings hold immense therapeutic potential for addressing AhR-associated disorders. Consequently, it offers compelling prospects for innovative interventions through drug repurposing.
MeSH term(s)	Receptors, Aryl Hydrocarbon/metabolism ; Binding Sites ; Protein Binding ; Protein Domains ; Ligands
Chemical Substances	Receptors, Aryl Hydrocarbon ; Ligands
Language	English
Publishing date	2024-03-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	523-x
ISSN	1096-0384 ; 0003-9861
ISSN (online)	1096-0384
ISSN	0003-9861
DOI	10.1016/j.abb.2024.109958
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Uc I Zs.237: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

To top

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito