Identification of 19-(<i>S/R</i>)Hydroxyeicosatetraenoic Acid as the First Endogenous Noncompetitive Inhibitor of Cytochrome P450 1B1 with Enantioselective Activity

Shoieb, Sherif M.; El-Sherbeni, Ahmed A.; El‐Kadi, Ayman O.S.

doi:10.1124/dmd.118.084657

Cited by 13 publications

(4 citation statements)

References 26 publications

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“…It is protected against angiotensin II-induced cellular hypertrophy by reducing the level of pro-inflammatory midchain HETEs. Also, it noncompetitively inhibited the catalytic activity of CYP1B1, decreased the levels of lipoxygenase and cyclooxygenase-2 enzymes, and decreased the levels of IL-6 and IL-8 [18,101]. Strategies to enhance the levels of subterminal HETEs in the body include using specific CYP modulators such as isoniazid, a well-established inducer of hepatic CYP2E1, that increase the production of endogenous 19-HETE levels as well as using subterminal HETE synthetic analogs [29,30,102].…”

Section: Could the Modulation Of Subterminal Hydroxyeicosatetraenoic mentioning

confidence: 99%

Targeting arachidonic acid–related metabolites in COVID-19 patients: potential use of drug-loaded nanoparticles

Shoieb,

El-Ghiaty,

El-Kadi

2020

emergent mater.

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In March 2020, The World Health Organization (WHO) has declared that the coronavirus disease 2019 (COVID-19) is characterized as a global pandemic. As of September 2020, infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread to 213 countries and territories around the world, affected more than 31.5 million people, and caused more than 970,000 deaths worldwide. Although COVID-19 is a respiratory illness that mainly targets the lungs, it is currently well established that it is a multifactorial disease that affects other extra-pulmonary systems and strongly associated with a detrimental inflammatory response. Evidence has shown that SARS-CoV-2 causes perturbation in the arachidonic acid (AA) metabolic pathways; this disruption could lead to an imbalance between the pro-inflammatory metabolites of AA including mid-chain HETEs and terminal HETE (20-HETE) and the anti-inflammatory metabolites such as EETs and subterminal HETEs. Therefore, we propose novel therapeutic strategies to modulate the level of endogenous anti-inflammatory metabolites of AA and induce the patient’s endogenous resolution mechanisms that will ameliorate the virus-associated systemic inflammation and enhance the primary outcomes in COVID-19 patients. Also, we propose that using nanoencapsulation of AA and its associated metabolites will contribute to the development of safer and more efficacious treatments for the management of COVID-19.

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Section: Could the Modulation Of Subterminal Hydroxyeicosatetraenoic mentioning

confidence: 99%

Targeting arachidonic acid–related metabolites in COVID-19 patients: potential use of drug-loaded nanoparticles

Shoieb,

El-Ghiaty,

El-Kadi

2020

emergent mater.

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“…A major interest of the El-Kadi group is the role of P450s in arachidonic acid metabolism (El-Sherbeni and El-Kadi, 2014) and alterations in these pathways in various disease models including: doxorubicin nephrotoxicity, hepatotoxicity (Zordoky et al, 2011), and cardiotoxicity (Alsaad et al, 2012); isoproterenol-induced cardiac hypertrophy (Zordoky et al, 2008;Althurwi et al, 2015); and angiotensin II-induced cardiac hypertrophy (Shoieb and El-Kadi, 2018;Alammari et al, 2023). Interestingly, this group also showed that 19(S)-hydroxyeicosatetraenoic acid is a more potent endogenous noncompetitive inhibitor of human CYP1B1 than the R-enantiomer (Shoieb et al, 2019).…”

Section: Prairie Provinces (Alberta Saskatchewan Manitoba)mentioning

confidence: 99%

Canadian Content in the Pages ofDrug Metabolism and Disposition: A Comprehensive Historical Analysis

Riddick

2023

Drug Metab Dispos

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Scientists from Canadian institutions have a rich history of making interesting and important contributions to the journal Drug Metabolism and Disposition (DMD) over the past 51 years. A goal of this minireview is to highlight these contributions and pay tribute to many of the scientists at Canadian institutions that have aided in the evolution of the discipline through their DMD publications. We conducted a geographical and research sectoral analysis of the temporal trends of DMD publications originating from Canadian sources. The fraction of total DMD papers of Canadian origin achieved a peak during the 1990s and since that time, this metric has displayed a pronounced and steady decline to the present situation, where the country needs to be concerned about its potentially vulnerable global status within the realm of drug metabolism and disposition science. Stronger and timely investment by Canadian academic institutions in drug metabolism and disposition science may help to restore the nation's research excellence in this discipline and ensure a more robust pipeline of appropriately trained scientists to take on careers in academia, industry, and government. Significance StatementThe substantial contributions made by scientists at Canadian institutions to the journal Drug Metabolism and Disposition (DMD) are highlighted and celebrated in this minireview.Analysis of temporal trends in the fraction of total DMD papers of Canadian origin paints a concerning picture of Canada's current global status in the realm of drug metabolism and disposition science. Further investment in this discipline at Canadian universities may be needed.

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“…Over the last few decades, several studies have shown that the Ep-PUFAs likely act stereospecifically [ 100 , 109 , 110 , 111 ]. In addition to Ep-PUFAs, the biological functions of hydroxy-PUFAs are also stereo- and regioselective [ 22 , 112 , 113 , 114 , 115 ].…”

Section: Cyp: a Key Monooxygenase Enzyme In Pufas Metabolismmentioning

confidence: 99%

Cytochrome P450 Metabolism of Polyunsaturated Fatty Acids and Neurodegeneration

et al. 2020

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Due to the aging population in the world, neurodegenerative diseases have become a serious public health issue that greatly impacts patients’ quality of life and adds a huge economic burden. Even after decades of research, there is no effective curative treatment for neurodegenerative diseases. Polyunsaturated fatty acids (PUFAs) have become an emerging dietary medical intervention for health maintenance and treatment of diseases, including neurodegenerative diseases. Recent research demonstrated that the oxidized metabolites, particularly the cytochrome P450 (CYP) metabolites, of PUFAs are beneficial to several neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease; however, their mechanism(s) remains unclear. The endogenous levels of CYP metabolites are greatly affected by our diet, endogenous synthesis, and the downstream metabolism. While the activity of omega-3 (ω-3) CYP PUFA metabolites and omega-6 (ω-6) CYP PUFA metabolites largely overlap, the ω-3 CYP PUFA metabolites are more active in general. In this review, we will briefly summarize recent findings regarding the biosynthesis and metabolism of CYP PUFA metabolites. We will also discuss the potential mechanism(s) of CYP PUFA metabolites in neurodegeneration, which will ultimately improve our understanding of how PUFAs affect neurodegeneration and may identify potential drug targets for neurodegenerative diseases.

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Identification of 19-(S/R)Hydroxyeicosatetraenoic Acid as the First Endogenous Noncompetitive Inhibitor of Cytochrome P450 1B1 with Enantioselective Activity

Cited by 13 publications

References 26 publications

Targeting arachidonic acid–related metabolites in COVID-19 patients: potential use of drug-loaded nanoparticles

Targeting arachidonic acid–related metabolites in COVID-19 patients: potential use of drug-loaded nanoparticles

Canadian Content in the Pages ofDrug Metabolism and Disposition: A Comprehensive Historical Analysis

Cytochrome P450 Metabolism of Polyunsaturated Fatty Acids and Neurodegeneration

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