Review
Biochemistry & Molecular Biology
Zeqi Shi, Zuowen He, Dao Wen Wang
Summary: Inflammation plays a crucial role in various systemic illnesses, and EETs have been found to have anti-inflammatory effects, reducing inflammation and remodeling of blood vessels. EETs also play important roles in other pathological conditions. Manipulating the AA-CYP450-EETs-sEH pathway has shown potential in alleviating inflammatory diseases, highlighting the importance of this research field.
Review
Pharmacology & Pharmacy
Mohammed A. W. ElKhatib, Fadumo Ahmed Isse, Ayman O. S. El-Kadi
Summary: The incidence of heart failure (HF) is preceded by cardiac hypertrophy (CH). Arachidonic acid (AA) metabolism is modulated during cardiac hypertrophy. Studies have shown that AA metabolites mediated by cytochrome P450 (CYP) play a role in the pathogenesis of cardiac hypertrophy. Inflammation has been found to affect the expression of CYPs and their metabolites in the heart. Pro-inflammatory metabolites such as HETEs are implicated in cardiac hypertrophy, while anti-inflammatory EETs have cardioprotective properties. This review highlights the impact of inflammation on CYP-derived AA metabolites and cardiac hypertrophy, and discusses potential anti-inflammatory strategies for the treatment of cardiac hypertrophy and heart failure.
DRUG METABOLISM REVIEWS
(2023)
Review
Cell Biology
Rebecca Charles, Philip Eaton
Summary: Cell responses to changes in redox state are mediated by reversible protein modifications, which can alter protein activities or interactions. These modifications are crucial for cells' homeostatic responses to environmental changes in redox state. The dysregulation of these redox regulatory mechanisms can contribute to pathophysiology. This review focuses on the redox control of soluble epoxide hydrolase (sEH), its different oxidative modifications, and their impact on cardiovascular physiology and disease progression during stress.
Article
Biochemistry & Molecular Biology
Christophe Morisseau, Sean D. Kodani, Shizuo G. Kamita, Jun Yang, Kin Sing Stephen Lee, Bruce D. Hammock
Summary: Epoxy-fatty acids (EpFAs) are endogenous lipid mediators with diverse biological activities; soluble epoxide hydrolase (sEH) is the primary enzyme for degrading EpFAs in vivo; recent studies suggest that microsomal epoxide hydrolase and epoxide hydrolase-3 also play significant roles in the metabolism of EpFAs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Pharmacology & Pharmacy
John D. Imig, Ludek Cervenka, Jan Neckar
Summary: Coronary artery dysfunction, inflammation, and mitochondrial dysfunction contribute to the progression of heart diseases, and genetic and pharmacological manipulation of epoxylipids has therapeutic benefits.
BIOCHEMICAL PHARMACOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Kanika Verma, Smita Jain, Swati Paliwal, Sarvesh Paliwal, Swapnil Sharma
Summary: This article discusses the importance of Epoxide hydrolase (EH) as a crucial enzyme for catabolism, detoxification, and regulation of signaling molecules, and highlights the potential applications of sEH as a pharmacological target in various diseases. Specifically, it focuses on the development and clinical application of soluble epoxide hydrolase inhibitors (sEHIs) for the management of metabolic syndrome and related disorders.
CURRENT MOLECULAR PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Vengai Mavangira, Matthew J. Kuhn, Angel Abuelo, Christophe Morisseau, Bruce D. Hammock, Lorraine M. Sordillo
Summary: Comparative analysis of sEH activity and oxidant status between healthy dairy cows and those with coliform mastitis revealed increased sEH activity in mammary tissue and elevated oxidant levels in milk of the mastitis group, suggesting potential therapeutic targets for coliform mastitis.
Article
Biochemistry & Molecular Biology
Ami Oguro, Yasuhiro Ishihara, Ferbian Milas Siswanto, Takeshi Yamazaki, Atsuhiko Ishida, Hiromasa Imaishi, Susumu Imaoka
Summary: The study suggests that DHA metabolites, specifically DHDPs generated by P450s and sEH, play an important role in improving rotenone-induced Parkinson's disease. DHA supplementation can improve motor dysfunction in rats and increase the expression of antioxidant genes and Nrf2 protein in the striatum.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2021)
Article
Biochemistry & Molecular Biology
Fawzy Elbarbry, Nicholas Moshirian
Summary: The study demonstrates the antihypertensive effect of honokiol (HON), a naturally occurring polyphenol, and highlights its role in modulating arachidonic acid (AA) metabolism. These findings provide a novel mechanism for the cardioprotective properties of HON.
Article
Medicine, Research & Experimental
Selina T. Somani, Maxwell Zeigler, Emily E. Fay, Maggie Leahy, Bethanee Bermudez, Rheem A. Totah, Mary F. Hebert
Summary: The study found that changes in arachidonic acid metabolites during pregnancy may be associated with the cytochrome P450 pathway, which plays an important role in healthy pregnancy.
Review
Medicine, Research & Experimental
Yanfang Zhang, Liangcai Gao, Bingyi Yao, Shengbo Huang, Yuanjin Zhang, Jie Liu, Zongjun Liu, Xin Wang
Summary: Epoxyeicosatrienoic acids (EETs) play a crucial role in heart function and their metabolic pathway serves as an important target for drug development and prevention of cardiotoxicity, showing promising prospects for cardiovascular disease treatment.
Article
Biochemistry & Molecular Biology
Emmanuelle Pineau, Vincent Sauveplane, Etienne Grienenberger, Jean-Etienne Bassard, Frederic Beisson, Franck Pinot
Summary: Data mining led to the identification and characterization of a new fatty acid epoxygenase in Arabidopsis thaliana, named CYP77B1, capable of converting plant fatty acids into specific diols. The enzyme showed highest expression in flower bud and was mainly present in pistil during open flower stage. The study also suggested a specific function of CYP77B1 in flowering plants based on phylogenetic analysis.
Review
Pharmacology & Pharmacy
Fadumo Ahmed Isse, Ahmed A. El-Sherbeni, Ayman O. S. El-Kadi
Summary: Understanding lipid metabolism is crucial in understanding the pathogenesis of Diabetes Mellitus (DM). The role of P450-derived AA metabolites in DM and diabetic cardiomyopathy highlights their potential as a target for developing new treatments.
DRUG METABOLISM REVIEWS
(2022)
Review
Chemistry, Medicinal
Maryam Nazari, Elham Rezaee, Sayyed Abbas Tabatabai
Summary: Soluble epoxide hydrolase is an enzyme that exists in various organs and tissues and is responsible for degrading epoxyeicosatrienoic acids. Inhibiting this enzyme is a potential strategy for the treatment of renal and cardiovascular diseases, inflammation, and pain. Developing novel inhibitors for soluble epoxide hydrolase has been a popular research topic, but there are challenges such as rapid metabolism and weak pharmacokinetic characteristics.
MINI-REVIEWS IN MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Analytical
Cai-Feng Xiong, Quan-Fei Zhu, Yao-Yu Chen, Dong-Xiao He, Yu-Qi Feng
Summary: In this study, a highly sensitive and specific method for screening and annotating epoxy/dihydroxy-oxylipins in biological samples was established using chemical labeling-assisted liquid chromatography coupled with high-resolution mass spectrometry. The analysis revealed the presence of potential epoxy/dihydroxy-oxylipins, including previously unreported compounds, in human serum and high-fat diet mouse heart samples. Moreover, the method showed a significant decrease in the levels of certain epoxy/dihydroxy-oxylipins in the heart of mice with high-fat diet, particularly those derived from linoleic acid or alpha-linolenic acid.
ANALYTICAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Marianne K. O. Grant, Ibrahim Y. Abdelgawad, Christine A. Lewis, Davis Seelig, Beshay N. Zordoky
Letter
Oncology
Anne Blaes, Suma Konety, Beshay Zordoky
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2021)
Article
Biochemistry & Molecular Biology
Zaid H. Maayah, Abrar S. Alam, Shingo Takahara, Shubham Soni, Mourad Ferdaoussi, Nobutoshi Matsumura, Beshay N. Zordoky, David D. Eisenstat, Jason R. B. Dyck
Summary: DOX is an effective anticancer agent but can cause cardiotoxic effects. Co-treatment with RES can attenuate cardiac injury by reducing systemic inflammation.
Review
Pharmacology & Pharmacy
Ibrahim Y. Abdelgawad, Karim T. Sadak, Diana W. Lone, Mohamed S. Dabour, Laura J. Niedernhofer, Beshay N. Zordoky
Summary: Cancer treatment can accelerate aging and increase the risk of cardiovascular complications. While there are approaches to mitigate therapy-induced senescence, strategies to prevent and treat cardiovascular senescence have not yet been translated to clinical practice.
PHARMACOLOGY & THERAPEUTICS
(2021)
Article
Biochemistry & Molecular Biology
Ibrahim Y. Abdelgawad, Marianne K. O. Grant, Flavia E. Popescu, David A. Largaespada, Beshay N. Zordoky
Summary: DOX is widely used in pediatric oncology and induces inflammatory response; the study found that DOX treatment suppressed tumor growth but caused cardiac atrophy in both tumor-free and tumor-bearing mice; EL4 lymphoma cells elicited inflammatory response in heart, liver, and kidney.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Veterinary Sciences
Kristine Walters, Alessia Stornetta, Foster Jacobs, Peter W. Villalta, Maria Razzoli, Marianne Grant, Beshay Zordoky, Alessandro Bartolomucci, Antonella Borgatti, Silvia Balbo
Summary: This study introduced a novel mass spectrometry approach for identifying doxorubicin-DNA adducts, aiming to personalize chemotherapy protocols for veterinary cancer patients. It also demonstrated the detection capability of doxorubicin and its related molecules in vitro and in vivo, laying the foundation for future biomarker development in veterinary oncology.
BMC VETERINARY RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Ibrahim Y. Abdelgawad, Kevin Agostinucci, Beshay N. Zordoky
Summary: Therapy-induced senescence is a fundamental mechanism contributing to adverse health complications in cancer survivors. This mini-review focuses on the mechanisms of endothelial cell senescence and discusses novel senotherapeutic approaches.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2022)
Article
Cardiac & Cardiovascular Systems
Kevin Agostinucci, Marianne K. O. Grant, Davis Seelig, Dogacan Yucel, Jop van Berlo, Alessandro Bartolomucci, Jason R. B. Dyck, Beshay N. Zordoky
Summary: This study aims to investigate whether pre-exposure to doxorubicin during adolescence would make the heart more susceptible to non-hypertensive pathologic stimuli. The results show that doxorubicin-induced latent cardiotoxicity enhances the cardiac response to hypertensive stimuli and is associated with worsened cardiac function and increased fibrosis.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Cell Biology
Ibrahim Y. Abdelgawad, Kevin Agostinucci, Somia G. Ismail, Marianne K. O. Grant, Beshay N. Zordoky
Summary: The research found that DOX-induced senescence demonstrates similar phenotypes between EA.hy926 cells and HUVECs, but they respond differently to ABT-263.
Article
Multidisciplinary Sciences
Anne H. Blaes, Chandini Nair, Susan Everson-Rose, Patricia Jewett, Jack Wolf, Beshay Zordoky
Summary: The use of aromatase inhibitors (AIs) in breast cancer survivors is associated with higher cardiovascular events and lower endothelial function. Psychosocial stress is associated with increased levels of inflammatory markers and decreased endothelial function in healthy individuals. This study investigated the associations between psychosocial measures and markers of inflammation, aging, and endothelial function in breast cancer survivors on AIs. Positive correlations were observed between psychosocial measures and inflammatory markers, but no associations were found with endothelial function or aging biomarkers. These findings suggest that psychosocial stress may contribute to inflammation in breast cancer survivors on AIs, but further research is needed to understand the relationships between inflammation, aging, and endothelial function in this population.
SCIENTIFIC REPORTS
(2023)
Article
Chemistry, Medicinal
Kevin Agostinucci, Marianne K. O. Grant, Wongel Melaku, Chandini Nair, Beshay N. N. Zordoky
Summary: Sex is an important risk factor in the development of doxorubicin-induced cardiotoxicity. The study found sexual differences in the heart's response to hypertrophic stimuli in doxorubicin-exposed mice. Pre-exposure to doxorubicin caused male-specific cardiac atrophy that persisted after isoproterenol treatment, which could not be prevented by gonadectomy. However, there were no sex differences in the expression of markers of pathological hypertrophy, fibrosis, or inflammation.
Article
Geriatrics & Gerontology
Ibrahim Y. Abdelgawad, Kevin Agostinucci, Bushra Sadaf, Marianne K. O. Grant, Beshay N. Zordoky
Summary: This study demonstrates that metformin can mitigate DOX-induced endothelial cell senescence phenotype and ameliorate the hyper-inflammatory response to LPS. These findings suggest that metformin may protect against DOX-induced vascular aging and endothelial dysfunction and ameliorate infection-induced hyper-inflammation in DOX-treated cancer survivors.
FRONTIERS IN AGING
(2023)
Article
Behavioral Sciences
Marianne K. O. Grant, Maria Razzoli, Ibrahim Y. Abdelgawad, Rachel Mansk, Davis Seelig, Alessandro Bartolomucci, Beshay N. Zordoky
Summary: This study established a mouse model of juvenile DOX-induced cardiotoxicity predisposing to adult-onset stress-induced adverse cardiac remodeling. Results showed that juvenile exposure to DOX followed by adult-onset CSS caused cardiac fibrosis and inflammation, along with upregulated gene expression of multiple inflammatory and fibrotic markers.
STRESS-THE INTERNATIONAL JOURNAL ON THE BIOLOGY OF STRESS
(2022)
Meeting Abstract
Cardiac & Cardiovascular Systems
Marianne K. Grant, Davis Seelig, Ibrahim Abdelgawad, Beshay Zordoky
CIRCULATION RESEARCH
(2020)
Review
Medicine, Research & Experimental
Alexa N. Carrera, Marianne K. O. Grant, Beshay N. Zordoky