Trimethylamine-N-oxide and cerebral stroke risk: A review.

Autor: Dolkar P; Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysuru 570015, Karnataka, India., Deyang T; Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysuru 570015, Karnataka, India., Anand N; Department of Pharmacology, American University of Antigua, College of Medicine, Saint John's, Po Box W-1451, Antigua and Barbuda., Rathipriya AG; Food and Brain Research Foundation, Chennai 600 094, Tamil Nadu, India., Hediyal TA; Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysuru 570015, Karnataka, India; Centre for Experimental Pharmacology and Toxicology, Central Animal Facility, JSS Academy of Higher Education & Research, Mysuru 570015, Karnataka, India., Chandrasekaran V; Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysuru 570015, Karnataka, India; Centre for Experimental Pharmacology and Toxicology, Central Animal Facility, JSS Academy of Higher Education & Research, Mysuru 570015, Karnataka, India., Krishnamoorthy NK; Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysuru 570015, Karnataka, India; Centre for Experimental Pharmacology and Toxicology, Central Animal Facility, JSS Academy of Higher Education & Research, Mysuru 570015, Karnataka, India., Gorantla VR; Department of Biomedical sciences, Research Faculty, West Virginia School of Osteopathic Medicine, Lewisburg, WV 24901, USA., Bishir M; Institute of NeuroImmune Pharmacology and Department of Biological Sciences, Seton Hall University, South Orange, New Jersey 07079, USA., Rashan L; Biodiversity Research Centre, Dohfar University, Salalah, Sultanate of Oman., Chang SL; Institute of NeuroImmune Pharmacology and Department of Biological Sciences, Seton Hall University, South Orange, New Jersey 07079, USA., Sakharkar MK; Drug discovery and Development Research Group, College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada., Yang J; Drug discovery and Development Research Group, College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada. Electronic address: jian.yang@usask.ca., Chidambaram SB; Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysuru 570015, Karnataka, India; Centre for Experimental Pharmacology and Toxicology, Central Animal Facility, JSS Academy of Higher Education & Research, Mysuru 570015, Karnataka, India. Electronic address: saravanababu.c@jssuni.edu.in.
Jazyk: angličtina
Zdroj: Neurobiology of disease [Neurobiol Dis] 2024 Mar; Vol. 192, pp. 106423. Date of Electronic Publication: 2024 Jan 28.
DOI: 10.1016/j.nbd.2024.106423
Abstrakt: Trimethylamine-N-oxide (TMAO) is a gut microbiota-derived metabolite produced by the action of gut microbiota and the hepatic enzyme Flavin Mono‑oxygenase 3 (FMO3). TMAO level has a positive correlation with the risk of cardiovascular events, including stroke, and their level is influenced mainly by dietary choice and the action of liver enzyme FMO3. TMAO plays a role in the development of atherosclerosis plaque, which is one of the causative factors of the stroke event. Preclinical and clinical investigations on the TMAO and associated stroke risk, severity, and outcomes are summarised in this review. In addition, mechanisms of TMAO-driven vascular dysfunction are also discussed, such as inflammation, oxidative stress, thrombus and foam cell formation, altered cholesterol and bile acid metabolism, etc. Post-stroke inflammatory cascades involving activation of immune cells, i.e., microglia and astrocytes, result in Blood-brain-barrier (BBB) disruption, allowing TMAO to infiltrate the brain and further aggravate inflammation. This event occurs as a result of the activation of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome pathway through the release of inflammatory cytokines and chemokines that further aggravate the BBB and initiate further recruitment of immune cells in the brain. Thus, it's likely that maintaining TMAO levels and associated gut microbiota could be a promising approach for treating and improving stroke complications.
Competing Interests: Declaration of competing interest None. The authors declare that there are no conflicts of / or competing interests.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: