Background And Objective: The present study was designed to validate the functional assay that enables rapid screening of therapeutic candidates for their effect on mitochondrial fatty acid oxidation.
Methods: The two whole-cell systems (tissue homogenates and hepatocytes) have been evaluated to monitor the total beta-oxidation flux of physiologically important H-palmitic acid by measurement of tritiated water enrichment in incubations using UPLC coupled on-line to radioactivity monitoring and mass spectrometry.
Results: Our results with several known inhibitors of fatty acid oxidation showed that this simple assay could correctly predict a potential in alteration of mitochondrial function by drug candidates. Since the beta-oxidation of palmitic acid takes place almost exclusively in mitochondria of human hepatocytes, this model can be also utilized to distinguish between the mitochondrial and peroxisomal routes of this essential metabolic pathway in some cases.
Conclusions: The present work offers a new in vitro screen of changes in mitochondrial beta-oxidation by xenobiotics as well as a model to study the mechanism of this pathway.
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http://dx.doi.org/10.1007/s13318-018-0479-5 | DOI Listing |
Adv Sci (Weinh)
January 2025
College of Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi, 030801, China.
Liver disease poses a significant threat to global public health, with arsenic (As) recognized as a major environmental toxin contributing to liver injury. However, the specific mechanisms and the protective effects of α-lipoic acid (LA) remain unclear. Therefore, this study employs network toxicology and network pharmacology to comprehensively analyze the hepatotoxic mechanism of As and the hepatoprotective mechanism of LA, and further verifies the mechanisms of peroxisomal β-oxidation and lipophagy in the process.
View Article and Find Full Text PDFAppl Environ Microbiol
January 2025
Key Laboratory of Agricultural Environmental Microbiology, Ministry of Agriculture, Department of Microbiology, College of Life Sciences, Nanjing Agricultural University, Nanjing, Jiangsu, China.
Unlabelled: High temperature is an unavoidable environmental stress that generally exerts detrimental effects on organisms and has widespread effects on metabolism. Spermidine is an important member of the polyamines family and is involved in a range of abiotic stress responses in plants. Mitochondria play an essential role in cellular homeostasis and are key components of the stress response.
View Article and Find Full Text PDFProbiotics Antimicrob Proteins
January 2025
Department of Gastroenterology & Hepatology, Laboratory of Metabolomics and Drug-induced Liver Injury, Frontiers Science Center for Disease-Related Molecular Network, and State Key Laboratory of Respiratory Health and Multimorbidity, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
Limosilactobacillus reuteri DSM 17938 (L. reuteri DSM 17938) was one of the most widely used probiotics in humans for gastrointestinal disorders, but few studies have investigated its role in drug-induced liver injury (DILI). Here, we evaluated the efficacy of L.
View Article and Find Full Text PDFIntroduction: The infarcted heart is energetically compromised exhibiting a deficient production of adenosine triphosphate (ATP) and the ensuing impaired contractile function. Short-term blockade of the protein S100A9 improves cardiac performance in mice after myocardial infarction (MI). The implications upon ATP production during this process are not known.
View Article and Find Full Text PDFJ Physiol
January 2025
Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.
The mechanisms that drive placental dysfunction in pregnancies complicated by hypoxia and fetal growth restriction remain poorly understood. Changes to mitochondrial respiration contribute to cellular dysfunction in conditions of hypoxia and have been implicated in the pathoaetiology of pregnancy complications, such as pre-eclampsia. We used bespoke isobaric hypoxic chambers and a combination of functional, molecular and imaging techniques to study cellular metabolism and mitochondrial dynamics in sheep undergoing hypoxic pregnancy.
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