The Acute Effect of Trimethylamine-N-Oxide on Vascular Function, Oxidative Stress, and Inflammation in Rat Aortic Rings

Florea, Cristian Marius; Bâldea, Ioana; Roşu, Radu; Moldovan, Remus; Decea, Nicoleta; Filip, Gabriela Adriana

doi:10.1007/s12012-023-09794-6

Cited by 3 publications

(2 citation statements)

References 30 publications

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“…A study done by Yang et al on rats showed that diet supplementation with choline, a TMAO precursor, increased aortic tissue iNOS expression, which was inhibited by nobiletin, a phytochemical with antioxidant properties 49 . We have shown in our previous work that acute exposure of rat aortic rings to different TMAO dosages in an organ bath increased aortic tissue oxidative stress and in ammation, with increased levels of iNOS in a dosedependent manner 50 . At the hepatic level, Lim et al evaluated the effect of antioxidant Black Raspberry (Rubus occidentalis) extract on liver in ammation in a murine experiment.…”

Section: Discussionmentioning

confidence: 87%

The impact of chronic TMAO administration on liver oxidative stress, inflammation, and fibrosis

Florea

Roşu

Moldovan

et al. 2023

Preprint

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Purpose TMAO, a gut microbiota derived byproduct, has been associated with various cardiometabolic diseases by promoting oxidative stress and inflammation. The liver is the main organ for TMAO production and chronic exposure to high doses of TMAO could alter its function. In the present study we evaluated the effect of chronic exposure of high TMAO doses on liver oxidative stress, inflammation and fibrosis. Methods TMAO was administered daily via gastric gavage to 24 male Wistar rats for 3 months. The animals were divided in three groups, a high-dosage group that received 40 mg of TMAO/day, a low-dose group that received 20 mg of TMAO/day and a control group treated with vehicle. Blood was drawn for the quantification of TMAO and liver tissues were harvested for the assessment of oxidative stress (MDA, GSH, GSSG, GPx, CAT, and 8-oxo-dG) and inflammation by quantification of NOS and COX-2 expression. The evaluation of fibrosis was made by western blot analysis of α-SMA and Collagen-3 protein expression. Moreover, histological investigation and immunohistochemical staining of iNOS were performed in order to assess the liver damage. Results After 3 months of TMAO exposure, TMAO serum levels enhanced in parallel with significant increases in MDA and GSSG levels in liver and lower values of GSH and GSH/GSSG ratio as well as significant decrease in GPx and CAT activities. Inflammation was also highlighted, with a significant increase in iNOS and COX-2 expression, but without structural changes and without induction of liver fibrosis. Conclusion Chronic administration of TMAO for 3 months induced liver oxidative stress and inflammation without the appearance of fibrosis or liver structural changes.

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Section: Discussionmentioning

confidence: 87%

The impact of chronic TMAO administration on liver oxidative stress, inflammation, and fibrosis

Florea

Roşu

Moldovan

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

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“…Our interest moved from the widely accepted “gut–heart axis” hypothesis, which assumes a close relationship between gut microbiota-derived metabolites and cardiovascular health [ 33 ]. Indeed, different metabolites from the gut microbiota have already been related to cardiovascular disease (CVD); among all, trimethylamine N-oxide (TMAO) shows possible involvement in endothelial dysfunction [ 9 , 11 , 34 ], and short-chain fatty acids (SCFAs) seem to be involved in the improvement of atherosclerotic burden [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

Indole-3-Propionic Acid, a Gut Microbiota-Derived Tryptophan Metabolite, Promotes Endothelial Dysfunction Impairing Purinergic-Induced Nitric Oxide Release in Endothelial Cells

Geddo,

Antoniotti,

Gallo

et al. 2024

IJMS

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Different gut microbiota-derived metabolites influence cardiovascular function, and, among all, the role of indole-3-propionic acid (IPA), from tryptophan metabolism, shows controversial effects. The aim of this study was to evaluate its role in endothelial dysfunction. IPA effects were studied on bovine aortic endothelial cells (BAE-1). First, IPA cytotoxicity was evaluated by an MTS assay. Then, the levels of intracellular reactive oxygen species (ROS) were evaluated by a microplate reader or fluorescence microscopy with the CellROX® Green probe, and nitric oxide (NO) production was studied by fluorescence microscopy with the DAR4M-AM probe after acute or chronic treatment. Finally, immunoblotting analysis for endothelial nitric oxide synthase (eNOS) phosphorylation (p-eNOS) was performed. In BAE-1, IPA was not cytotoxic, except for the highest concentration (5 mM) after 48 h of treatment, and it showed neither oxidant nor antioxidant activity. However, the physiological concentration of IPA (1 μM) significantly reduced NO released by adenosine triphosphate (ATP)-stimulated BAE-1. These last data were confirmed by Western blot analysis, where IPA induced a significant reduction in p-eNOS in purinergic-stimulated BAE-1. Given these data, we can speculate that IPA negatively affects the physiological control of vascular tone by impairing the endothelial NO release induced by purinergic stimulation. These results represent a starting point for understanding the mechanisms underlying the relationship between gut microbiota metabolites and cardiometabolic health.

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The impact of chronic Trimethylamine N-oxide administration on liver oxidative stress, inflammation, and fibrosis

Florea,

Rosu,

Moldovan

et al. 2024

Food and Chemical Toxicology

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The Acute Effect of Trimethylamine-N-Oxide on Vascular Function, Oxidative Stress, and Inflammation in Rat Aortic Rings

Cited by 3 publications

References 30 publications

The impact of chronic TMAO administration on liver oxidative stress, inflammation, and fibrosis

The impact of chronic TMAO administration on liver oxidative stress, inflammation, and fibrosis

Indole-3-Propionic Acid, a Gut Microbiota-Derived Tryptophan Metabolite, Promotes Endothelial Dysfunction Impairing Purinergic-Induced Nitric Oxide Release in Endothelial Cells

The impact of chronic Trimethylamine N-oxide administration on liver oxidative stress, inflammation, and fibrosis

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