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Acta Tropica Oct 2022Neurocysticercosis (NCC) is an endemic public health disease of the central nervous system highly related to epilepsy and seizures. Taenia crassiceps is an experimental...
Neurocysticercosis (NCC) is an endemic public health disease of the central nervous system highly related to epilepsy and seizures. Taenia crassiceps is an experimental model used for NCC and biochemical studies of the host-parasite relationship. For the past 50 years the NCC therapeutic treatment is performed with albendazole (ABZ) and praziquantel which opens a gap for new therapies due to parasitic resistance and other adverse effects of the drugs. Oxfendazole (OXF) is an albendazole derivative with efficacy against tissue cestodes of veterinary importance. The aim of this study was to determine the metabolic impact of OXF on T. crassiceps cysticerci intracranially inoculated in Balb/C mice. The animals were intracranially inoculated with T. crassiceps cysticerci and 30 days later received single dose oral treatment of OXF, ABZ and NaCl 0.9% (control group). The metabolic impact was quantified through the detection of metabolites from glycolysis, anaerobic fermentation of lactate and propionate, tricarboxylic acid cycle, protein catabolism, fatty acids oxidation. The differences observed in the concentrations of metabolites from the OXF treated group showed that the drug induced gluconeogenesis, increase in protein catabolism, fatty acids oxidation and propionate fermentation in comparison to the ABZ and control treated groups. In conclusion, OXF induced greater metabolic impact in T. crassiceps cysticerci than the standard NCC treatment, ABZ, showing that it may represent an alternative drug for its treatment.
Topics: Albendazole; Animals; Anthelmintics; Benzimidazoles; Cysticercus; Gluconeogenesis; Mice; Mice, Inbred BALB C; Neurocysticercosis; Propionates; Taenia
PubMed: 35752205
DOI: 10.1016/j.actatropica.2022.106571 -
The Journal of Biological Chemistry Jul 1962
Topics: Lipid Metabolism; Propionates; Sulfonium Compounds
PubMed: 13901535
DOI: No ID Found -
The Science of the Total Environment Jan 2023To meet the increasing demand for meat and milk, the livestock industry has to increase its production. Without improving its efficiency, increased livestock, especially... (Review)
Review
To meet the increasing demand for meat and milk, the livestock industry has to increase its production. Without improving its efficiency, increased livestock, especially ruminant animals, will worsen the environmental damage, mainly from enteric CH emission. Enteric CH emission from ruminants not only exacerbates the global greenhouse effect but also reduces feed energy efficiency for the animals. The rumen disposes of metabolic hydrogen ([H]) primarily through methanogenesis and propionate formation. Theoretically, redirecting [H] from methanogenesis to propionate formation to reduce CH production could be a promising method for reducing greenhouse gas emission from ruminants, and may also increase animal productivity. However, the feasibility of such a shifting has never been synthetically discussed. Thus, the objectives of this review are to provide a brief overview of the biochemical pathways for disposal of H in the rumen, to analyze current feeding strategies that potentially promote propionate formation and their effects on methanogenesis, and to deliberate the challenge and opportunity associated with propionate formation as a sink to store the [H] shifting from enteric CH inhibition.
Topics: Animals; Methane; Propionates; Ruminants; Rumen; Greenhouse Gases; Livestock; Diet
PubMed: 36122712
DOI: 10.1016/j.scitotenv.2022.158867 -
Journal of Dental Research May 2023Oral lichen planus (OLP) and recurrent aphthous stomatitis (RAS) are common chronic inflammatory conditions, manifesting as painful oral lesions that negatively affect...
Oral lichen planus (OLP) and recurrent aphthous stomatitis (RAS) are common chronic inflammatory conditions, manifesting as painful oral lesions that negatively affect patients' quality of life. Current treatment approaches are mainly palliative and often ineffective due to inadequate contact time of the therapeutic agent with the lesions. Here, we developed the Dental Tough Adhesive (DenTAl), a bioinspired adhesive patch with robust mechanical properties, capable of strong adhesion against diverse wet and dynamically moving intraoral tissues, and extended drug delivery of clobetasol-17-propionate, a first-line drug for treating OLP and RAS. DenTAl was found to have superior physical and adhesive properties compared to existing oral technologies, with ~2 to 100× adhesion to porcine keratinized gingiva and ~3 to 15× stretchability. Clobetasol-17-propionate incorporated into the DenTAl was released in a tunable sustained manner for at least 3 wk and demonstrated immunomodulatory capabilities , evidenced by reductions in several cytokines, including TNF-α, IL-6, IL-10, MCP-5, MIP-2, and TIMP-1. Our findings suggest that DenTAl may be a promising device for intraoral delivery of small-molecule drugs applicable to the management of painful oral lesions associated with chronic inflammatory conditions.
Topics: Animals; Swine; Clobetasol; Hydrogels; Quality of Life; Propionates; Dental Cements; Chronic Disease; Lichen Planus, Oral
PubMed: 36883653
DOI: 10.1177/00220345221148684 -
Gut Microbes 2022The bacteria-derived short-chain fatty acids (SCFAs) butyrate and propionate play important (distinct) roles in health and disease, and understanding the ecology of...
The bacteria-derived short-chain fatty acids (SCFAs) butyrate and propionate play important (distinct) roles in health and disease, and understanding the ecology of respective bacteria on a community-wide level is a top priority in microbiome research. Applying sequence data (metagenomics and 16S rRNA gene) to predict SCFAs production and , a clear split between butyrate- and propionate-forming bacteria was detected with only very few taxa exhibiting pathways for the production of both SCFAs. After growth of fecal communities from distinct donors (n = 8) on different substrates (n = 7), abundances of bacteria exhibiting pathways correlated with respective SCFA concentrations, in particular in the case of butyrate. For propionate, correlations were weaker, indicating that its production is less imprinted into the core metabolism compared with butyrate-forming bacteria. Longitudinal measurements (n = 5 time-points from 20 subjects) also revealed a correlation between abundances of pathway-carrying bacteria and concentrations of the two SCFAs. Additionally, lower bacterial cell concentrations, together with higher stool moisture, promoted overall bacterial activity (measured by flow cytometry and coverage patterns of metagenome-assembled genomes) that led to elevated SCFA concentrations with over-proportional levels of butyrate. Predictions on pathway abundances based on 16S rRNA gene data using our in-house database worked well, yielding similar results as metagenomic-based analyses. Our study indicates that stimulating growth of butyrate- and propionate-producing bacteria directly leads to more production of those compounds, which is governed by two functionally distinct bacterial groups facilitating the development of precision intervention strategies targeting either metabolite.
Topics: Humans; Gastrointestinal Microbiome; Butyrates; Propionates; RNA, Ribosomal, 16S; Fatty Acids, Volatile; Bacteria
PubMed: 36416760
DOI: 10.1080/19490976.2022.2149019 -
Journal of Psychiatric Research Dec 2022Short-chain fatty acids (SCFAs), produced during bacterial fermentation, have been shown to be mediators in the microbiota-gut-brain axis. This axis has been proposed to...
Short-chain fatty acids (SCFAs), produced during bacterial fermentation, have been shown to be mediators in the microbiota-gut-brain axis. This axis has been proposed to influence psychiatric symptoms seen in attention deficit hyperactivity disorder (ADHD). However, there is no report of plasma SCFA concentrations in ADHD. The aim of this study was to explore the plasma concentrations of SCFAs in children and adults with ADHD and the possible factors that could influence those levels. We collected data on age group, sex, serum vitamin D levels, delivery mode, body mass index, diet, medication and blood samples from 233 ADHD patients and 36 family-related healthy controls. The concentrations of SCFAs and the intermediary metabolite succinic acid, were measured using liquid chromatography-mass spectrometry. Adults with ADHD had lower plasma concentrations of formic, acetic, propionic and succinic acid than their healthy family members. When adjusting for SCFA-influential factors among those with ADHD, children had lower concentrations of formic, propionic and isovaleric acid than adults, and those who had more antibiotic medications during the last 2 years had lower concentrations of formic, propionic and succinic acid. When adjusting for antibiotic medication, we found that among children, those currently on stimulant medication had lower acetic and propionic acid levels, and adults with ADHD had lower formic and propionic acid concentrations than adult healthy family members. In all, our findings show lower-than-normal plasma concentrations of SCFAs in ADHD explained in-part by antibiotic medication, age and stimulant medication. Whether or not this is of clinical significance is yet to be explored.
Topics: Child; Humans; Propionates; Attention Deficit Disorder with Hyperactivity; Family; Succinates
PubMed: 36228390
DOI: 10.1016/j.jpsychires.2022.09.042 -
IUBMB Life Sep 20133-Nitropropionate (3-NPA) is a nitro aliphatic compound found in numerous plants and fungi. The nitro compound exists in equilibrium with its conjugate base, propionate... (Review)
Review
3-Nitropropionate (3-NPA) is a nitro aliphatic compound found in numerous plants and fungi. The nitro compound exists in equilibrium with its conjugate base, propionate 3-nitronate (P3N) and has a pKa approaching the physiological range of 9.1. Since 1920, more than 30 species of plant and fungi have been identified as producing 3-NPA as a means of defense from herbivores. Glycoside products containing moieties of 3-NPA found in parts of the plants most accessible to herbivores can be easily hydrolyzed to free 3-NPA by bacterial enzymes in the gut of animals. In addition to providing a defense mechanism, the nitro compound is an intermediate in the nitrification process of leguminous plants. The synthesis of 3-NPA in these plants and fungi is poorly understood. P3N, which readily forms from 3-NPA at physiological pH, is a potent inhibitor of the key enzyme succinate dehydrogenase in the Krebs cycle and electron transport chain. Inhibition of succinate dehydrogenase in humans and livestock causes neurotoxicity and in some cases death. Several enzymes catalyze the oxidation of 3-NPA or P3N; all contain a noncovalently bound flavin cofactor and are found in the organisms that produce 3-NPA. With k(cat)/K(m) values of >10(6) M(-1) s(-1), nitronate monooxygenases can quickly and efficiently oxidize P3N to malonic semialdehyde as a means of protecting the organism from killing itself. Although it was discovered almost a century ago, the biochemistry and physiological role of 3-NPA/P3N are just emerging.
Topics: Animals; Fungal Proteins; Humans; Mixed Function Oxygenases; Mycotoxins; Nitro Compounds; Oxidation-Reduction; Plant Proteins; Propionates; Succinate Dehydrogenase
PubMed: 23893873
DOI: 10.1002/iub.1195 -
International Journal of Molecular... Sep 2022Short-chain fatty acids (SCFAs) are potent immune modulators present in the gingival crevicular fluid. It is therefore likely that SCFAs exert a role in periodontal...
Short-chain fatty acids (SCFAs) are potent immune modulators present in the gingival crevicular fluid. It is therefore likely that SCFAs exert a role in periodontal health and disease. To better understand how SCFAs can module inflammation, we screened acetic acid, propionic acid, and butyric acid for their potential ability to lower the inflammatory response of macrophages, gingival fibroblasts, and oral epithelial cells in vitro. To this end, RAW 264.7 and primary macrophages were exposed to LPSs from with and without the SCFAs. Moreover, gingival fibroblasts and HSC2 oral epithelial cells were exposed to IL1β and TNFα with and without the SCFAs. We report here that butyrate was effective in reducing the lipopolysaccharide (LPS)-induced expression of IL6 and chemokine (C-X-C motif) ligand 2 (CXCL2) in the RAW 264.7 and primary macrophages. Butyrate also reduced the IL1β and TNFα-induced expression of IL8, chemokine (C-X-C motif) ligand 1 (CXCL1), and CXCL2 in gingival fibroblasts. Likewise, butyrate lowered the induced expression of CXCL1 and CXCL2, but not IL8, in HSC2 cells. Butyrate further caused a reduction of p65 nuclear translocation in RAW 264.7 macrophages, gingival fibroblasts, and HSC2 cells. Propionate and acetate partially lowered the inflammatory response in vitro but did not reach the level of significance. These findings suggest that not only macrophages, but also gingival fibroblasts and oral epithelial cells are susceptive to the anti-inflammatory activity of butyrate.
Topics: Acetates; Anti-Inflammatory Agents; Butyric Acid; Chemokine CXCL1; Chemokine CXCL2; Fatty Acids, Volatile; Interleukin-6; Lipopolysaccharides; Propionates; Tumor Necrosis Factor-alpha
PubMed: 36232340
DOI: 10.3390/ijms231911006 -
Neurogastroenterology and Motility Dec 2018Propionate exhibits affinity for free fatty acid receptor 2 (FFA2, formerly GPR43) and FFA3 (GPR41). These two G protein-coupled receptors (GPCRs) are expressed by...
BACKGROUND
Propionate exhibits affinity for free fatty acid receptor 2 (FFA2, formerly GPR43) and FFA3 (GPR41). These two G protein-coupled receptors (GPCRs) are expressed by enteroendocrine L cells that contain anorectic peptide YY (PYY) and glucagon-like peptide 1 (GLP-1), while FFA3 is also expressed by enteric neurons. Few studies have investigated the individual roles of FFA2 and FFA3 in propionate's gastrointestinal (GI) effects. Here, we compared FFA2, FFA3, and propionate mucosal responses utilizing selective ligands including an FFA3 antagonist, in mouse and human colonic mucosa.
METHODS
Vectorial ion transport was measured in native colonic preparations from normal mouse and human colon with intact submucosal innervation. Endogenous fecal pellet propulsion was monitored in colons isolated from wild-type (WT) and PYY-/- mice.
KEY RESULTS
FFA2 and FFA3 signaling differed significantly. FFA2 agonism involved endogenous L cell-derived PYY and was glucose dependent, while FFA3 agonism was independent of PYY and glucose, but required submucosal enteric neurons for activity. Tonic FFA3 activity was observed in mouse and human colon mucosa. Apical propionate responses were a combination of FFA2-PYY mediation and FFA3 neuronal GLP-1- and CGRP-dependent signaling in mouse ascending colon mucosa. Propionate also slowed WT and PYY-/- colonic transit, and this effect was blocked by a GLP-1 receptor antagonist.
CONCLUSIONS & INFERENCES
We conclude that luminal propionate costimulates FFA2 and FFA3 pathways, reducing anion secretion and slowing colonic motility; FFA2 via PYY mediation and FFA3 signaling by activation of enteric sensory neurons.
Topics: Animals; Colon; Female; Humans; Intestinal Mucosa; Male; Mice; Mice, Inbred C57BL; Middle Aged; Propionates; Receptors, Cell Surface; Receptors, G-Protein-Coupled; Signal Transduction
PubMed: 30136343
DOI: 10.1111/nmo.13454 -
Nutrients Jun 2023Low-grade inflammation and barrier disruption are increasingly acknowledged for their association with non-communicable diseases (NCDs). Short chain fatty acids (SCFAs),...
Butyrate Protects Barrier Integrity and Suppresses Immune Activation in a Caco-2/PBMC Co-Culture Model While HDAC Inhibition Mimics Butyrate in Restoring Cytokine-Induced Barrier Disruption.
Low-grade inflammation and barrier disruption are increasingly acknowledged for their association with non-communicable diseases (NCDs). Short chain fatty acids (SCFAs), especially butyrate, could be a potential treatment because of their combined anti-inflammatory and barrier- protective capacities, but more insight into their mechanism of action is needed. In the present study, non-activated, lipopolysaccharide-activated and αCD3/CD28-activated peripheral blood mononuclear cells (PBMCs) with and without intestinal epithelial cells (IEC) Caco-2 were used to study the effect of butyrate on barrier function, cytokine release and immune cell phenotype. A Caco-2 model was used to compare the capacities of butyrate, propionate and acetate and study their mechanism of action, while investigating the contribution of lipoxygenase (LOX), cyclooxygenase (COX) and histone deacetylase (HDAC) inhibition. Butyrate protected against inflammatory-induced barrier disruption while modulating inflammatory cytokine release by activated PBMCs (interleukin-1 beta↑, tumor necrosis factor alpha↓, interleukin-17a↓, interferon gamma↓, interleukin-10↓) and immune cell phenotype (regulatory T-cells↓, T helper 17 cells↓, T helper 1 cells↓) in the PBMC/Caco-2 co-culture model. Similar suppression of immune activation was shown in absence of IEC. Butyrate, propionate and acetate reduced inflammatory cytokine-induced IEC activation and, in particular, butyrate was capable of fully protecting against cytokine-induced epithelial permeability for a prolonged period. Different HDAC inhibitors could mimic this barrier-protective effect, showing HDAC might be involved in the mechanism of action of butyrate, whereas LOX and COX did not show involvement. These results show the importance of sufficient butyrate levels to maintain intestinal homeostasis.
Topics: Humans; Cytokines; Butyrates; Leukocytes, Mononuclear; Coculture Techniques; Histone Deacetylases; Caco-2 Cells; Propionates; Interleukins; Intestinal Mucosa
PubMed: 37375664
DOI: 10.3390/nu15122760