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International Journal of Molecular... Jun 2024Ibogaine is an organic indole alkaloid that is used in alternative medicine to combat addiction. Numerous cases of life-threatening complications and sudden deaths...
Ibogaine is an organic indole alkaloid that is used in alternative medicine to combat addiction. Numerous cases of life-threatening complications and sudden deaths associated with ibogaine use have been reported, and it has been hypothesized that the adverse effects are related to ibogaine's tendency to induce cardiac arrhythmias. Considering that the bioavailability of ibogaine and its primary metabolite noribogaine is two to three times higher in female rats than in male rats, we here investigated the effect of a single oral dose (1 or 20 mg/kg) of ibogaine on cardiac histopathology and oxidative/antioxidant balance. Our results show that ibogaine induced dose-dependent cardiotoxic necrosis 6 and 24 h after treatment and that this necrosis was not a consequence of inflammation. In addition, no consistent dose- and time-dependent changes in antioxidant defense or indicators of oxidative damage were observed. The results of this study may contribute to a better understanding of ibogaine-induced cardiotoxicity, which is one of the main side effects of ibogaine use in humans and is often fatal. Nevertheless, based on this experiment, it is not possible to draw a definitive conclusion regarding the role of redox processes or oxidative stress in the occurrence of cardiotoxic necrosis after ibogaine administration.
Topics: Animals; Ibogaine; Necrosis; Rats; Oxidation-Reduction; Oxidative Stress; Male; Female; Cardiotoxicity; Antioxidants; Myocardium; Rats, Wistar
PubMed: 38928231
DOI: 10.3390/ijms25126527 -
International Journal of Molecular... Jun 2024Methionine oxidation to the sulfoxide form (MS) is a poorly understood post-translational modification of proteins associated with non-specific chemical oxidation from...
Methionine Sulfoxide Speciation in Mouse Hippocampus Revealed by Global Proteomics Exhibits Age- and Alzheimer's Disease-Dependent Changes Targeted to Mitochondrial and Glycolytic Pathways.
Methionine oxidation to the sulfoxide form (MS) is a poorly understood post-translational modification of proteins associated with non-specific chemical oxidation from reactive oxygen species (ROS), whose chemistries are linked to various disease pathologies, including neurodegeneration. Emerging evidence shows MS site occupancy is, in some cases, under enzymatic regulatory control, mediating cellular signaling, including phosphorylation and/or calcium signaling, and raising questions as to the speciation and functional nature of MS across the proteome. The 5XFAD lineage of the C57BL/6 mouse has well-defined Alzheimer's and aging states. Using this model, we analyzed age-, sex-, and disease-dependent MS speciation in the mouse hippocampus. In addition, we explored the chemical stability and statistical variance of oxidized peptide signals to understand the needed power for MS-based proteome studies. Our results identify mitochondrial and glycolytic pathway targets with increases in MS with age as well as neuroinflammatory targets accumulating MS with AD in proteome studies of the mouse hippocampus. Further, this paper establishes a foundation for reproducible and rigorous experimental MS-omics appropriate for novel target identification in biological discovery and for biomarker analysis in ROS and other oxidation-linked diseases.
Topics: Animals; Alzheimer Disease; Hippocampus; Glycolysis; Mice; Mitochondria; Proteomics; Methionine; Mice, Inbred C57BL; Aging; Male; Female; Oxidation-Reduction; Proteome; Reactive Oxygen Species; Disease Models, Animal
PubMed: 38928221
DOI: 10.3390/ijms25126516 -
International Journal of Molecular... Jun 2024There is a "popular" belief that a fat-free diet is beneficial, supported by the scientific dogma indicating that high levels of fatty acids promote many pathological... (Review)
Review
There is a "popular" belief that a fat-free diet is beneficial, supported by the scientific dogma indicating that high levels of fatty acids promote many pathological metabolic, cardiovascular, and neurodegenerative conditions. This dogma pressured scientists not to recognize the essential role of fatty acids in cellular metabolism and focus on the detrimental effects of fatty acids. In this work, we critically review several decades of studies and recent publications supporting the critical role of mitochondrial fatty acid metabolism in cellular homeostasis and many pathological conditions. Fatty acids are the primary fuel source and essential cell membrane building blocks from the origin of life. The essential cell membranes phospholipids were evolutionarily preserved from the earlier bacteria in human subjects. In the past century, the discovery of fatty acid metabolism was superseded by the epidemic growth of metabolic conditions and cardiovascular diseases. The association of fatty acids and pathological conditions is not due to their "harmful" effects but rather the result of impaired fatty acid metabolism and abnormal lifestyle. Mitochondrial dysfunction is linked to impaired metabolism and drives multiple pathological conditions. Despite metabolic flexibility, the loss of mitochondrial fatty acid oxidation cannot be fully compensated for by other sources of mitochondrial substrates, such as carbohydrates and amino acids, resulting in a pathogenic accumulation of long-chain fatty acids and a deficiency of medium-chain fatty acids. Despite popular belief, mitochondrial fatty acid oxidation is essential not only for energy-demanding organs such as the heart, skeletal muscle, and kidneys but also for metabolically "inactive" organs such as endothelial and epithelial cells. Recent studies indicate that the accumulation of long-chain fatty acids in specific organs and tissues support the impaired fatty acid oxidation in cell- and tissue-specific fashion. This work, therefore, provides a basis to challenge these established dogmas and articulate the need for a paradigm shift from the "pathogenic" role of fatty acids to the critical role of fatty acid oxidation. This is important to define the causative role of impaired mitochondrial fatty acid oxidation in specific pathological conditions and develop novel therapeutic approaches targeting mitochondrial fatty acid metabolism.
Topics: Humans; Fatty Acids; Mitochondria; Animals; Oxidation-Reduction; Lipid Metabolism; Energy Metabolism; Cardiovascular Diseases
PubMed: 38928204
DOI: 10.3390/ijms25126498 -
International Journal of Molecular... Jun 2024Cobalt-aluminum-layered double hydroxides containing carboxymethyl β-cyclodextrin (CMβCD) were synthesized by coprecipitation and evaluated as a cobalt source for the...
Cobalt-aluminum-layered double hydroxides containing carboxymethyl β-cyclodextrin (CMβCD) were synthesized by coprecipitation and evaluated as a cobalt source for the 4-nitrophenol reduction in an aqueous medium. Several physicochemical techniques (XRD, FTIR, TGA) indicated the intercalation of the anionic cyclodextrin without damages to the hydrotalcite-type structure. These lamellar cobalt-aluminum hybrid materials (CoAl_CMβCD) were evaluated in the 4-nitrophenol reduction and showed higher activities in comparison with the CMβCD-free standard material (CoAl_CO). To rationalize these results, a set of experimental controls going from physical mixtures of CoAl_CO with different cyclodextrins to other cobalt-based materials were investigated, highlighting the beneficial effects of both the layered double hydroxide and CMβCD-based hybrid structures. CMβCD also showed a beneficial effect as an additive during the 4-nitrophenol reduction. CoAl_CO, dispersed in a fresh CMβCD solution could be re-used for five successive cycles without the loss of activity.
Topics: Nitrophenols; Cobalt; beta-Cyclodextrins; Hydroxides; Oxidation-Reduction; Catalysis; X-Ray Diffraction; Spectroscopy, Fourier Transform Infrared
PubMed: 38928099
DOI: 10.3390/ijms25126390 -
International Journal of Molecular... Jun 2024Olive oil phenols are recognized as molecules with numerous positive health effects, many of which rely on their antioxidative activity, i.e., the ability to transfer...
Olive oil phenols are recognized as molecules with numerous positive health effects, many of which rely on their antioxidative activity, i.e., the ability to transfer hydrogen to radicals. Proton-coupled electron transfer reactions and hydrogen tunneling are ubiquitous in biological systems. Reactions of olive oil phenols, hydroxytyrosol, tyrosol, oleuropein, oleacein, oleocanthal, homovanillyl alcohol, vanillin, and a few phenolic acids with a DPPH• (2,2-diphenyl-1-picrylhydrazyl) radical in a 1,4-dioxane:water = 95:5 or 99:1 / solvent mixture were studied through an experimental kinetic analysis and computational chemistry calculations. The highest rate constants corresponding to the highest antioxidative activity are obtained for the ortho-diphenols hydroxytyrosol, oleuropein, and oleacein. The experimentally determined kinetic isotope effects (KIEs) for hydroxytyrosol, homovanillyl alcohol, and caffeic acid reactions are 16.0, 15.4, and 16.7, respectively. Based on these KIEs, thermodynamic activation parameters, and an intrinsic bond orbital (IBO) analysis along the IRC path calculations, we propose a proton-coupled electron transfer mechanism. The average local ionization energy and electron donor Fukui function obtained for the phenolic compounds show that the most reactive electron-donating sites are associated with electrons above and below the aromatic ring, in support of the IBO analysis and proposed PCET reaction mechanism. Large KIEs and isotopic values of Arrhenius pre-exponential factor / determined for the hydroxytyrosol, homovanillyl alcohol, and caffeic acid reactions of 0.6, 1.3, and 0.3, respectively, reveal the involvement of hydrogen tunneling in the process.
Topics: Olive Oil; Hydrogen; Phenols; Electron Transport; Protons; Kinetics; Thermodynamics; Antioxidants
PubMed: 38928048
DOI: 10.3390/ijms25126341 -
Biomolecules Jun 2024Lipid peroxidation plays an important role in various pathologies and aging, at least partially mediated by ferroptosis. The role of mitochondrial lipid peroxidation...
Lipid peroxidation plays an important role in various pathologies and aging, at least partially mediated by ferroptosis. The role of mitochondrial lipid peroxidation during ferroptosis remains poorly understood. We show that supplementation of exogenous iron in the form of ferric ammonium citrate at submillimolar doses induces production of reactive oxygen species (ROS) and lipid peroxidation in mitochondria that precede ferroptosis in H9c2 cardiomyocytes. The mitochondria-targeted antioxidant SkQ1 and the redox mediator methylene blue, which inhibits the production of ROS in complex I of the mitochondrial electron transport chain, prevent both mitochondrial lipid peroxidation and ferroptosis. SkQ1 and methylene blue also prevented accumulation of lipofuscin observed after 24 h incubation of cardiomyocytes with ferric ammonium citrate. Using isolated cardiac mitochondria as an in vitro ferroptosis model, it was shown that rotenone (complex I inhibitor) in the presence of ferrous iron stimulates lipid peroxidation and lipofuscin accumulation. Our data indicate that ROS generated in complex I stimulate mitochondrial lipid peroxidation, lipofuscin accumulation, and ferroptosis induced by exogenous iron.
Topics: Lipid Peroxidation; Ferroptosis; Lipofuscin; Myocytes, Cardiac; Animals; Rats; Reactive Oxygen Species; Iron; Cell Line; Quaternary Ammonium Compounds; Mitochondria; Methylene Blue; Mitochondria, Heart; Ferric Compounds; Plastoquinone
PubMed: 38927133
DOI: 10.3390/biom14060730 -
Biomolecules May 2024Microbiota tryptophan metabolism and the biosynthesis of indole derivatives play an important role in homeostasis and pathogenesis in the human body and can be affected...
Microbiota tryptophan metabolism and the biosynthesis of indole derivatives play an important role in homeostasis and pathogenesis in the human body and can be affected by the gut microbiota. However, studies on the interplay between gut microbiota and tryptophan metabolites in patients undergoing dialysis are lacking. This study aimed to identify the gut microbiota, the indole pathway in tryptophan metabolism, and significant functional differences in ESRD patients with regular hemodialysis. We performed the shotgun metagenome sequencing of stool samples from 85 hemodialysis patients. Using the linear discriminant analysis effect size (LEfSe), we examined the composition of the gut microbiota and metabolic features across varying concentrations of tryptophan and indole metabolites. Higher tryptophan levels promoted tyrosine degradation I and pectin degradation I metabolic modules; lower tryptophan levels were associated with glutamate degradation I, fructose degradation, and valine degradation modules. Higher 3-indoxyl sulfate concentrations were characterized by alanine degradation I, anaerobic fatty acid beta-oxidation, sulfate reduction, and acetyl-CoA to crotonyl-CoA. Contrarily, lower 3-indoxyl sulfate levels were related to propionate production III, arabinoxylan degradation, the Entner-Doudoroff pathway, and glutamate degradation II. The present study provides a better understanding of the interaction between tryptophan, indole metabolites, and the gut microbiota as well as their gut metabolic modules in ESRD patients with regular hemodialysis.
Topics: Humans; Gastrointestinal Microbiome; Tryptophan; Renal Dialysis; Indoles; Male; Female; Middle Aged; Aged; Kidney Failure, Chronic; Feces; Metabolic Networks and Pathways; Adult; Metagenome
PubMed: 38927027
DOI: 10.3390/biom14060623 -
Nature Communications Jun 2024Borgs are huge extrachromosomal elements (ECE) of anaerobic methane-consuming "Candidatus Methanoperedens" archaea. Here, we used nanopore sequencing to validate...
Borgs are huge extrachromosomal elements (ECE) of anaerobic methane-consuming "Candidatus Methanoperedens" archaea. Here, we used nanopore sequencing to validate published complete genomes curated from short reads and to reconstruct new genomes. 13 complete and four near-complete linear genomes share 40 genes that define a largely syntenous genome backbone. We use these conserved genes to identify new Borgs from peatland soil and to delineate Borg phylogeny, revealing two major clades. Remarkably, Borg genes encoding nanowire-like electron-transferring cytochromes and cell surface proteins are more highly expressed than those of host Methanoperedens, indicating that Borgs augment the Methanoperedens activity in situ. We reconstructed the first complete 4.00 Mbp genome for a Methanoperedens that is inferred to be a Borg host and predicted its methylation motifs, which differ from pervasive TC and CC methylation motifs of the Borgs. Thus, methylation may enable Methanoperedens to distinguish their genomes from those of Borgs. Very high Borg to Methanoperedens ratios and structural predictions suggest that Borgs may be capable of encapsulation. The findings clearly define Borgs as a distinct class of ECE with shared genomic signatures, establish their diversification from a common ancestor with genetic inheritance, and raise the possibility of periodic existence outside of host cells.
Topics: Genome, Archaeal; Methane; Phylogeny; Oxidation-Reduction; Archaea; Nanopore Sequencing; DNA Methylation; Soil Microbiology
PubMed: 38926353
DOI: 10.1038/s41467-024-49548-8 -
Nature Communications Jun 2024Anaerobic, acetogenic bacteria are well known for their ability to convert various one-carbon compounds, promising feedstocks for a future, sustainable biotechnology, to...
Anaerobic, acetogenic bacteria are well known for their ability to convert various one-carbon compounds, promising feedstocks for a future, sustainable biotechnology, to products such as acetate and biofuels. The model acetogen Acetobacterium woodii can grow on CO, formate or methanol, but not on carbon monoxide, an important industrial waste product. Since hydrogenases are targets of CO inhibition, here, we genetically delete the two [FeFe] hydrogenases HydA2 and HydBA in A. woodii. We show that the ∆hydBA/hydA2 mutant indeed grows on CO and produces acetate, but only after a long adaptation period. SNP analyzes of CO-adapted cells reveal a mutation in the HycB2 subunit of the HydA2/HydB2/HydB3/Fdh-containing hydrogen-dependent CO reductase (HDCR). We observe an increase in ferredoxin-dependent CO reduction and vice versa by the HDCR in the absence of the HydA2 module and speculate that this is caused by the mutation in HycB2. In addition, the CO-adapted ∆hydBA/hydA2 mutant growing on formate has a final biomass twice of that of the wild type.
Topics: Acetobacterium; Formates; Carbon Monoxide; Bacterial Proteins; Hydrogenase; Mutation; Carbon Dioxide; Electron Transport; Biomass; Acetates; Polymorphism, Single Nucleotide
PubMed: 38926344
DOI: 10.1038/s41467-024-49680-5 -
Nanomaterials (Basel, Switzerland) Jun 2024The enhancement of carbon-supported components is a crucial factor in augmenting the interplay between carbon-supported and metal-active components in the utilization of...
The enhancement of carbon-supported components is a crucial factor in augmenting the interplay between carbon-supported and metal-active components in the utilization of catalysts for direct ethanol fuel cells (DEFCs). Here, we propose a strategy for designing a catalyst by modifying candle soot (CS) and loading nickel onto ordered carbon soot. The present study aimed to investigate the effect of the Ni nanoparticles content on the electrocatalytic performance of Ni-CS, ultimately leading to the identification of a maximum composition. The presence of an excessive quantity of nickel particles leads to a decrease in the number of active sites within the material, resulting in sluggishness of the electron transfer pathway. The electrocatalyst composed of nickel and carbon support, with a nickel content of 20 wt%, has demonstrated a noteworthy current activity of 18.43 mA/cm, which is three times that of the electrocatalyst with a higher nickel content of 25 wt%. For example, the 20 wt% Ni-CS electrocatalytic activity was found to be good, and it was approximately four times higher than that of 20 wt% Ni-CB (nickel-carbon black). Moreover, the chronoamperometry (CA) test demonstrated a reduction in current activity of merely 65.80% for a 20 wt% Ni-CS electrocatalyst, indicating electrochemical stability. In addition, this demonstrates the great potential of candle soot with Ni nanoparticles to be used as a catalyst in practical applications.
PubMed: 38921918
DOI: 10.3390/nano14121042