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Biomedicine & Pharmacotherapy =... Dec 2023Long-chain acylcarnitines (LCACs) are intermediates of fatty acid oxidation and are known to exert detrimental effects on mitochondria. This study aimed to test whether...
Long-chain acylcarnitines (LCACs) are intermediates of fatty acid oxidation and are known to exert detrimental effects on mitochondria. This study aimed to test whether lowering LCAC levels with the anti-ischemia compound 4-[ethyl(dimethyl)ammonio]butanoate (methyl-GBB) protects brain mitochondrial function and improves neurological outcomes after transient middle cerebral artery occlusion (MCAO). The effects of 14 days of pretreatment with methyl-GBB (5 mg/kg, p.o.) on brain acylcarnitine (short-, long- and medium-chain) concentrations and brain mitochondrial function were evaluated in Wistar rats. Additionally, the mitochondrial respiration and reactive oxygen species (ROS) production rates were determined using ex vivo high-resolution fluorespirometry under normal conditions, in models of ischemia-reperfusion injury (reverse electron transfer and anoxia-reoxygenation) and 24 h after MCAO. MCAO model rats underwent vibrissae-evoked forelimb-placing and limb-placing tests to assess neurological function. The infarct volume was measured on day 7 after MCAO using 2,3,5-triphenyltetrazolium chloride (TTC) staining. Treatment with methyl-GBB significantly reduced the LCAC content in brain tissue, which decreased the ROS production rate without affecting the respiration rate, indicating an increase in mitochondrial coupling. Furthermore, methyl-GBB treatment protected brain mitochondria against anoxia-reoxygenation injury. In addition, treatment with methyl-GBB significantly reduced the infarct size and improved neurological outcomes after MCAO. Increased mitochondrial coupling efficiency may be the basis for the neuroprotective effects of methyl-GBB. This study provides evidence that maintaining brain energy metabolism by lowering the levels of LCACs protects against ischemia-induced brain damage in experimental stroke models.
Topics: Rats; Animals; Rats, Wistar; Reactive Oxygen Species; Mitochondria; Brain; Brain Ischemia; Infarction, Middle Cerebral Artery; Neuroprotective Agents; Hypoxia; Reperfusion Injury
PubMed: 37924790
DOI: 10.1016/j.biopha.2023.115803 -
Respiratory Research Oct 2023The standard therapy for bronchial asthma consists of combinations of acute (short-acting ß-sympathomimetics) and, depending on the severity of disease, additional...
INTRODUCTION
The standard therapy for bronchial asthma consists of combinations of acute (short-acting ß-sympathomimetics) and, depending on the severity of disease, additional long-term treatment (including inhaled glucocorticoids, long-acting ß-sympathomimetics, anticholinergics, anti-IL-4R antibodies). The antidepressant amitriptyline has been identified as a relevant down-regulator of immunological T2-phenotype in asthma, acting-at least partially-through inhibition of acid sphingomyelinase (ASM), an enzyme involved in sphingolipid metabolism. Here, we investigated the non-immunological role of amitriptyline on acute bronchoconstriction, a main feature of airway hyperresponsiveness in asthmatic disease.
METHODS
After stimulation of precision cut lung slices (PCLS) from mice (wildtype and ASM-knockout), rats, guinea pigs and human lungs with mediators of bronchoconstriction (endogenous and exogenous acetylcholine, methacholine, serotonin, endothelin, histamine, thromboxane-receptor agonist U46619 and leukotriene LTD4, airway area was monitored in the absence of or with rising concentrations of amitriptyline. Airway dilatation was also investigated in rat PCLS by prior contraction induced by methacholine. As bronchodilators for maximal relaxation, we used IBMX (PDE inhibitor) and salbutamol (ß-adrenergic agonist) and compared these effects with the impact of amitriptyline treatment. Isolated perfused lungs (IPL) of wildtype mice were treated with amitriptyline, administered via the vascular system (perfusate) or intratracheally as an inhalation. To this end, amitriptyline was nebulized via pariboy in-vivo and mice were ventilated with the flexiVent setup immediately after inhalation of amitriptyline with monitoring of lung function.
RESULTS
Our results show amitriptyline to be a potential inhibitor of bronchoconstriction, induced by exogenous or endogenous (EFS) acetylcholine, serotonin and histamine, in PCLS from various species. The effects of endothelin, thromboxane and leukotrienes could not be blocked. In acute bronchoconstriction, amitriptyline seems to act ASM-independent, because ASM-deficiency (Smdp1) did not change the effect of acetylcholine on airway contraction. Systemic as well as inhaled amitriptyline ameliorated the resistance of IPL after acetylcholine provocation. With the flexiVent setup, we demonstrated that the acetylcholine-induced rise in central and tissue resistance was much more marked in untreated animals than in amitriptyline-treated ones. Additionally, we provide clear evidence that amitriptyline dilatates pre-contracted airways as effectively as a combination of typical bronchodilators such as IBMX and salbutamol.
CONCLUSION
Amitriptyline is a drug of high potential, which inhibits acute bronchoconstriction and induces bronchodilatation in pre-contracted airways. It could be one of the first therapeutic agents in asthmatic disease to have powerful effects on the T2-allergic phenotype and on acute airway hyperresponsiveness with bronchoconstriction, especially when inhaled.
Topics: Mice; Rats; Humans; Animals; Guinea Pigs; Bronchoconstriction; Methacholine Chloride; Amitriptyline; Histamine; Bronchodilator Agents; Serotonin; Acetylcholine; Sympathomimetics; 1-Methyl-3-isobutylxanthine; Dilatation; Lung; Asthma; Albuterol; Endothelins; Thromboxanes
PubMed: 37907918
DOI: 10.1186/s12931-023-02580-6 -
Frontiers in Bioscience (Landmark... Aug 2023A previously unstudied medicinal plant, (Berland.) I.M. Johnst. (Scrophulariaceae) was investigated to evaluate its potential in preventing and treating...
Neuroprotection against Aluminum Chloride-Induced Hippocampus Damage in Albino Wistar Rats by (Berl.) I.M. Johnst. Leaf Extracts: A Detailed Insight into Phytochemical Analysis and Antioxidant and Enzyme Inhibition Assays.
BACKGROUND
A previously unstudied medicinal plant, (Berland.) I.M. Johnst. (Scrophulariaceae) was investigated to evaluate its potential in preventing and treating neurodegenerative diseases, including Alzheimer's disease.
METHODS
Methanolic leaf extract (MELE) and its fractions (HELE, CHLE, and BULE) were evaluated for their polyphenolic content and antioxidant activity by five different methods, including enzyme inhibition assays, which are clinically linked to neurodegenerative diseases. The potentially active -butanol fraction (BULE) was further evaluated for its neuroprotective effects using an albino rat animal model and phytoconstituents profiling using Liquid chromatography with tandem mass spectrometry (LC-MS/MS), and molecular docking by Maestro® Schrödinger.
RESULTS
The -butanol fraction (BULE) in the hydroalcoholic leaf extract exhibited the highest total phenolic content (230.435 ± 1.575 mg gallic acid equivalent gm-1± SD). The chloroform leaf extract exhibited the highest total flavonoid content (293.343 ± 3.756 mg quercetin equivalent gm-1± SD) as well as the highest antioxidant content, which was equivalent to Trolox, with five assay methods. Similarly, the chloroform and n-butanol fractions from the hydroalcoholic leaf extract significantly inhibited human acetylcholinesterase and butyrylcholinesterase with their IC50 values of 12.14 ± 0.85 and 129.73 ± 1.14 µg∙mL-1, respectively. The study revealed that BULE exhibited a significant neuroprotective effect at doses of 200 and 400 mg/kg/day in an aluminum chloride-induced neurodegenerative albino rat model. The LC-MS/MS analysis of BULE tentatively confirmed the presence of biologically active secondary metabolites, such as theobromine, propyl gallate, quercetin-3-O-glucoside, myricetin-3-acetylrhamnoside, isoquercitrin-6'-O-malonate, diosmetin-7-O-glucuronide-3'-O-pentose, pinoresinol diglucoside, asarinin, eridictoyl, epigallocatechin, methyl gallate derivative, and eudesmin. The results from the computational molecular docking of the identified secondary metabolites revealed that diosmetin-7-O-glucuronide-3'-O-pentose had the highest binding affinity to human butyrylcholinesterase, while isoquercetin-6'-O-malonate had the highest to human acetylcholinesterase, and pinoresinol diglucoside to human salivary alpha-amylase.
CONCLUSIONS
The present study concluded a need for further exploration into this medicinal plant, including the isolation of the bioactive compounds responsible for its neuroprotective effects.
Topics: Rats; Animals; Humans; Antioxidants; Neuroprotection; Neuroprotective Agents; Acetylcholinesterase; Aluminum Chloride; Butyrylcholinesterase; 1-Butanol; Chloroform; Chromatography, Liquid; Glucuronides; Molecular Docking Simulation; Tandem Mass Spectrometry; Hippocampus; Scrophulariaceae; Plant Extracts
PubMed: 37664939
DOI: 10.31083/j.fbl2808184 -
Journal of Hazardous Materials Oct 2023Bisulfite-activated permanganate (S(IV)/Mn(VII)) process has proven to be a promising method for rapidly degrading micropollutants. Previous studies have shown that the...
Bisulfite-activated permanganate (S(IV)/Mn(VII)) process has proven to be a promising method for rapidly degrading micropollutants. Previous studies have shown that the treatment efficiency of the S(IV)/Mn(VII) process suffer from significant water matrix effects while the mechanism still remains unclear. This study systematically investigates the influence of chloride, which is a common water constituent, on the S(IV)/Mn(VII) process. Addition of chloride decreased the removal of methyl phenyl sulfoxide, phenol, benzoic acid and carbamazepine by the S(IV)/Mn(VII) process but increased dimethoxybenzene removal. The distribution of reactive species in the S(IV)/Mn(VII) process in the absence and presence of chloride was determined with relative rate method. The S(IV)/Mn(VII) process primarily relies on SO and reactive manganese species (RMnS) for pollutant abatement while dosing chloride decreased the concentration of these reactive species. Reactive chlorine species (RCS), such as Cl and ClO, are formed through the reaction of SO with chloride, and become more important at high concentrations of chloride. RMnS includes Mn(VI), Mn(V) and Mn(III), but none of these species are capable of oxidizing chloride. However, chloride retarded the consumption of bisulfite which reduced RMnS and RCS in turn. DOM inhibited pollutant removal by the S(IV)/Mn(VII) process while the impact mechanism was significantly altered by chloride. Additionally, the study observed a synergistic inhibition of DOM and chloride on the degradation of pollutants that are highly reactive towards Cl and ClO.
PubMed: 37531765
DOI: 10.1016/j.jhazmat.2023.132173 -
Environmental Science & Technology Dec 2023Methyl halides play important roles in stratospheric ozone depletion, but their formation mechanisms are not well defined. This study demonstrated that iron-based...
Methyl halides play important roles in stratospheric ozone depletion, but their formation mechanisms are not well defined. This study demonstrated that iron-based photochemistry significantly enhanced alkyl halide production by promoting the reaction of the representative monomer of lignin with halide ions in saline water under solar light irradiation. The methyl chloride (CHCl) emission from the light/Fe(III) process was 2 orders of magnitude higher than dark treatment and in the absence of iron. In addition, bromide and iodide showed better reactivity in the formation of the corresponding methyl bromide (CHBr) and methyl iodide (CHI). Alkyl halides identified from seawater, brackish water, and salt pan water under sunlight irradiation were positively correlated with the Fe(III) concentrations, indicating that iron-based photochemistry is ubiquitous. This work suggested that the photoinduced formation of methyl radical and redox cycling of iron triggered by the Fenton-like reaction are responsible for the enhanced release of alkyl halides. This study represents an abiotic formation pathway of alkyl halides, which accounts for a portion of the unidentified sources of halocarbons in the ocean.
Topics: Iron; Photochemistry; Hydrocarbons, Halogenated; Seawater; Ferric Compounds
PubMed: 38010203
DOI: 10.1021/acs.est.3c05552 -
Iranian Journal of Public Health Mar 2024Multiple Myeloma (MM) is a neoplastic hematologic disorder caused by the excessive proliferation of plasma cells and leads to bone lesions, anemia, and kidney failure.... (Review)
Review
Multiple Myeloma (MM) is a neoplastic hematologic disorder caused by the excessive proliferation of plasma cells and leads to bone lesions, anemia, and kidney failure. No definite etiology has been proposed for MM, but several environmental and genetic risk factors have been implicated so far. Exposure to pesticides, benzene, and organic solvents like methyl chloride have been considered a potential risk factor. Asbestos, ionizing radiation, and wood dust exposure have also been associated with MM. As MM is a relatively rare condition, the number of studies is insufficient, and in many studies, only a few study participants recall exposure to any agents. Therefore, establishing a definite risk factor is cumbersome and further studies with large study samples are needed. By recognizing these occupational risk factors, clinicians can encourage employees to reduce their exposure as more as possible and implement precautionary measures. In this review, we highlighted the current research on the potential association between occupational exposures and MM. Because of these studies, new regulations with the goal of occupational exposure reduction are anticipated in the future.
PubMed: 38919290
DOI: 10.18502/ijph.v53i3.15137 -
ACS Omega Sep 2023Methylene blue (MB) dye or methyl thioninium chloride is one of the hazardous cationic dyes that are discharged into the textile effluent causing a highly negative...
Methylene blue (MB) dye or methyl thioninium chloride is one of the hazardous cationic dyes that are discharged into the textile effluent causing a highly negative environmental impact. The present work targets the investigation of the adsorption performance of some chitosan-modified products toward the MB dye from simulated solutions. The claimed chitosan derivatives were prepared, characterized, and applied for the removal of lead and copper cations from an aqueous medium in a previous work. These include: ,-carboxymethyl chitosan (,-CM/Cs), chitosan grafted with glutaraldehyde (Cs/GA), chitosan cross-linked with GA/epichlorohydrin (Cs/GA/ECH), and chitosan cross-linked with glutaraldehyde/methylene bis(acrylamide) (Cs/GA/MBA). The modified chitosan derivatives in this study displayed outstanding mechanical qualities, exceptional reusability, and a significant amount of adsorption capacity. The ability of prepared Cs derivatives to eradicate MB was as follows: ,-CM/Cs (95.1 mg/g) < Cs/GA (120.1 mg/g) < Cs/GA/ECH (220.1 mg/g) < Cs/GA/MBA (270.0 mg/g). The swelling performance of the prepared sorbents was verified under different experimental conditions, and the data revealed that the maximum swelling was attained at pH = 9, temperature 55 °C, and after 24 h. The produced Cs derivatives showed exceptional reusability by maintaining higher adsorption effectiveness throughout five cycles. The MB dye was adsorbed onto the modified derivatives according to pseudo-second-order kinetics and the Langmuir model. Moreover, the adsorption process was monitored via atomic force microscopy to verify the differences between the dye-free and dye-loaded adsorbents.
PubMed: 37744862
DOI: 10.1021/acsomega.3c03735 -
Acta Crystallographica. Section E,... Sep 2023In the hydrated title salt, CHNS ·Cl·HO, the asymmetric unit comprises one 2-amino-5-{(1)-1-[(carbamo-thioyl-amino)-imino]-eth-yl}-4-methyl-1,3-thia-zol-3-ium cation,...
In the hydrated title salt, CHNS ·Cl·HO, the asymmetric unit comprises one 2-amino-5-{(1)-1-[(carbamo-thioyl-amino)-imino]-eth-yl}-4-methyl-1,3-thia-zol-3-ium cation, one chloride anion and one water mol-ecule of crystallization. The cation is nearly flat (r.m.s. deviation of non-H atoms is 0.0814 Å), with the largest deviation of 0.1484 (14) Å observed for one of the methyl C atoms. In the crystal, the cations are linked by O-H⋯Cl, N-H⋯Cl, N-H⋯O, N-H⋯S and C-H⋯S hydrogen bonds, forming a tri-periodic network. The most important contributions to the crystal packing are from H⋯H (35.4%), S⋯H/H⋯S (24.4%), N⋯H/H⋯N (8.7%), Cl⋯H/H⋯Cl (8.2%) and C⋯H/H⋯C (7.7%) inter-actions.
PubMed: 37693676
DOI: 10.1107/S2056989023007090 -
ACS Applied Materials & Interfaces Nov 2023Sustainable energy conversion and effective biosynthesis for value-added chemicals have attracted considerable attention, but most biosynthesis systems cannot work... (Review)
Review
Sustainable energy conversion and effective biosynthesis for value-added chemicals have attracted considerable attention, but most biosynthesis systems cannot work independently without external power. In this work, a self-powered biohybrid system based on organic materials is designed and constructed successfully by integrating electroactive microorganisms with electrochemical devices. Among them, the hybrid living materials based on /poly[3-(3'-N,N,N-triethylamino-1'-propyloxy)-4-methyl-2,5-thiophene chloride] (PMNT) biofilms for microbial fuel cells played a crucial role in electrocatalytic biocurrent generation by using biowaste as the only energy source. Without any external power supplies, the self-powered biohybrid systems could generate, convert, and store electrical energy for effective photosynthetic regulation and sustained chemical production. This work provides a new strategy to combine comprehensive renewable energy production with chemical manufacturing without an external power source in the future.
PubMed: 37924284
DOI: 10.1021/acsami.3c12400 -
Langmuir : the ACS Journal of Surfaces... Nov 2023DNA nanotechnology is the future of many products in the pharmaceutical and cosmetic industries. Self-assembly of this negatively charged biopolymer at surfaces and...
DNA nanotechnology is the future of many products in the pharmaceutical and cosmetic industries. Self-assembly of this negatively charged biopolymer at surfaces and interfaces is an essential step to elaborate its field of applications. In this study, the ionic liquid (IL) monolayer-assisted self-assembly of DNA macromolecules at the air-water interface has been closely monitored by employing various quantitative techniques, namely, surface pressure-area (π-) isotherms, surface potential, interfacial rheology, and X-ray reflectivity (XRR). The π- isotherms reveal that the IL 1,3-didecyl 3-methyl imidazolium chloride induces DNA self-assembly at the interface, leading to a thick viscoelastic film. The interfacial rheology exhibits a notable rise in the viscoelastic modulus as the surface pressure increases. The values of storage and loss moduli measured as a function of strain frequency suggest a relaxation frequency that depends on the length of the macromolecule. The XRR measurements indicate a considerable increase in DNA layer thickness at the elevated surface pressures depending on the number of base pairs of the DNA. The results are considered in terms of the electrostatic and hydrophobic interactions, allowing a quantitative conclusion about the arrangement of DNA strands underneath the monolayer of the ILs at the air-water interface.
Topics: Ionic Liquids; Surface Properties; Water; DNA; Pressure
PubMed: 37922422
DOI: 10.1021/acs.langmuir.3c02212