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1.
J Biochem Mol Toxicol ; 38(1): e23531, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37724821

RESUMO

Myocardial infarction (MI) is a common type of ischemic heart disease that affects millions of people worldwide. In recent times, nanotechnology has become a very promising field with immense applications. The current exploration was conducted to synthesize the chitosan-sodium alginate-polyethylene glycol-Ally isothiocyanate nanocomposites (CSP-AIso-NCs) and evaluate their beneficial roles against the isoproterenol (ISO)-induced MI in rats. The CSP-AIso-NCs were prepared and characterized by several characterization techniques. The MI was initiated in the rats by the administration of 85 mg/kg of ISO for 2 days and treated with 10 and 20 mg/kg of CSP-AIso-NCs for 1 month. The changes in heart weight and bodyweight were measured. The cardiac function markers were assessed with echocardiography. The lipid profiles, Na+, K+, and Ca2+ ions, cardiac biomarkers, antioxidant parameters, and inflammatory cytokines were assessed using corresponding assay kits. The histopathological study was done on the heart tissues. The UV spectral analysis revealed the maximum peak at 208 nm, which confirms the formation of CSP-AIso-NCs. The FT-IR analysis revealed the occurrence of different functional groups, and the crystallinity of the CSP-AIso-NCs was proved by the XRD analysis. DLS analysis indicated the size of the CSP-AIso-NCs at 146.50 nm. The CSP-AIso-NCs treatment increased the bodyweight and decreased the HW/BW ratio in the MI rats. The status of lipids was reduced, and HDL was elevated in the CSP-AIso-NCs administered to MI rats. CSP-AIso-NCs decreased the LVEDs, LVEDd, and NT-proBNP and increased the LVEF level. The oxidative stress markers were decreased, and the antioxidants were increased by the CSP-AIso-NCs treatment in the MI rats. The Na+ and Ca+ ions were reduced, and the K+ ions were increased by the CSP-AIso-NCs. The interleukin-1ß and tumor necrosis factor-α were also depleted, and Nrf-2 was improved in the CSP-AIso-NCs administered to MI rats. The histological study revealed the ameliorative effects of CSP-AIso-NCs. Overall, our outcomes revealed that the CSP-AIso-NCs are effective against the ISO-induced MI rats. Hence, it could be a hopeful therapeutic nanomedicine for MI treatment.


Assuntos
Quitosana , Infarto do Miocárdio , Humanos , Ratos , Animais , Isoproterenol/toxicidade , Quitosana/farmacologia , Alginatos/farmacologia , Alginatos/metabolismo , Alginatos/uso terapêutico , Polietilenoglicóis/farmacologia , Espectroscopia de Infravermelho com Transformada de Fourier , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/patologia , Antioxidantes/metabolismo , Estresse Oxidativo , Íons/metabolismo , Íons/farmacologia , Íons/uso terapêutico , Miocárdio/metabolismo
2.
J Appl Toxicol ; 44(4): 553-563, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37950502

RESUMO

Neurotoxicity induced by psychoactive substances is often accompanied by an imbalance of intracellular calcium ions. It is unclear whether calcium ions play a role in the toxicity induced by psychoactive substances. In the present study, we aimed to evaluate the occurrence of calcium dysregulation and its contribution to cytotoxicity in human neurotypic SH-SY5Y cells challenged with a recently developed psychoactive substance 4-methylethcathinone (4-MEC). An increase in the intracellular calcium was detected by inductively coupled plasma atomic emission spectrometry and Fluo-3 AM dye in SH-SY5Y cells after being treated with 4-MEC. The increase of intracellular Ca2+ level mediated G0/G1 cell cycle arrest and ROS/endoplasmic reticulum stress-autophagy signaling pathways to achieve the toxicity of 4-MEC. In particular, N-acetyl-L-cysteine, a classical antioxidant, was found to be a potential treatment for 4-MEC-induced toxicity. Taken together, our results demonstrate that an increase in intracellular calcium content is one of the mechanisms of 4-MEC-induced toxicity. This study provides a molecular basis for the toxicity mechanism and therapeutic intervention of psychoactive substances.


Assuntos
Anfetaminas , Cálcio , Neuroblastoma , Propiofenonas , Humanos , Cálcio/metabolismo , Linhagem Celular Tumoral , Íons/farmacologia , Apoptose
3.
J Dairy Sci ; 107(2): 1211-1227, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37730173

RESUMO

The objective of this experiment was to examine the effects of supplementation and dose of rumen-protected choline (RPC) on markers of inflammation and metabolism in liver and mammary tissue during an intramammary lipopolysaccharide (LPS) challenge. Parous Holstein cows were blocked by calving month and randomly assigned within block to receive 45 g/d of RPC (20.4 g/d of choline ions; CHOL45), 30 g/d of RPC (13.6 g/d of choline ions; CHOL30), or no RPC (CON) as a top-dress starting 24 d before expected calving until 21 d postpartum. Cows were alternately assigned within treatment group to either receive an intramammary LPS challenge (200 µg in each rear quarter; Escherichia coli O111:B4) or not at 17 DIM (CHOL45, n = 9; CHOL45-LPS, n = 9; CHOL30, n = 11; CHOL30-LPS, n = 10; CON, n = 10; CON-LPS, n = 9). Hepatic and mammary tissues were collected from all cows on d 17 postpartum. Hepatic and mammary tissues were collected at ∼7.5 and 8 h, respectively, after the LPS challenge. An additional mammary biopsy was conducted on LPS-challenged cows (CHOL45-LPS, CHOL30-LPS, and CON-LPS) at 48 h postchallenge. Hepatic and mammary RNA copy numbers were quantified for genes involved in apoptosis, methylation, inflammation, oxidative stress, and mitochondrial function using NanoString technology. Targeted metabolomics was conducted only on mammary tissue samples (both 8 and 48 h biopsies) to quantify 143 metabolites including choline metabolites, amino acids, biogenic amines and derivatives, organic acids, carnitines, and glucose. Hepatic IFNG was greater in CHOL45 as compared with CON in unchallenged cows, suggesting an improvement in type 1 immune responses. Hepatic CASP3 was greater in CHOL45-LPS as compared with CON-LPS, suggesting greater apoptosis. Mammary IL6 was reduced in CHOL30-LPS cows as compared with CHOL45-LPS and CON-LPS (8 and 48 h). Mammary GPX4 and COX5A were reduced in CHOL30-LPS as compared with CON-LPS (8 h), and SDHA was reduced in CHOL30-LPS as compared with CON-LPS (8 and 48 h). Both CHOL30-LPS and CHOL45-LPS cows had lesser mammary ATP5J than CON-LPS, suggesting that dietary RPC supplementation altered mitochondrial function following LPS challenge. Treatment did not affect mammary concentrations of any metabolite in unchallenged cows, and only 4 metabolites were affected by dietary RPC supplementation in LPS-challenged cows. Mammary concentrations of isobutyric acid and 2 acyl-carnitines (C4:1 and C10:2) were reduced in CHOL45-LPS as compared with CHOL30-LPS and CON-LPS. Taken together, reductions in medium- and short-chain carnitines along with an increase in long-chain carnitines in mammary tissue from CHOL45-LPS cows suggests less fatty acid entry into the ß oxidation pathway. Although the intramammary LPS challenge profoundly affected markers for inflammation and metabolism in liver and mammary tissue, dietary RPC supplementation had minimal effects on inflammatory markers and the mammary metabolome.


Assuntos
Doenças dos Bovinos , Lipopolissacarídeos , Feminino , Bovinos , Animais , Lipopolissacarídeos/farmacologia , Colina/metabolismo , Suplementos Nutricionais , Lactação , Rúmen/metabolismo , Leite/química , Dieta/veterinária , Fígado/metabolismo , Inflamação/veterinária , Inflamação/metabolismo , Íons/análise , Íons/metabolismo , Íons/farmacologia , Doenças dos Bovinos/metabolismo
4.
Ecotoxicol Environ Saf ; 271: 116013, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38281433

RESUMO

The damage excessive neodymium (Nd) causes to animals and plants should not be underestimated. However, there is little research on the impact of pH and associated ions on the toxicity of Nd. Here, a biotic ligand model (BLM) was expanded to predict the effects of pH and chief anions on the toxic impact of Nd on wheat root elongation in a simulated soil solution. The results suggested that Nd3+ and NdOH2+ were the major ions causing phytotoxicity to wheat roots at pH values of 4.5-7.0. The Nd toxicity decreased as the activities of H+, Ca2+, and Mg2+ increased but not when the activities of K+ and Na+ increased. The results indicated that H+, Ca2+, and Mg2+ competed with Nd for binding sites. An extended BLM was developed to consider the effects of pH, H+, Ca2+, and Mg2+, and the following stability constants were obtained: logKNdBL = 2.51, logKNdOHBL = 3.90, logKHBL = 4.01, logKCaBL = 2.43, and logKMgBL = 2.70. The results demonstrated that the BLM could predict the Nd toxicity well while considering the competition of H+, Ca2+, Mg2+ and the toxic species Nd3+ and NdOH2+ for binding sites.


Assuntos
Neodímio , Poluentes do Solo , Neodímio/toxicidade , Triticum , Ligantes , Poluentes do Solo/toxicidade , Modelos Biológicos , Raízes de Plantas , Íons/farmacologia , Concentração de Íons de Hidrogênio
5.
J Cell Physiol ; 238(8): 1836-1849, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37334439

RESUMO

Quiescent cancer cells are major impediments to effective radiotherapy (RT) and exhibit limited sensitivity to traditional photon therapy. Herein, the functional role and underlying mechanism of carbon ions in overcoming the radioresistance of quiescent cervical cancer HeLa cells were determined. Briefly, serum withdrawal was used to induce synchronized quiescence in HeLa cells. Quiescent HeLa cells displayed strong radioresistance and DNA repair potential. After irradiation with carbon ions, the DNA damage repair pathway may markedly rely on error-prone nonhomologous end-joining in proliferating cells, whereas the high-precision homologous recombination pathway is more relevant in quiescent cells. This phenomenon could be explained by the ionizing radiation (IR)-induced cell cycle re-entry of quiescent cancer cells. There are three strategies for eradicating quiescent cancer cells using high-linear energy transfer (LET) carbon ions: direct cell death through complex DNA damage; apoptosis via an enhanced mitochondria-mediated intrinsic pathway; forced re-entry of quiescent cancer cells into the cell cycle, thereby improving their susceptibility to IR. Silencing ß-catenin signaling is essential for maintaining the dormant state in quiescent cells. Herein, carbon ions activated the ß-catenin pathway in quiescent cells, and inhibition of this pathway improved the resistance of quiescent HeLa cells to carbon ions by alleviating DNA damage, improving DNA damage repair, maintaining quiescent depth, and inhibiting apoptosis. Collectively, carbon ions conquer the radioresistance of quiescent HeLa cells by activating ß-catenin signaling, which provides a theoretical basis for improved therapeutic effects in patients with middle-advanced-stage cervical cancer with radioresistance.


Assuntos
Neoplasias do Colo do Útero , beta Catenina , Feminino , Humanos , Células HeLa , beta Catenina/genética , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/radioterapia , Reparo do DNA , Carbono , Íons/farmacologia , Dano ao DNA , Tolerância a Radiação/genética
6.
Mar Drugs ; 21(12)2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38132946

RESUMO

Alginate-based materials have gained significant attention in the medical industry due to their biochemical properties. In this article, we aimed to synthesize Cotton-Alginate-Copper Composite Materials (COT-Alg(-)Cu(2+)). The main purpose of this study was to assess the biochemical properties of new composites in the area of blood plasma coagulation processes, including activated partial thromboplastin time (aPTT), prothrombin time (PT), and thrombin time (TT). This study also involved in vitro antimicrobial activity evaluation of materials against representative colonies of Gram-positive and Gram-negative bacteria and antifungal susceptibility tests. The materials were prepared by immersing cotton fibers in an aqueous solution of sodium alginate, followed by ionic cross-linking of alginate chains within the fibers with Cu(II) ions to yield antimicrobial activity. The results showed that the obtained cotton-alginate-copper composites were promising materials to be used in biomedical applications, e.g., wound dressing.


Assuntos
Alginatos , Cobre , Cobre/química , Alginatos/química , Antibacterianos/farmacologia , Antibacterianos/química , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Coagulação Sanguínea , Tempo de Protrombina , Tempo de Tromboplastina Parcial , Íons/farmacologia
7.
J Dairy Sci ; 106(12): 8561-8582, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37500444

RESUMO

Recent studies have suggested that dietary rumen-protected choline (RPC) supplementation can modulate immune function, attenuate inflammation, and improve performance in periparturient dairy cattle; however, this has yet to be evaluated during a mastitis challenge. Therefore, the objective of this study was to examine the effects of supplementation and dose of RPC on metabolism, inflammation, and performance during an intramammary lipopolysaccharide (LPS) challenge. Parous Holstein cows (parity, mean ± SD, 1.9 ± 1.1 at enrollment) were blocked by calving month and randomly assigned within block to receive either 45 g/d of RPC (20.4 g/d of choline ions; CHOL45, n = 18), 30 g/d of RPC (13.6 g/d of choline ions; CHOL30, n = 21), or no RPC (CON, n = 19) as a top-dress starting 24 d before expected calving until 21 d postpartum. Cows were alternately assigned within treatment group to either receive an intramammary LPS challenge (200 µg in each rear quarter; Escherichia coli O111:B4) or not at 17 DIM. Before the challenge, CHOL45 and CHOL30 cows produced 3.4 and 3.8 (±1.2 SED) kg/d more milk than CON, respectively. Dietary RPC supplementation did not mitigate the milk loss associated with the intramammary LPS challenge; however, CHOL45 and CHOL30 cows produced 3.1 and 3.5 (±1.4 SED) kg/d more milk than CON, respectively in the carryover period (22 to 84 DIM). Dietary RPC supplementation enhanced plasma ß-hydroxybutyrate (BHB) concentrations before the LPS challenge, and increased plasma nonesterified fatty acids (NEFA) and acetylcarnitine concentrations during the LPS challenge, potentially reflecting greater adipose tissue mobilization, fatty acid transport and oxidation. Aside from trimethylamine N-oxide and sarcosine, which were increased in CHOL45-LPS as compared with CON-LPS, most other choline metabolite concentrations in plasma were unaffected by treatment, likely because more choline was being secreted in milk. Plasma lactic acid concentrations were decreased in CHOL45-LPS and CHOL30-LPS as compared with CON-LPS, suggesting a reduction in glycolysis or an enhancement in the flux through the lactic acid cycle to support gluconeogenesis. Plasma concentrations of fumaric acid, a byproduct of AA catabolism and the urea cycle, were increased in both choline groups as compared with CON-LPS during the LPS challenge. Cows in the CHOL45 group had greater plasma antioxidant potential before the LPS challenge and reduced plasma methionine sulfoxide concentrations during the LPS challenge compared with CON-LPS, suggesting an improvement in oxidant status. Nevertheless, concentrations of inflammatory markers such as haptoglobin and tumor necrosis factor α (TNFα) were not affected by treatment. Taken together, our data suggest that the effects of dietary RPC supplementation on milk yield could be mediated through metabolic pathways and are unlikely to be related to the resolution of inflammation in periparturient dairy cattle. Lastly, dose responses to dietary RPC supplementation were not found for various economically important outcomes including milk yield, limiting the justification for feeding a greater dietary RPC dose in industry.


Assuntos
Doenças dos Bovinos , Lipopolissacarídeos , Gravidez , Feminino , Bovinos , Animais , Lipopolissacarídeos/farmacologia , Colina/farmacologia , Colina/metabolismo , Suplementos Nutricionais , Lactação/fisiologia , Rúmen/metabolismo , Dieta/veterinária , Leite/metabolismo , Inflamação/veterinária , Inflamação/metabolismo , Ácido Láctico/metabolismo , Íons/metabolismo , Íons/farmacologia , Doenças dos Bovinos/metabolismo
8.
Int J Phytoremediation ; 25(7): 889-899, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36062912

RESUMO

In the present study, we used exogenous naringenin (0.5 mM) pretreatment before the stress (25 mM NaCl) on the growth and tolerance of safflower seedlings under non-salinity conditions and salinity conditions. Our results showed that salinity treatment significantly declined the biomass, leaf relative water content, chlorophyll content, K+ content, and K+/Na+ ratio by 28%, 28%, 12%, 36%, and 56%, respectively, as compared to untreated control. The results obtained in the present study showed the beneficial effects of the pretreatment of naringenin in safflower seedlings under non-salinity conditions concerning increasing plant biomass, total phenolic compound, radical scavenging activity (RSA), soluble sugar content, proline, glutathione, enzymatic antioxidants, and K+ content. Nevertheless, naringenin pretreated plants showed a clear increment in the values of biomass, RSA, total phenolic compound, and catalase enzyme activity parameters under salinity stress. Salinity stress caused ionic phytotoxicity and oxidative stress by enhancing Na+ content, H2O2 accumulation, malondialdehyde (MDA), and antioxidants. However, naringenin alleviated salt-induced oxidative stress by decreasing H2O2 and MDA content in the leaves and improving the catalase activity in treated plants. Generally, it could be concluded pretreatment of naringenin before stress could partly diminish NaCl-caused oxidative stress in safflower seedlings, probably due to improvement in enzymatic and non-enzymatic antioxidants and reduced cell membrane damage.


We report for the first time that applying exogenous naringenin pretreatment before the stress could improve growth and diminish NaCl-caused oxidative stress in safflower seedlings, probably due to the improvement in enzymatic and non-enzymatic antioxidants and reduced cell membrane damage. This implies that applying exogenous naringenin pretreatment before the stress is a promising approach for sustainable crop production under salinity stress.


Assuntos
Carthamus tinctorius , Cloreto de Sódio , Cloreto de Sódio/metabolismo , Cloreto de Sódio/farmacologia , Plântula , Catalase/metabolismo , Catalase/farmacologia , Carthamus tinctorius/metabolismo , Peróxido de Hidrogênio/metabolismo , Peróxido de Hidrogênio/farmacologia , Biodegradação Ambiental , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Sódio , Íons/metabolismo , Íons/farmacologia
9.
Drug Dev Res ; 84(2): 312-325, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36658741

RESUMO

Copper ions play a crucial role in the progression of cancers. Tumor tissue is rich in copper ions, and copper chelators could potentially scavenge these copper ions and thus exert an antitumor effect. In this study, we report the synthesis of a novel thieno[3,2-c]pyridine compound we have called "JYFY-001" that can act as the copper chelator thanks to the inclusion of an N-(pyridin-2-yl)acetamide moiety that targets copper ions. JYFY-001 potently inhibited cancer proliferation, inducing cell apoptosis and impairing the extracellular acidification rate and oxygen consumption rate of colorectal cancer (CRC) cells. JYFY-001 also inhibited the growth of a CRC-transplanted tumor in a dose-dependent manner, inducing apoptosis of the tumor cells and promoting the infiltration of lymphocytes in the CRC-transplanted tumor tissues. JYFY-001 also enhanced the antitumor effects of the programmed cell death protein 1 (PD-1) inhibitor. The relatively benign nature of JYFY-001 was demonstrated by the effect on normal cell viability and acute toxicity tests in mice. Our findings suggest that JYFY-001 is a prospective copper chelator to be used as a targeted drug and a synergist of immunotherapy for CRC treatments.


Assuntos
Neoplasias Colorretais , Cobre , Camundongos , Animais , Cobre/farmacologia , Cobre/uso terapêutico , Estudos Prospectivos , Apoptose , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Quelantes/farmacologia , Quelantes/uso terapêutico , Íons/farmacologia , Íons/uso terapêutico , Proliferação de Células , Linhagem Celular Tumoral
10.
Mol Biol (Mosk) ; 57(6): 1098-1129, 2023.
Artigo em Russo | MEDLINE | ID: mdl-38062964

RESUMO

Intracellular calcium signaling is involved in regulating the key functional mechanisms of the nervous system. The control of neuronal excitability and plasticity by calcium ions underlies the mechanisms of higher nervous activity, and the mechanisms of this control are of particular interest to researchers. A family of highly specialized neuronal proteins described in recent decades can translate the information contained in calcium signals into the regulation of channels, enzymes, receptors, and transcription factors. Neuronal calcium sensor-1 (NCS-1) is the most common member of the family, which is intensely expressed in central nervous system (CNS) cells; and controls several vital processes, such as neuronal growth and survival, reception, neurotransmission, and synaptic plasticity. In addition to calcium ions, NCS-1 can bind the so-called mobile, or signaling intracellular zinc, an increased concentration of which is a characteristic feature of cells in oxidative stress. Zinc coordination under these conditions stimulates NCS-1 oxidation to form a disulfide dimer (dNCS-1) with altered functional properties. A combined effect of mobile zinc and an increased redox potential of the medium can thus induce aberrant NCS-1 activity, including signals that promote survival of neuronal cells or induce their apoptosis and, consequently, the development of neurodegenerative processes. The review details the localization, expression regulation, structure, and molecular properties of NCS-1 and considers the current data on its signaling activity in health and disease, including zinc-dependent redox regulation cascades.


Assuntos
Sinalização do Cálcio , Proteínas Sensoras de Cálcio Neuronal , Oxirredução , Cálcio/metabolismo , Sinalização do Cálcio/fisiologia , Íons/metabolismo , Íons/farmacologia , Neurônios/metabolismo , Zinco/farmacologia , Proteínas Sensoras de Cálcio Neuronal/metabolismo
11.
Bull Exp Biol Med ; 176(1): 38-41, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38091135

RESUMO

Proton and ion radiation therapy, when used both as single radiation and in mixed radiation mode, have a number of advantages over the conventional γ-therapy that are determined by physical characteristics of accelerated particles. The paper presents the results of an in vitro study of the effectiveness of sequential exposures of Chinese hamster tumor cells B14-150 to proton (p) and 12C ion beams. We used 4 irradiation schemes differing by the sequence of exposure and the contribution of each radiation to the total dose. Synergism was shown for 12C ions dose contribution of 45% (taking into account the coefficient of relative biological efficiency) and the sequence 12C→p.


Assuntos
Prótons , Cricetinae , Animais , Cricetulus , Íons/farmacologia , Relação Dose-Resposta à Radiação
12.
Anal Biochem ; 643: 114527, 2022 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-34919899

RESUMO

Heavy metal detection is critical due to its harmful effects on human health and the ecosystem. Enzyme-based platforms attract attention for heavy metal detection such as silver, a toxic metal, due to being small, portable, and requiring only essential equipment compared with the basic analytical methods. In this study, magnetic cross-linked invertase aggregates (MCLIA) were developed for the first time as an enzyme-based signaling platform to detect Ag+ using a personal glucose meter (PGM). EDX, FTIR, and VSM results depicted that MCLIA was successfully developed and exhibits super-paramagnetism. In addition, MCLIA selectively detected the Ag+ at a sensitivity of 1.2 inhibition rate/µM in a linear range from 5 to 70 µM with a detection limit of 4.6 µM and IC50 value of 42.3 µM. These findings strongly indicate that MCLIA is applicable as a signal platform for portable quantification of other analytes that inhibits the invertase enzyme.


Assuntos
Técnicas Biossensoriais , Automonitorização da Glicemia , Prata/análise , Glucose Oxidase/antagonistas & inibidores , Glucose Oxidase/metabolismo , Íons/análise , Íons/metabolismo , Íons/farmacologia , Prata/metabolismo , Prata/farmacologia
13.
Eur Biophys J ; 51(3): 205-223, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35166865

RESUMO

Metal ion-membrane interactions have gained appreciable attention over the years resulting in increasing investigations into the mode of action of toxic and essential metals. More work has focused on essential ions like Ca or Mg and toxic metals like Cd and Pb, whereas this study investigates the effects of the abundant essential trace metal manganese with model lipid systems by screening zwitterionic and anionic glycerophospholipids. Despite its essentiality, deleterious impact towards cell survival is known under Mn stress. The fluorescent dyes Laurdan and diphenylhexatriene were used to assess changes in membrane fluidity both in the head group and hydrophobic core region of the membrane, respectively. Mn-rigidified membranes composed of the anionic phospholipids, phosphatidic acid, phosphatidylglycerol, cardiolipin, and phosphatidylserine. Strong binding resulted in large shifts of the phase transition temperature. The increase was in the order phosphatidylserine > phosphatidylglycerol > cardiolipin, and in all cases, saturated analogues > mono-unsaturated forms. Dynamic light scattering measurements revealed that Mn caused extensive aggregation of liposomes composed of saturated analogues of phosphatidic acid and phosphatidylserine, whilst the mono-unsaturated analogue had significant membrane swelling. Increased membrane rigidity may interfere with permeability of ions and small molecules, possibly disrupting cellular homeostasis. Moreover, liposome size changes could indicate fusion, which could also be detrimental to cellular transport. Overall, this study provided further understanding into the effects of Mn with biomembranes, whereby the altered membrane properties are consequential to the proper structural and signalling functions of membrane lipids.


Assuntos
Lipossomos , Manganês , Cardiolipinas/farmacologia , Íons/farmacologia , Lipossomos/química , Manganês/farmacologia , Fluidez de Membrana , Ácidos Fosfatídicos/química , Ácidos Fosfatídicos/farmacologia , Fosfatidilgliceróis/química , Fosfatidilserinas/farmacologia , Fosfolipídeos/química
14.
Inorg Chem ; 61(3): 1249-1253, 2022 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-34989562

RESUMO

Human carbonic anhydrase II (HCA) is a robust metalloprotein and an excellent biological model system to study the thermodynamics of metal ion coordination. Apo-HCA binds one zinc ion or two copper ions. We studied these binding processes at five temperatures (15-35 °C) using isothermal titration calorimetry, yielding thermodynamic parameters corrected for pH and buffer effects. We then sought to identify binding-induced structural changes. Our data suggest that binding at the active site organizes 6-8 residues; however, copper binding near the N-terminus results in a net unfolding of 6-7 residues. This surprising destabilization was confirmed using circular dichroism and protein stability measurements. Metal binding induced unfolding may represent an important regulatory mechanism, but it may be easily missed by NMR and X-ray crystallography. Thus, in addition to highlighting a highly novel binding-induced unfolding event, we demonstrate the value of calorimetry for studying the structural implications of metal binding.


Assuntos
Anidrase Carbônica II/antagonistas & inibidores , Inibidores da Anidrase Carbônica/farmacologia , Complexos de Coordenação/farmacologia , Cobre/farmacologia , Zinco/farmacologia , Sítios de Ligação/efeitos dos fármacos , Calorimetria , Anidrase Carbônica II/metabolismo , Inibidores da Anidrase Carbônica/química , Complexos de Coordenação/química , Cobre/química , Humanos , Íons/química , Íons/farmacologia , Desdobramento de Proteína , Zinco/química
15.
Environ Res ; 210: 112940, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35182597

RESUMO

Neuropsychological alterations have been identified in populations heavily exposed to metals with neurotoxic potential, such as manganese (Mn). This study examined the associations between Mn environmental exposure in school-aged children and executive functions, using structural equation modeling. Children, aged between 7 and 12 years (N = 181), were recruited from four elementary schools located in a region that is under the influence of atmospheric emissions from a ferro-manganese alloy plant in the municipality of Simões Filho, Bahia, Brazil. The following cognitive functions were evaluated: Intelligence, Inhibitory Control, Cognitive Flexibility, Verbal and Design Fluency, Verbal and Visual Working Memory and Attention. We performed structural equation modeling to identify the following executive functions latent variables: working memory, inhibitory control and cognitive flexibility. We further analyzed the relations between executive functions and Mn measured in hair (MnH) and toenails (MnTn) with linear mixed models, after controlling for co-variables. A positive effect at the individual level on working memory, inhibition control and cognitive flexibility was observed with MnTn after controlling for co-variables, but no association was found with MnH levels. However, children attending school most environmentally exposed to Mn emissions, which had the highest rate of Mn dust deposition, had the poorest scores on working memory. These findings suggest both benefits and risk of Mn on children's cognitive development.


Assuntos
Função Executiva , Manganês , Criança , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Humanos , Íons/análise , Íons/farmacologia , Manganês/análise , Manganês/toxicidade , Memória de Curto Prazo , Análise Multinível
16.
Mar Drugs ; 20(6)2022 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-35736204

RESUMO

The rapid preparation of safe and efficient wound dressings that meet the needs of the entire repair process remains a major challenge for effective therapeutic wound healing. Natural, sprayable Ion2+-COS/SA multifunctional dual-network gel films created by the in situ coordination of chitooligosaccharide (COS), metal ions and sodium alginate (SA) using casting and an in-situ spray method were synthesized. The gel films exhibited excellent physicochemical properties such as swelling, porosity and plasticity at a COS mass fraction of 3%. Furthermore, at this mass fraction, the addition of bimetallic ions led to the display of multifunctional properties, including significant antioxidant, antibacterial and cytocompatibility properties. In addition, experiments in a total skin defect model showed that this multifunctional gel film accelerates wound healing and promotes skin regeneration. These results suggest that the sprayable Ion2+-COS/SA multifunctional pro-healing gel film may be a promising candidate for the clinical treatment of allodermic wounds.


Assuntos
Alginatos , Cicatrização , Alginatos/química , Alginatos/farmacologia , Antibacterianos/química , Antibacterianos/farmacologia , Bandagens , Quitosana , Hidrogéis/química , Íons/farmacologia , Oligossacarídeos
17.
Int J Mol Sci ; 23(10)2022 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-35628537

RESUMO

In salt-sensitive plants, root hydraulic conductivity is severely inhibited by NaCl, rapidly leading to the loss of water balance. However, halophytic plants appear to effectively control plant water flow under salinity conditions. In this study, we tested the hypothesis that Na+ is the principal salt factor responsible for the enhancement of aquaporin-mediated water transport in the roots of halophytic grasses, and this enhancement plays a significant role in the maintenance of water balance, gas exchange, and the growth of halophytic plants exposed to salinity. We examined the effects of treatments with 150 mM of NaCl, KCl, and Na2SO4 to separate the factors that affect water relations and, consequently, physiological and growth responses in three related grass species varying in salt tolerance. The grasses included relatively salt-sensitive Poa pratensis, moderately salt-tolerant Poa juncifolia, and the salt-loving halophytic grass Puccinellia nuttalliana. Our study demonstrated that sustained growth, chlorophyll concentrations, gas exchange, and water transport in Puccinellia nuttalliana were associated with the presence of Na in the applied salt treatments. Contrary to the other examined grasses, the root cell hydraulic conductivity in Puccinellia nuttalliana was enhanced by the 150 mM NaCl and 150 mM Na2SO4 treatments. This enhancement was abolished by the 50 µM HgCl2 treatment, demonstrating that Na was the factor responsible for the increase in mercury-sensitive, aquaporin-mediated water transport. The observed increases in root Ca and K concentrations likely played a role in the transcriptional and (or) posttranslational regulation of aquaporins that enhanced root water transport capacity in Puccinellia nuttalliana. The study demonstrates that Na plays a key role in the aquaporin-mediated root water transport of the halophytic grass Puccinellia nuttalliana, contributing to its salinity tolerance.


Assuntos
Aquaporinas , Poa , Íons/farmacologia , Raízes de Plantas/metabolismo , Poa/metabolismo , Tolerância ao Sal , Plantas Tolerantes a Sal/metabolismo , Sódio/metabolismo , Cloreto de Sódio/farmacologia , Água/metabolismo
18.
Int J Mol Sci ; 23(9)2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35563256

RESUMO

Concurrent exposure to ionizing radiation (IR) and psychological stress (PS) may affect the development of adverse health consequences in scenarios such as space missions, radiotherapy and nuclear accidents. IR can induce DNA damage and cell apoptosis in the kidneys, thus potentially leading to renal fibrosis, which is the ultimate outcome of various chronic progressive nephropathies and the morphological manifestation of a continuous coordinated response after renal injury. However, little is known regarding the effects of concurrent IR exposure and PS on renal damage, particularly renal fibrosis. In this study, using a chronic restraint-induced PS (CRIPS) model, we exposed Trp53-heterozygous mice to total body irradiation with 0.1 or 2 Gy 56Fe ions on the eighth day of 28 consecutive days of a restraint regimen. At the end of the restraint period, the kidneys were collected. The histopathological changes and the degree of kidney fibrosis were assessed with H&E and Masson staining, respectively. Fibronectin (FN) and alpha smooth muscle actin (α-SMA), biomarkers of fibrosis, were detected by immunohistochemistry. Analysis of 8-hydroxy-2 deoxyguanosine (8-OHdG), a biomarker of oxidative DNA damage, was performed with immunofluorescence, and terminal deoxynucleotidyl transferase-mediated nick end labeling assays were used to detect apoptotic cells. Histopathological observations did not indicate significant structural damage induced by IR or CRIPS + IR. Western blotting revealed that the expression of α-SMA was much higher in the CRIPS + IR groups than the CRIPS groups. However, no differences in the average optical density per area were observed for FN, α-SMA and 8-OHdG between the IR and CRIPS + IR groups. No difference in the induction of apoptosis was observed between the IR and CRIPS + IR groups. These results suggested that exposure to IR (0.1 and 2 Gy 56Fe ions), 28 consecutive days of CRIPS or both did not cause renal fibrosis. Thus, CRIPS did not alter the IR-induced effects on renal damage in Trp53-heterozygous mice in our experimental setup.


Assuntos
Nefropatias , Irradiação Corporal Total , 8-Hidroxi-2'-Desoxiguanosina , Animais , Apoptose , Feminino , Fibrose , Humanos , Íons/farmacologia , Ferro/farmacologia , Rim/patologia , Nefropatias/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL
19.
Int J Mol Sci ; 23(14)2022 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-35887366

RESUMO

Coumarin is highly distributed in nature, notably in higher plants. The biological features of coumarin include antibacterial, anticancer and antioxidant effects. It is well known that metal ions present in complexes accelerate the drug action and the efficacy of organic therapeutic agents. The main aim of the current study is the synthesis of different complexes of the interaction between ciprofloxacin hydrochloride (CIP) and coumarin derivative 7-hydroxy-4-methylcoumarin (HMC) with Zr(IV). The chelates of CIP with Zr(IV) were prepared and characterized by elemental analysis, melting point, conductance measurements, spectroscopic techniques involving IR, UV-Vis, 1H NMR, and thermal behavior (TG-DTG) in the presence of HMC, dimethylformamide (DMF), pyridine (Py), and triethylamine (Et3N). Results of molar conductivity tests showed that the new synthesized complexes are electrolytes with a 1:1 or 1:2 electrolyte ratio, with the chloride ions functioning as counter ions. According to IR spectra, CIP acts as a neutral bidentate ligand with Zr(IV) through one carboxylato oxygen and the carbonyl group, HMC as a monodentate through the carbonyl group, and DMF through the oxygen atom of the carbonyl group and the N atom of Py and Et3N. The thermal behavior of the complexes was carefully investigated using TG and DTG techniques. TG findings signal that water molecules are found as hydrated and coordinated. The thermal decomposition mechanisms proposed for CIP, HMC, and Zr(IV) complexes are discussed and the activation energies (Ea), Gibbs free energies (∆G*), entropies (∆S*), and enthalpies (∆H*) of thermal decomposition reactions have been calculated using Coats-Redfern (CR) and Horowitz-Metzeger (HM) methods. The studied complexes were tested against some human pathogens and phytopathogens, including three Gram-positive bacteria (Bacillus subtilis, B. cereus, Brevibacterium otitidis) and three Gram-negative bacteria (Escherichiacoli, Pseudomonas aeruginosa and Klebsiella pneumoniae), and compared to the free CIP and HMC parent compounds.


Assuntos
Ciprofloxacina , Complexos de Coordenação , Antibacterianos/química , Antibacterianos/farmacologia , Bactérias , Ciprofloxacina/farmacologia , Complexos de Coordenação/química , Cumarínicos/farmacologia , Humanos , Íons/farmacologia , Ligantes , Testes de Sensibilidade Microbiana , Oxigênio/farmacologia , Espectrofotometria Infravermelho
20.
Prep Biochem Biotechnol ; 52(9): 1087-1095, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35112660

RESUMO

BACKGROUND: In the past few years, the production of shrimp shell waste from the seafood processing industries has confronted a significant surge. Furthermore, insignificant dumping of waste has dangerous effects on both nature and human well-being. This marine waste contains a huge quantity of chitin which has several applications in different fields. The chitinase enzyme can achieve degradation of chitin, and the chitin itself can be used as the substrate as well for production of chitinase. In the current study, the chitinase enzyme was produced by Thermomyces lanuginosus. The extracellular chitinase was purified from crude extract using ammonium sulfate precipitation followed by DEAE-cellulose ion-exchange chromatography and Sephadex G-100 gel filtration chromatography. The stability and activity of chitinase with different pH, temperature, different times for a reaction, in the presence of different metal ions, and different concentration of enzyme and substrate were analyzed. RESULT: The chitinase activity was found to be highest at pH 6.5, 50 °C, and 60 min after the reaction began. and the chitinase showed the highest activity and stability in the presence of ß-mercaptoethanol (ME). The SDS-PAGE of denatured purified chitinase showed a protein band of 18 kDa. CONCLUSION: The characterization study concludes that Cu2+, Hg2+, and EDTA have an inhibitory effect on chitinase activity, whereas ß-ME acts as an activator for chitinase activity. The utilization of chitin to produce chitinase and the degradation of chitin using that chitinase enzyme would be an opportunity for bioremediation of shrimp shell waste.


Assuntos
Quitinases , Mercúrio , Sulfato de Amônio , Quitina/metabolismo , Quitinases/metabolismo , Misturas Complexas/farmacologia , DEAE-Celulose/farmacologia , Ácido Edético , Estabilidade Enzimática , Eurotiales , Fungos/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Íons/farmacologia , Mercaptoetanol/farmacologia , Temperatura
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