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1.
Environ Sci Pollut Res Int ; 31(11): 16375-16387, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38315336

ABSTRACT

Intensive sulphur fertilisation has been reported to improve the nutrient balance and growth of Cd-exposed plants, but the reasons of this phenomenon and the role of sulphur compounds in the resistance to cadmium are unclear. We investigated sulphur supplementation-induced changes in the surface properties of roots and the level of thiol peptides (PCs) in Cd-stressed Triticum aestivum L. (monocots clade) and Lactuca sativa L. (dicots clade) grown in nutrient solution. The combination of three sulphur (2 mM S-basic level, 6 or 9 mM S-elevated levels) and four cadmium (0, 0.0002, 0.02 or 0.04 mM Cd) concentrations was used. The physicochemical parameters of the roots were determined based on the apparent surface area (Sr), total variable surface charge (Q), cation exchange capacity (CEC) and surface charge density (SCD). In Cd-exposed plants supplied with sulphur, a different character and trend in the physicochemical changes (adsorption and ion exchange) of roots were noted. At the increased sulphur levels, as a rule, the Sr, CEC, Q and SCD values clearly increased in the lettuce but decreased in the wheat in the entire range of the Cd concentrations, except the enhanced Sr of wheat supplied with 6 mM S together with elevated (0.0002 mM) and unchanged (0.02, 0.04 mM Cd) value of this parameter at 9 mM S. This indicates a clade-specific and/or species-specific plant reaction. The 6 mM S appears to be more effective than 9 mM S in alleviation of the cadmium's toxic effects on roots. It was found that at 0.02 and 0.04 mM Cd, the use of 6 mM S limits the Cd accumulation in the roots of both species in comparison with the basic S fertilisation. Moreover, PC accumulation was much more efficient in wheat than in lettuce, and intensive sulphur nutrition generally induced biosynthesis of these chelating compounds. Physicochemical parameters together with quantitative and qualitative assessment of thiol peptides can be important indicators of the efficiency of root system functioning under cadmium stress. The differences between the species and the multidirectional character of the changes are a result of the involvement of a number of multi-level mechanisms engaged in the defence against metal toxicity.


Subject(s)
Phytochelatins , Soil Pollutants , Cadmium/toxicity , Lactuca , Triticum , Sulfur/pharmacology , Sulfhydryl Compounds , Dietary Supplements , Plant Roots , Soil Pollutants/pharmacology
2.
Chemosphere ; 351: 141265, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38246497

ABSTRACT

Plant enrichment and tolerance to heavy metals are crucial for the phytoremediation of coal gangue mountain. However, understanding of how plants mobilize and tolerate heavy metals in coal gangue is limited. This study conducted potted experiments using Setaria viridis as a pioneer remediation plant to evaluate its tolerance to coal gangue, its mobilization and enrichment of metals, and its impact on the soil environment. Results showed that the addition of 40% gangue enhanced plant metal and oxidative stress resistance, thereby promoting plant growth. However, over 80% of the gangue inhibited the chlorophyll content, photoelectron conduction rate, and biomass of S. viridis, leading to cellular peroxidative stress. An analysis of metal resistance showed that endogenous S in coal gangue promoted the accumulation of glutathione, plant metal chelators, and non-protein thiols, thereby enhancing its resistance to metal stress. Setaria viridis cultivation affected soil properties by decreasing nitrogen, phosphorus, conductivity, and urease and increasing sucrase and acid phosphatase in the rhizosphere soil. In addition, S. viridis planting increased V, Cr, Ni, As, and Zn in the exchangeable and carbonate-bound states within the gangue, effectively enriching Cd, Cr, Fe, S, U, Cu, and V. The increased mobility of Cd and Pb was correlated with a higher abundance of Proteobacteria and Acidobacteria. Heavy metals, such as As, Fe, V, Mn, Ni, and Cu, along with environmental factors, including total nitrogen, total phosphorus, urease, and acid phosphatase, were the primary regulatory factors for Sphingomonas, Gemmatimonas, and Bryobacter. In summary, S. viridis adapted to gangue stress by modulating antioxidant and elemental enrichment systems and regulating the release and uptake of heavy metals through enhanced bacterial abundance and the recruitment of gangue-tolerant bacteria. These findings highlight the potential of S. viridis for plant enrichment in coal gangue areas and will aid the restoration and remediation of these environments.


Subject(s)
Metals, Heavy , Setaria Plant , Soil Pollutants , Cadmium/pharmacology , Setaria Plant/metabolism , Coal , Urease , Metals, Heavy/analysis , Plants/metabolism , Phosphorus/pharmacology , Bacteria/metabolism , Sulfur/pharmacology , Soil , Acid Phosphatase , Nitrogen/pharmacology , Soil Pollutants/analysis
3.
Sci Rep ; 13(1): 6858, 2023 04 26.
Article in English | MEDLINE | ID: mdl-37100855

ABSTRACT

The present study demonstrated that exogenously-sourced nitric oxide (as SNP, sodium nitroprusside; NO donor) and sulfur (S) protected photosynthesis against chromium (Cr) stress in wheat (Triticum aestivum L. cv. HD 2851). Plants grown with 100 µM Cr exhibited higher reactive oxygen species (ROS) production, resulting in photosynthetic damage. The individual application of 50 µM NO increased carbohydrate metabolism as well as photosynthetic parameters, antioxidant system with higher transcriptional gene levels that encode the key enzymes for the Calvin cycle under Cr stress. These effects were more prominent when NO was applied with 1.0 mM SO42-. An increase in the reduced glutathione (GSH) content obtained with NO was further enhanced by S and resulted in higher protection against Cr stress. The protective effect of NO with S against Cr toxicity on photosynthesis was reversed when buthionine sulfoximine (BSO; GSH biosynthetic inhibitor) was used. Application of BSO reversed the impact of NO plus S on photosynthesis under Cr stress, verifying that the ameliorating effect of NO was through S-assimilation and via GSH production. Thus, the availability of S to NO application can help reduce Cr toxicity and protect photosynthetic activity and expression of the Calvin cycle enzymes in leaves through the GSH involvement.


Subject(s)
Chromium , Nitric Oxide , Chromium/toxicity , Chromium/metabolism , Nitric Oxide/metabolism , Triticum/metabolism , Photosynthesis , Carbohydrate Metabolism , Antioxidants/metabolism , Glutathione/metabolism , Sulfur/pharmacology , Sulfur/metabolism , Dietary Supplements , Oxidative Stress
4.
J Anim Physiol Anim Nutr (Berl) ; 107(2): 435-443, 2023 Mar.
Article in English | MEDLINE | ID: mdl-35686542

ABSTRACT

This study aimed to study the effect of excessive elemental sulfur addition on intake, digestibility, rumen characteristics, blood metabolites and nitrogen balance in Thai native beef cattle fed diets containing high fresh cassava root (FCR) supplementation. Four Thai native beef cattle with an initial body weight (BW) of 100 ± 10.0 kg were used and randomly assigned to a 2 × 2 factorial in a 4 × 4 Latin square design. Two levels of FCR supplementation at 15 (FCR-1.5) and 20 g/kg of BW (FCR-2) and two levels of sulfur supplementation in concentrate at 10 (Sulfur-1) and 20 g/kg dry matter concentrate (Sulfur-2) were evaluated. This study showed that sulfur and FCR in combination (p < 0.05) increased dry matter and organic matter digestibility and bacterial population. Sulfur-2 resulted in higher (p < 0.05) sulfur intake and serum thiocyanate concentration than Sulfur-1. FCR-2 had a greater (p < 0.05) FCR intake, total volatile fatty acids and propionate concentration than FCR-1.5. In conclusion, excessive elemental sulfur addition with high FCR supplementation showed no negative effect in Thai native beef cattle.


Subject(s)
Dietary Supplements , Manihot , Animals , Cattle , Animal Feed/analysis , Diet/veterinary , Digestion , Eating , Fermentation , Nitrogen/metabolism , Rumen/metabolism , Sulfur/metabolism , Sulfur/pharmacology
5.
Molecules ; 27(19)2022 Sep 27.
Article in English | MEDLINE | ID: mdl-36234903

ABSTRACT

Red onion, a species of great economic importance rich in phytochemicals (bioactive compounds) known for its medicinal properties, was fertilized with sulphur-bentonite enriched with orange residue or olive pomace, with the aim of producing onion enriched in health beneficial compounds. There is a worldwide great demand of minimally processed food or food ingredients with functional properties because of a new awareness of how important healthy functional nutrition is in life. Phytochemicals have the capacity to regulate most of the metabolic processes resulting in health benefits. Red onion bioactive compound quantity and quality can vary according to cultivation practices. The main aims of the current research were to determine the chemical characteristics of the crude extracts from red onion bulbs differently fertilized and to evaluate their biological activity in normal and oxidative stress conditions. The lyophilized onion bulbs have been tested in vitro on two cellular models, i.e., the H9c2 rat cardiomyoblast cell line and primary human dermal fibroblasts, in terms of viability and oxygen radical homeostasis. The results evidenced different phytochemical compositions and antioxidant activities of the extracts obtained from red onions differently fertilized. Sulphur-bentonite fertilizers containing orange waste and olive pomace positively affected the red onion quality with respect to the red onion control, evidencing that sulphur-bentonite-organic fertilization was able to stimulate plant a secondary metabolism inducing the production of phytochemicals with healthy functions. A positive effect of the extracts from red onions treated with fertilizers-in particular, with those containing orange waste, such as the reduction of oxidative stress and induction of cell viability of H9c2 and human fibroblasts-was observed, showing a concentration- and time-dependent profile. The results evidenced that the positive effects were related to the phenols and, in particular, to chlorogenic and p-coumaric acids and to the flavonol kaempferol, which were more present in red onion treated with low orange residue than in the other treated ones.


Subject(s)
Food Ingredients , Olea , Animals , Antioxidants/metabolism , Antioxidants/pharmacology , Bentonite , Coumaric Acids/pharmacology , Fertilizers , Humans , Kaempferols/pharmacology , Mammals/metabolism , Olea/metabolism , Onions/chemistry , Oxidative Stress , Phenols/pharmacology , Phytochemicals/metabolism , Phytochemicals/pharmacology , Plant Extracts/chemistry , Plant Extracts/pharmacology , Rats , Reactive Oxygen Species/metabolism , Sulfur/pharmacology
6.
Antimicrob Agents Chemother ; 66(9): e0059222, 2022 09 20.
Article in English | MEDLINE | ID: mdl-35975988

ABSTRACT

Moxifloxacin is central to treatment of multidrug-resistant tuberculosis. Effects of moxifloxacin on the Mycobacterium tuberculosis redox state were explored to identify strategies for increasing lethality and reducing the prevalence of extensively resistant tuberculosis. A noninvasive redox biosensor and a reactive oxygen species (ROS)-sensitive dye revealed that moxifloxacin induces oxidative stress correlated with M. tuberculosis death. Moxifloxacin lethality was mitigated by supplementing bacterial cultures with an ROS scavenger (thiourea), an iron chelator (bipyridyl), and, after drug removal, an antioxidant enzyme (catalase). Lethality was also reduced by hypoxia and nutrient starvation. Moxifloxacin increased the expression of genes involved in the oxidative stress response, iron-sulfur cluster biogenesis, and DNA repair. Surprisingly, and in contrast with Escherichia coli studies, moxifloxacin decreased expression of genes involved in respiration, suppressed oxygen consumption, increased the NADH/NAD+ ratio, and increased the labile iron pool in M. tuberculosis. Lowering the NADH/NAD+ ratio in M. tuberculosis revealed that NADH-reductive stress facilitates an iron-mediated ROS surge and moxifloxacin lethality. Treatment with N-acetyl cysteine (NAC) accelerated respiration and ROS production, increased moxifloxacin lethality, and lowered the mutant prevention concentration. Moxifloxacin induced redox stress in M. tuberculosis inside macrophages, and cotreatment with NAC potentiated the antimycobacterial efficacy of moxifloxacin during nutrient starvation, inside macrophages, and in mice, where NAC restricted the emergence of resistance. Thus, NADH-reductive stress contributes to moxifloxacin-mediated killing of M. tuberculosis, and the respiration stimulator (NAC) enhances lethality and suppresses the emergence of drug resistance.


Subject(s)
Mycobacterium tuberculosis , Tuberculosis , 2,2'-Dipyridyl/pharmacology , Animals , Antioxidants/pharmacology , Catalase , Cysteine , Iron , Iron Chelating Agents/pharmacology , Mice , Moxifloxacin/pharmacology , NAD , Reactive Oxygen Species/metabolism , Sulfur/pharmacology , Thiourea , Tuberculosis/microbiology
7.
ACS Nano ; 16(7): 11204-11217, 2022 07 26.
Article in English | MEDLINE | ID: mdl-35792576

ABSTRACT

Nanoscale sulfur can be a multifunctional agricultural amendment to enhance crop nutrition and suppress disease. Pristine (nS) and stearic acid coated (cS) sulfur nanoparticles were added to soil planted with tomatoes (Solanum lycopersicum) at 200 mg/L soil and infested with Fusarium oxysporum. Bulk sulfur, ionic sulfate, and healthy controls were included. Orthogonal end points were measured in two greenhouse experiments, including agronomic and photosynthetic parameters, disease severity/suppression, mechanistic biochemical and molecular end points including the time-dependent expression of 13 genes related to two S bioassimilation and pathogenesis-response, and metabolomic profiles. Disease reduced the plant biomass by up to 87%, but nS and cS amendment significantly reduced disease as determined by area-under-the-disease-progress curve by 54 and 56%, respectively. An increase in planta S accumulation was evident, with size-specific translocation ratios suggesting different uptake mechanisms. In vivo two-photon microscopy and time-dependent gene expression revealed a nanoscale-specific elemental S bioassimilation pathway within the plant that is separate from traditional sulfate accumulation. These findings correlate well with time-dependent metabolomic profiling, which exhibited increased disease resistance and plant immunity related metabolites only with nanoscale treatment. The linked gene expression and metabolomics data demonstrate a time-sensitive physiological window where nanoscale stimulation of plant immunity will be effective. These findings provide mechanistic understandings of nonmetal nanomaterial-based suppression of plant disease and significantly advance sustainable nanoenabled agricultural strategies to increase food production.


Subject(s)
Solanum lycopersicum , Sulfur/pharmacology , Plant Diseases/prevention & control , Soil/chemistry , Plants/metabolism , Sulfates/metabolism
8.
ACS Appl Bio Mater ; 5(5): 2316-2323, 2022 05 16.
Article in English | MEDLINE | ID: mdl-35468281

ABSTRACT

Biopolymer-based functional blend films were prepared using pullulan and gelatin with functional fillers of sulfur nanoparticles (SNPs) and grape seed extract (GSE). A mixture of pullulan/gelatin (1:1) produced a compatible but slightly translucent free-standing film. SNPs capped with enoki mushroom extract and GSE were added as functional fillers to improve the properties (physical and functional) of the pullulan/gelatin-based film. The addition of SNP and GSE significantly (p < 0.05) boosted the UV-light barrier, water vapor barrier, and oxygen barrier properties of the pullulan/gelatin films. The mechanical performance of the pullulan/gelatin-based films was slightly decreased (∼10%), whereas the addition of fillers did not significantly affect the hydrophobicity and thermal stability. The addition of SNP provided the antimicrobial function against foodborne pathogenic bacteria, L. monocytogenes and E. coli, while GSE provided a powerful antioxidant activity to the pullulan/gelatin-based film. Therefore, pullulan/gelatin-based composite films with better UV, water vapor, and oxygen barrier properties and enhanced antioxidant and antibacterial properties are expected to have high utility in active food packaging applications.


Subject(s)
Anti-Infective Agents , Grape Seed Extract , Nanoparticles , Anti-Bacterial Agents/pharmacology , Anti-Infective Agents/pharmacology , Antioxidants/pharmacology , Escherichia coli , Gelatin/pharmacology , Glucans , Grape Seed Extract/pharmacology , Oxygen , Steam , Sulfur/pharmacology
9.
Environ Sci Pollut Res Int ; 29(42): 64205-64214, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35469387

ABSTRACT

The current study was conducted to investigate the role of sulfur (S) and reduced glutathione (GSH) in mitigating arsenic (As) toxicity in Isatis cappadocica and Erysimum allionii. These plants were exposed for 3 weeks to different concentrations (0, 400 and 800 µM) of As to measure fresh weight, total chlorophyll, proline and hydrogen peroxide (H2O2) content, As and S accumulation, and guaiacol peroxidase (POD) and glutathione S-transferase (GST) along with the supplementation of 20 mg L-1 of S and 500 µM of GSH. Results revealed the significant reduction of fresh weight (especially in E. allionii), activities of POD and GST enzymes and proline content as compare to control. However, the application of S and GSH enhanced the fresh weight. Inhibition in H2O2 accumulation and improvement in antioxidant responses were measured with the application of S and GSH. Hence, the supplementation of S and GSH enhanced fresh weight and total chlorophyll in both I. cappadocica and E. allionii by alleviating the adverse effects of As stress via decreased H2O2 content and restricted As uptake.


Subject(s)
Arsenic , Erysimum , Isatis , Antioxidants/metabolism , Arsenic/toxicity , Chlorophyll/pharmacology , Dietary Supplements , Erysimum/metabolism , Glutathione/metabolism , Glutathione Transferase , Hydrogen Peroxide/pharmacology , Isatis/physiology , Oxidative Stress , Proline/metabolism , Seedlings , Sulfur/pharmacology
10.
Homeopathy ; 111(4): 271-277, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35259770

ABSTRACT

BACKGROUND: Myiasis by Cochliomyia hominivorax (Diptera: Calliphoridae) is a serious problem in animal health in tropical and sub-tropical regions. Ointment-type preparations are a good option of formulation in cases of myiasis in farm and pet animals. Sulphur and Pyrogenium have already shown in-vitro efficacy on C. hominivorax. This article describes an in-vitro experiment to test the inhibition of development from exposing larvae of C. hominivorax to two homeopathic ointments (prepared individually with Sulphur or Pyrogenium). METHODS: The homeopathic ointments were produced by mixing sterile lanolin, tocopherol and homeopathic medicine on a hydroalcoholic basis according to the Brazilian Homeopathic Pharmacopoeia. Larvae were obtained from naturally occurring myiases in sheep (wild larvae) or from a laboratory colony. The test consisted of exposing a group of 10 third-stage C. hominivorax wild larvae in contact with Sulphur or Pyrogenium ointment, or a group of 15 laboratory-propagated larvae in contact with the alcoholic vehicle of the ointment or homeopathic medicines prepared in sterile water (Sulphur or Pyrogenium), and observing the effect on the development, longevity and fertility of the blow-fly specimens. RESULTS: The C. hominivorax larval inhibition rate was 90.0% for the Sulphur ointment group and was 86.0% for the Pyrogenium ointment group. The non-alcoholic vehicle and the alcoholic vehicle inhibited the development of 24.0% and 22.08% of the larvae respectively. Sulphur prepared in sterile water inhibited the development of 74.67% and Pyrogenium in sterile water inhibited 73.33% of larvae. Specimens that survived contact with homeopathic ointments had their longevity decreased and did not reproduce. CONCLUSION: Ointments of Sulphur or Pyrogenium were able to inhibit the development of C. hominivorax larvae. The ointment vehicle was harmless.


Subject(s)
Diptera , Homeopathy , Materia Medica , Myiasis , Animals , Sheep , Calliphoridae , Larva , Ointments/pharmacology , Myiasis/veterinary , Sulfur/pharmacology , Materia Medica/pharmacology , Water
11.
ACS Appl Mater Interfaces ; 14(4): 4980-4994, 2022 Feb 02.
Article in English | MEDLINE | ID: mdl-35050589

ABSTRACT

Regulating the level of reactive oxygen species (ROS) in a tumor is an efficient and innovative anticancer strategy. However, the therapeutic efficacy of ROS-based therapies, such as chemodynamic therapy (CDT) and photodynamic therapy (PDT), offers finite outcomes due to the oxygen dependence and limited concentration of hydrogen peroxide (H2O2) and overexpression of glutathione (GSH) within the tumor microenvironment (TME), so a single therapeutic strategy is insufficient to completely eliminate tumors. Therefore, we demonstrated an omnipotent nanoplatform MnO2/Ag3SbS3 (abbreviated as MA) with strong optical absorbance in the NIR-II biowindow and oxygen self-sufficient ROS-mediated ability, which not only relieves tumor hypoxia significantly but also enhances the photothermal therapy (PTT)/PDT/CDT efficacy. By 1064 nm laser irradiation, MnO2/Ag3SbS3 nanoparticles (NPs) reveal a favorable photothermal conversion efficiency of 23.15% and achieve a single-laser-triggered NIR-II PTT/PDT effect, resulting in effective tumor elimination. Once internalized into the tumor, MnO2/Ag3SbS3 NPs will be degraded to Mn2+ and Ag3SbS3. The released Ag3SbS3 NPs as a NIR-II phototherapy agent could be utilized for photoacoustic imaging-guided NIR-II PDT/PTT. Mn2+ could be used as a Fenton-like catalyst to continuously catalyze endogenous H2O2 for generating highly virulent hydroxyl radicals (•OH) for CDT and O2 for PDT, enhancing the efficiency of PDT and CDT, respectively. Meanwhile, Mn2+ realizes magnetic resonance imaging-guided accurate tumor therapy. Moreover, the MnO2/Ag3SbS3 NPs could deplete intracellular GSH in TME to promote oxidative stress of the tumor, further strengthening ROS-mediated antitumor treatment efficacy. Overall, this work presents a distinctive paradigm of TME-responsive PDT/CDT/PTT in the second near-infrared biowindow by depleting GSH and decomposing H2O2 for efficient and precise cancer treatment.


Subject(s)
Antineoplastic Agents/pharmacology , Biocompatible Materials/pharmacology , Lasers , Photosensitizing Agents/pharmacology , Theranostic Nanomedicine , Animals , Antimony/chemistry , Antimony/pharmacology , Antineoplastic Agents/chemistry , Biocompatible Materials/chemistry , Cell Proliferation/drug effects , Cell Survival/drug effects , Drug Screening Assays, Antitumor , Infrared Rays , Manganese Compounds/chemistry , Manganese Compounds/pharmacology , Materials Testing , Mice , Oxides/chemistry , Oxides/pharmacology , Particle Size , Photochemotherapy , Photosensitizing Agents/chemistry , Silver/chemistry , Silver/pharmacology , Sulfur/chemistry , Sulfur/pharmacology , Surface Properties , Tumor Cells, Cultured
12.
Eur J Med Chem ; 227: 113892, 2022 Jan 05.
Article in English | MEDLINE | ID: mdl-34678572

ABSTRACT

Selenium is an underexplored element that can be used for bioisosteric replacement of lower molecular weight chalcogens such as oxygen and sulfur. More studies regarding the impact of selenium substitution in different chemical scaffolds are needed to fully grasp this element's potential. Herein, we decided to evaluate the impact of selenium incorporation in a series of tryptophan 2,3-dioxygenase (TDO2) inhibitors, a target of interest in cancer immunotherapy. First, we synthesized the different chalcogen isosteres through Suzuki-Miyaura type coupling. Next, we evaluated the isosteres' affinity and selectivity for TDO2, as well as their lipophilicity, microsomal stability and cellular toxicity on TDO2-expressing cell lines. Overall, chalcogen isosteric replacements did not disturb the on-target activity but allowed for a modulation of the compounds' lipophilicity, toxicity and stability profiles. The present work contributes to our understanding of oxygen/sulfur/selenium isostery towards increasing structural options in medicinal chemistry for the development of novel and distinctive drug candidates.


Subject(s)
Chalcogens/pharmacology , Enzyme Inhibitors/pharmacology , Heterocyclic Compounds/pharmacology , Selenium/pharmacology , Tryptophan Oxygenase/antagonists & inhibitors , Chalcogens/chemistry , Dose-Response Relationship, Drug , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Heterocyclic Compounds/chemical synthesis , Heterocyclic Compounds/chemistry , Humans , Molecular Structure , Oxygen/chemistry , Oxygen/pharmacology , Selenium/chemistry , Stereoisomerism , Structure-Activity Relationship , Sulfur/chemistry , Sulfur/pharmacology , Tryptophan Oxygenase/metabolism
13.
Molecules ; 26(23)2021 Dec 04.
Article in English | MEDLINE | ID: mdl-34885946

ABSTRACT

In this work, we evaluated the conformational effect promoted by the isosteric exchange of sulfur by selenium in the heteroaromatic ring of new N-acylhydrazone (NAH) derivatives (3-8, 13, 14), analogues of the cardioactive compounds LASSBio-294 (1) and LASSBio-785 (2). NMR spectra analysis demonstrated a chemical shift variation of the iminic Csp2 of NAH S/Se-isosters, suggesting a stronger intramolecular chalcogen interaction for Se-derivatives. To investigate the pharmacological profile of these compounds at the adenosine A2A receptor (A2AR), we performed a previously validated functional binding assay. As expected for bioisosteres, the isosteric-S/Se replacement affected neither the affinity nor the intrinsic efficacy of our NAH derivatives (1-8). However, the N-methylated compounds (2, 6-8) presented a weak partial agonist profile at A2AR, contrary to the non-methylated counterparts (1, 3-5), which appeared as weak inverse agonists. Additionally, retroisosterism between aromatic rings of NAH on S/Se-isosters mimicked the effect of the N-methylation on intrinsic efficacy at A2AR, while meta-substitution in the phenyl ring of the acyl moiety did not. This study showed that the conformational effect of NAH-N-methylation and aromatic rings retroisosterism changed the intrinsic efficacy on A2AR, indicating the S/Se-chalcogen effect to drive the conformational behavior of this series of NAH.


Subject(s)
Hydrazones/chemistry , Receptor, Adenosine A2A/metabolism , Selenium/chemistry , Sulfur/chemistry , Thiophenes/chemistry , Adenosine A2 Receptor Agonists/chemistry , Adenosine A2 Receptor Agonists/pharmacology , Animals , Humans , Hydrazones/pharmacology , Male , Models, Molecular , Rats, Wistar , Selenium/pharmacology , Sulfur/pharmacology , Thiophenes/pharmacology
14.
BMC Vet Res ; 17(1): 304, 2021 Sep 09.
Article in English | MEDLINE | ID: mdl-34503491

ABSTRACT

BACKGROUND: Total fresh cassava root (FCR) production was 275 million tonnes in 2018 which equals 61.1 % of the total production, and Thailand produced 10.7 % FCR of the total production. FCR is one of the main energy source for ruminant. The limitation of FCR utilization is due to the presence of hydrogen cyanide (HCN). The study aimed to evaluate the effect of sulfur, urea and FCR at various levels on in vitro gas production, ruminal fermentation and in vitro degradability. The study hypothesized that: (1) sulfur, urea and FCR have no interaction effect and (2) effect of FCR and urea is related to sulfur addition. RESULTS: The study aimed to elucidate the optimum level of elemental sulfur, fresh cassava root (FCR) and urea and their effect on in vitro gas production, ruminal fermentation, thiocyanate concentration, and in vitro degradability. A 3 × 2 × 4 in a completely randomized design were conducted. Factor A was level of sulfur at 0 %, 1 and 2 % of concentrate dry matter (DM), factor B was level of urea at 2 and 4 % of concentrate DM, and factor C was level of the FCR at 0, 200, 300 and 400 mg DM of the total substrate. The study found that elemental sulfur, urea and FCR had no interaction effect on the kinetics of in vitro gas, ruminal fermentation, HCN and in vitro degradability. Elemental sulfur supplementation (P < 0.05) significantly increased the in vitro gas produced from an insoluble fraction (b), in vitro DM degradability and either neutral detergent fiber (NDF) or acid detergent fiber (ADF) degradability and propionate (C3) concentration while decreased the ruminal HCN concentration. Urea levels showed a (P < 0.05) significant increase of the potential extent of in vitro gas production, ruminal ammonia nitrogen (NH3-N) and total volatile fatty acid (TVFA). Fresh cassava root supplementation (P < 0.05) significantly increased the in vitro gas produced from an immediate soluble fraction (a), in vitro gas produced from insoluble fraction, in vitro gas production rate constant, total VFA, C3 concentration and HCN while decreased ruminal pH, acetate and butyrate concentration. It could be concluded that 2 % elemental sulfur, 4 % urea and 300 mg FCR showed a greater effect on in vitro gas production, ruminal fermentation and HCN reduction. CONCLUSIONS: The study found that elemental sulfur, urea, and FCR had no interaction effect on the kinetics of in vitro gas, total in vitro gas, ruminal fermentation, and HCN concentration. It could be concluded that 2 % elemental sulfur, 4 % urea, and 300 mg FCR showed a greater effect on in vitro gas production, ruminal fermentation, and HCN reduction.


Subject(s)
Animal Feed/analysis , Methane/metabolism , Plant Roots/metabolism , Rumen/drug effects , Sulfur/pharmacology , Urea/pharmacology , Animals , Dietary Supplements/analysis , Digestion/drug effects , Digestion/physiology , Fermentation/drug effects , Fermentation/physiology , Manihot/metabolism , Methane/analysis
15.
Gene ; 792: 145742, 2021 Aug 05.
Article in English | MEDLINE | ID: mdl-34051336

ABSTRACT

Given the complexity of nutrient stress responses and the availability of a few validated reference genes, we aimed to identify robust and stable reference genes for macronutrient stress in rice and soybean. Ten potential reference genes were evaluated using geNorm, NormFinder, BestKeeper, Comparative ΔCt method, and RefFinder algorithms under low and completely starved conditions of nitrogen (N), phosphorus (P), potassium (K), and sulphur (S). Results revealed distinct sets of reference gene pairs, showing stable expression under different experimental conditions. The gene pairs TIP41/UBC(9/10/18) and F-box/UBC10 were most stable in rice and soybean, respectively under N stress. Under P stress, UBC9/UBC10 in rice and F-Box/UBC10 in soybean were most stable. Similarly, TIP41/UBC10 in rice and RING FINGER/UBC9 in soybean were the best gene pairs under K stress while F-Box/TIP41 in rice and UBC9/UBC10 in soybean were the most stable gene pairs under S stress. These reference gene pairs were validated by quantifying the expression levels of high-affinity transporters like NRT2.1/NRT2.5, PT1, AKT1, and SULTR1 for N, P, K, and S stress, respectively. This study reiterates the importance of choosing reference genes based on crop species and the experimental conditions, in order to obtain concrete answers to missing links of gene regulation in response to macronutrient deficiencies.


Subject(s)
Gene Expression Regulation, Plant , Genes, Essential , Glycine max/genetics , Oryza/genetics , Plant Proteins/genetics , Stress, Physiological/genetics , Gene Expression Profiling , Hydroponics/methods , Nitrogen/deficiency , Nitrogen/pharmacology , Oryza/drug effects , Oryza/growth & development , Oryza/metabolism , Phosphorus/deficiency , Phosphorus/pharmacology , Plant Proteins/classification , Plant Proteins/metabolism , Potassium/pharmacology , Potassium Deficiency/metabolism , Reference Standards , Seedlings/drug effects , Seedlings/genetics , Seedlings/growth & development , Seedlings/metabolism , Glycine max/drug effects , Glycine max/growth & development , Glycine max/metabolism , Sulfur/deficiency , Sulfur/pharmacology
16.
Pharm Biol ; 59(1): 40-46, 2021 Dec.
Article in English | MEDLINE | ID: mdl-33399496

ABSTRACT

CONTEXT: The traditional drying method, sun drying, for Chrysanthemum morifolium Ramat. cv. Hang-ju (Compositae) (HJ) is widely replaced by sulphur fumigation (SF), which has an unknown effect on its efficacy. OBJECTIVE: To investigate protective effects of nonfumigated HJ (NHJ) and sulphur-fumigated HJ (SHJ) water extracts against oxidative stress and lipid peroxidation. MATERIALS AND METHODS: Sprague-Dawley rats were administered high-fat diet to induce hyperlipidaemia and randomly divided into eight groups (n = 6): control, fenofibrate, NHJ and SHJ extracts (1, 2 or 4 g crude drugs/kg/d; intragastric administration for 8 weeks). Serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), superoxide dismutase (SOD) and malondialdehyde (MDA) levels were detected. Human umbilical vein endothelial cells (HUVECs) were treated with NHJ and SHJ extracts (50, 100 or 200 µg/mL) for 24 h, followed by oxidized low-density lipoprotein (ox-LDL, 20 µg/mL) for 2 h in vitro. Cellular reactive oxygen species (ROS), SOD and MDA levels and apoptosis were evaluated. RESULTS: NHJ was more effective than SHJ in decreasing serum TG, TC, LDL-C, LDL/HDL and MDA while increasing serum HDL-C and SOD levels at high doses. SHJ (IC50=19.9 mg/mL) suppressed HUVEC growth stronger than NHJ (IC50=186.7 mg/mL). At 200 µg/mL, NHJ was more effective than SHJ in downregulating ROS and MDA levels, reducing HUVECs apoptosis rate and elevating SOD activity in ox-LDL-treated HUVECs. CONCLUSIONS: SF causes oxidative damage and attenuates antioxidative activity in ox-LDL-treated HUVECs, which promotes lipid peroxidation. SF is not recommended for processing HJ.


Subject(s)
Antioxidants/pharmacology , Chrysanthemum , Fumigation/methods , Oxidative Stress/drug effects , Plant Extracts/pharmacology , Sulfur/pharmacology , Animals , Antioxidants/isolation & purification , Dose-Response Relationship, Drug , Human Umbilical Vein Endothelial Cells/drug effects , Human Umbilical Vein Endothelial Cells/metabolism , Humans , Male , Oxidative Stress/physiology , Plant Extracts/isolation & purification , Rats , Rats, Sprague-Dawley
17.
Ecotoxicol Environ Saf ; 208: 111643, 2021 Jan 15.
Article in English | MEDLINE | ID: mdl-33396163

ABSTRACT

Sulfur (S) can play essential roles in protecting plants against abiotic stress, including heavy metal toxicity. However, the effect of this nutrient on plants exposed to barium (Ba) is still unknown. This study was designed to evaluate the S supply on oxidative stress and the antioxidant system of Tanzania guinea grass under exposure to Ba, grown in a nutrient solution under greenhouse conditions. It was studied the influence of S/Ba combinations in nutrient solution on oxidative stress indicators (hydrogen peroxide, malondialdehyde, and proline) and antioxidant enzyme activities (superoxide dismutase, catalase, ascorbate peroxidase, guaiacol peroxidase, and glutathione reductase). The treatments consisted in thirteen S/Ba combinations in the nutrient solution (0.1/0.0; 0.1/5.0; 0.1/20.0; 1.0/2.5; 1.0/10.0; 1.9/0.0 - control; 1.9/5.0; 1.9/20.0; 2.8/2.5; 2.8/10.0; 3.7/0.0; 3.7/5.0 and 3.7/20.0 mM of S and Ba, respectively). The plants were grown for two growth periods, which consisted of fourteen days of S supply and the eight days of Ba exposure each one. The severe S deficiency decreased the superoxide dismutase activity, regardless of Ba exposure in recently expanded leaves and culms plus sheaths. However, supplemental S supply (above 1.9 mM S, which corresponds to S supply adequate to plant growth) it improved the superoxide dismutase activity in these tissues under high Ba concentrations. Conversely, the severe S deficiency increased the activities of catalase, ascorbate peroxidase, and glutathione reductase in grass leaves slightly, without Ba exposure influence. It was observed that the supplemental S supply also induced the guaiacol peroxidase activity and proline production in culms plus sheaths under high Ba rates, showing values until 2.5 and 3.1 folds higher than the control treatment, respectively. In plants under exposure to 20.0 mM Ba, the supplemental S supply decreased the malondialdehyde content in culms plus sheaths in 17% compared to 1.9 mM S. These results indicate that supplemental S supply can mitigate Ba toxicity in Tanzania guinea grass, mainly by improving superoxide dismutase and guaiacol peroxidase activities, and proline metabolism.


Subject(s)
Antioxidants/metabolism , Barium/toxicity , Panicum/drug effects , Proline/metabolism , Sulfur/pharmacology , Fertilizers , Oxidative Stress/drug effects , Panicum/growth & development , Panicum/metabolism , Peroxidase/metabolism , Plant Leaves/drug effects , Plant Leaves/growth & development , Plant Leaves/metabolism , Superoxide Dismutase/metabolism
18.
Article in English | MEDLINE | ID: mdl-32679016

ABSTRACT

BACKGROUND: Sulfur-(SM) and nitrogen (NM)-based mustards are the mutagenic incapacitating compounds which are widely used in vesicating the chemical warfare and cause toxicity in many organs, especially skin. SM, as a potent vesicating agent, contributes to the destruction of skin in dermis and epidermis layers. The progression of the lesion depends on the concentration of SM and the duration of exposure. Body responses start with pruritus, erythema, edema and xerosis, which lead to the accumulation of immune cells in the target sites and recruitment of mast cells and paracrine-mediated activity. Pro-inflammatory effectors are accumulated in the epidermis, hair follicles, and sebaceous glands resulting in the destruction of the basement membrane beneath the epidermis. There is still no satisfactory countermeasure against SM-induced lesions in clinical therapy, and the symptomatic or supportive treatments are routine management approaches. OBJECTIVE: The current review highlights the recent progression of herbal medicines application in SM-induced injuries through the illustrative examples and also demonstrates their efficacies, properties and mechanism of actions as therapeutic agents. CONCLUSION: Phytochemicals and herbal extracts with anti-bacterial, anti-inflammatory and antioxidant properties have been recently shown to hold therapeutic promise against the SM-induced cutaneous complications. The present review discusses the possible application of herbal medicines in the healing of SM-induced injuries.


Subject(s)
Mustard Gas/chemistry , Phytochemicals/chemistry , Plant Extracts/chemistry , Plants, Medicinal/chemistry , Sulfur/chemistry , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Gas Scavengers , Herbal Medicine , Humans , Mustard Gas/pharmacology , Nitrogen/chemistry , Nitrogen/pharmacology , Phytochemicals/pharmacology , Plant Extracts/pharmacology , Skin , Sulfur/pharmacology , Wound Healing/drug effects
19.
Bioorg Chem ; 104: 104282, 2020 11.
Article in English | MEDLINE | ID: mdl-33010624

ABSTRACT

Cancer remains considered as one of the leading global health problems either due to meagre and suboptimal therapeutic response of chemotherapeutic agents or due to the emergence of spontaneous complex multidrug resistance in cancer cells. This created a persistent need for the development of new anticancer agents. Enthralled by the high success rate for natural product-based drug discovery and current research scenario, we synthesized a new series of 3,4,5-trimethoxy phenyl ring pendant sulfur-containingcyanopyrimidine derivatives clubbed with different amines intending to search an anticancer lead compound. To probe the anti-proliferative spectrum of the synthesized derivatives, an in-vitro evaluation was piloted against a panel of 60 cancer cell lines at the National Cancer Institute (NCI) representing major types of cancer diseases. Most of the derivatives showed good to moderate anti-proliferative activity. The results revealed that compound 4e displayed the most promising broad-spectrum anticancer activity with high growth inhibition of various cell lines representing multiple cancers diseases. Mechanistic investigation of compound 4e in human breast cancer MDA-MB-231 cells showed that compound 4e triggers cell death through the induction of apoptosis. ADMET studies and reverse screening were also performed to identify the potential targets of designed molecules. It was concluded that 3,4,5-trimethoxy phenyl ring pendant sulfur-containingcyanopyrimidine derivative 4e could act as a promising hit molecule for further development of novel anticancer therapeutics.


Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Pyrimidines/pharmacology , Sulfur/pharmacology , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , Dogs , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Drug Screening Assays, Antitumor , Humans , Madin Darby Canine Kidney Cells/drug effects , Molecular Structure , Pyrimidines/chemical synthesis , Pyrimidines/chemistry , Structure-Activity Relationship , Sulfur/chemistry
20.
J Dairy Sci ; 103(10): 9024-9036, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32773307

ABSTRACT

To test the hypothesis that Cu metabolism in dairy cows is affected by dietary starch concentration and additional sulfur S and Mo, 60 Holstein-Friesian dairy cows that were [mean ± standard error (SE)] 33 ± 2.5 days postcalving and yielding 41 ± 0.9 kg of milk/d were fed 1 of 4 diets in a 2 × 2 factorial design experiment over a 14-wk period. The 4 diets had a Cu concentration of approximately 15 mg/kg of dry matter (DM), a grass silage-to-corn silage ratio of 1:1, a dietary starch concentration of either 150 g/kg of DM (low starch, LS) or 220 g/kg of DM (high starch, HS), and were either unsupplemented (-) or supplemented (+) with an additional 0.8 g of S/kg of DM and 4.4 mg of Mo/kg of DM. We found an effect of dietary starch concentration on mean reticular pH, which was 0.15 pH units lower in cows fed the high starch diets. The addition of S and Mo decreased intake by 1.8 kg of DM/d, an effect that was evident beginning in wk 1 of the study. Mean milk and fat yields were 37.0 and 1.51 kg/d, respectively, and were not affected by dietary treatment. We found an effect of dietary starch concentration on milk protein concentration, protein yield, and urea nitrogen, which were increased by 2.8 g/kg, 0.09 kg/d, and 2.1 mg/dL, respectively, in cows fed the high starch diets. We found no effect of dietary treatment on either cow live weight or body condition. Mean plasma Cu, Fe, and Zn concentrations were 15.3, 42.1, and 14.4 µmol/L, respectively, and were not affected by dietary treatment. In contrast, we found an interaction between dietary starch concentration and Cu antagonists on plasma Mo, where feeding additional S and Mo increased plasma Mo to a greater extent when cows were offered the high versus low starch diet. We also found that increasing dietary starch concentration increased serum ceruloplasmin activity, but serum haptoglobin concentration was not affected by dietary treatment. The addition of S and Mo decreased hepatic Cu concentration, whereas in cows fed the higher dietary starch concentration, hepatic Cu concentration was increased over the period of our study. We concluded that increasing dietary starch concentration decreases rumen pH and increases milk protein yield and hepatic Cu concentration, whereas feeding additional S and Mo decreases intake and hepatic Cu concentration.


Subject(s)
Animal Feed , Cattle , Copper/metabolism , Dietary Carbohydrates/pharmacology , Molybdenum/pharmacology , Rumen/drug effects , Sulfur/pharmacology , Animals , Diet/veterinary , Dietary Carbohydrates/metabolism , Dietary Supplements , Female , Hydrogen-Ion Concentration , Lactation , Liver/drug effects , Liver/metabolism , Milk , Milk Proteins/metabolism , Poaceae/metabolism , Rumen/metabolism , Silage , Sulfur/administration & dosage , Zea mays/metabolism
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