scholarly journals The Toxic Mechanism of Gliotoxins and Biosynthetic Strategies for Toxicity Prevention

2021 ◽  
Vol 22 (24) ◽  
pp. 13510
Author(s):  
Wei Ye ◽  
Taomei Liu ◽  
Weiyang Zhang ◽  
Weimin Zhang
Keyword(s):  
Plant Pathogens ◽  
Pythium Ultimum ◽  
Disulfide Bridge ◽  
Signal Pathways ◽  
Ros Production ◽  
Low Doses ◽  
Cytotoxic Effects ◽  
Toxic Mechanism ◽  
Tumor Agent ◽  
Different Doses

Gliotoxin is a kind of epipolythiodioxopiperazine derived from different fungi that is characterized by a disulfide bridge. Gliotoxins can be biosynthesized by a gli gene cluster and regulated by a positive GliZ regulator. Gliotoxins show cytotoxic effects via the suppression the function of macrophage immune function, inflammation, antiangiogenesis, DNA damage by ROS production, peroxide damage by the inhibition of various enzymes, and apoptosis through different signal pathways. In the other hand, gliotoxins can also be beneficial with different doses. Low doses of gliotoxin can be used as an antioxidant, in the diagnosis and treatment of HIV, and as an anti-tumor agent in the future. Gliotoxins have also been used in the control of plant pathogens, including Pythium ultimum and Sclerotinia sclerotiorum. Thus, it is important to elucidate the toxic mechanism of gliotoxins. The toxic mechanism of gliotoxins and biosynthetic strategies to reduce the toxicity of gliotoxins and their producing strains are summarized in this review.

scholarly journals Cytotoxicity studies of Fe 3 O 4 nanoparticles in chicken macrophage cells

2020 ◽  
Vol 7 (4) ◽  
pp. 191561 ◽  
Author(s):  
Shan Zhang ◽  
Shu Wu ◽  
Yiru Shen ◽  
Yunqi Xiao ◽  
Lizeng Gao ◽  
...  
Keyword(s):  
Inflammatory Cytokine ◽  
Cell Activity ◽  
Cytokine Secretion ◽  
Ros Production ◽  
Cytotoxic Effects ◽  
Macrophage Cells ◽  
Cytotoxicity Studies ◽  
Significant Difference ◽  
Chicken Macrophage ◽  
Different Doses

Magnetic Fe 3 O 4 nanoparticles (Fe 3 O 4 -NPs) have been widely investigated for their biomedical applications. The main purpose of this study was to evaluate the cytotoxic effects of different sizes of Fe 3 O 4 -NPs in chicken macrophage cells (HD11). Experimental groups based on three sizes of Fe 3 O 4 -NPs (60, 120 and 250 nm) were created, and the Fe 3 O 4 -NPs were added to the cells at different doses according to the experimental group. The cell activity, oxidative index (malondialdehyde (MDA), superoxide dismutase (SOD) and reactive oxygen species (ROS)), apoptosis and pro-inflammatory cytokine secretion level were detected to analyse the cytotoxic effects of Fe 3 O 4 -NPs of different sizes in HD11 cells. The results revealed that the cell viability of the 60 nm Fe 3 O 4 -NPs group was lower than those of the 120 and 250 nm groups when the same concentration of Fe 3 O 4 -NPs was added. No significant difference in MDA was observed among the three Fe 3 O 4 -NP groups. The SOD level and ROS production of the 60 nm group were significantly greater than those of the 120 and 250 nm groups. Furthermore, the highest levels of apoptosis and pro-inflammatory cytokine secretion were caused by the 60 nm Fe 3 O 4 -NPs. In conclusion, the smaller Fe 3 O 4 -NPs produced stronger cytotoxicity in chicken macrophage cells, and the cytotoxic effects may be related to the oxidative stress and apoptosis induced by increased ROS production as well as the increased expression of pro-inflammatory cytokines.

scholarly journals Effect of 2,4-Diacetylphloroglucinol on Pythium: Cellular Responses and Variation in Sensitivity Among Propagules and Species

2003 ◽  
Vol 93 (8) ◽  
pp. 966-975 ◽  
Author(s):  
Jorge T. de Souza ◽  
Christine Arnould ◽  
Chrystel Deulvot ◽  
Philippe Lemanceau ◽  
Vivienne Gianinazzi-Pearson ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Plant Pathogens ◽  
Pythium Ultimum ◽  
Cellular Responses ◽  
Low Ph ◽  
Cell Content ◽  
Pseudomonas Spp ◽  
Transmission Electron ◽  
First Time ◽  
Resistant Structure

The antibiotic 2,4-diacetylphloroglucinol (2,4-DAPG) plays an important role in the suppression of plant pathogens by several strains of Pseudomonas spp. Based on the results of this study, there is variation within and among Pythium spp. to 2,4-DAPG. Also, various propagules of Pythium ultimum var. sporangiiferum, that are part of the asexual stage of the life cycle, differ considerably in their sensitivity to 2,4-DAPG. Mycelium was the most resistant structure, followed by zoosporangia, zoospore cysts, and zoospores. Additionally, we report for the first time that pH has a significant effect on the activity of 2,4-DAPG, with a higher activity at low pH. Furthermore, the level of acetylation of phloroglucinols is also a major determinant of their activity. Transmission electron microscopy studies revealed that 2,4-DAPG causes different stages of disorganization in hyphal tips of Pythium ultimum var. sporangiiferum, including alteration (proliferation, retraction, and disruption) of the plasma membrane, vacuolization, and cell content disintegration. The implications of these results for the efficacy and consistency of biological control of plant-pathogenic Pythium spp. by 2,4-DAPG-producing Pseudomonas spp. are discussed.

scholarly journals Effect of Soil Physical Conditions on Emission of Allyl Isothiocyanate and Subsequent Microbial Inhibition in Response to Brassicaceae Seed Meal Amendment

Plant Disease ◽  
2019 ◽  
Vol 103 (5) ◽  
pp. 846-852 ◽  
Author(s):  
Likun Wang ◽  
Mark Mazzola
Keyword(s):  
Growth Inhibition ◽  
Soil Water ◽  
Plant Pathogens ◽  
Soil Water Potential ◽  
Allyl Isothiocyanate ◽  
Pythium Ultimum ◽  
Seed Meal ◽  
Soilborne Disease ◽  
Physical Conditions ◽  
Orchard Soils

Generation of allyl isothiocyanate (AITC) in soil treated with residues of specific Brassicaceae species yields direct and indirect suppression of soilborne plant pathogens. Soil physical conditions demonstrably affected the quantity of AITC generated in response to soil incorporation of a Brassica juncea/Sinapis alba seed meal (SM) formulation. The concentration of AITC generated in SM-amended soil increased with an increase in temperature from 10 to 30°C. AITC emission was also elevated with an increase in soil water potential from −1,000 kPa through −40 kPa; however, a significant decrease in AITC emission was observed in a saturated soil environment (0 kPa). Peak AITC emission was obtained 2 to 3 h after SM amendment under optimal conditions but the peak was delayed in soils incubated at low temperature or in extreme moisture environments. Although AITC production varied significantly across different orchard soils, all three orchard soils yielded the same pattern of AITC release in response to SM amendment over the spectrum of soil water potentials examined in this study. Mycelial growth inhibition in fungi and oomycetes isolated from apple roots was dependent on both AITC concentration and exposure time. Pythium ultimum exhibited sensitivity to AITC at concentrations ranging from 0.01 to 0.22 µg g−1 of soil, whereas Hypocrea lixii was insensitive to AITC. Exposure to AITC at a concentration of 0.22 µg g−1 of soil for a period of 2 h restricted hyphal growth of Rhizoctonia solani AG-5, Ilyonectria destructans, and Mortierella alpina. R. solani AG-5 exhibited significant growth inhibition when incubated at AITC concentrations of 0.008 to 0.011 µg g−1 of soil for 10 h. These findings provide information that will be useful in the management of appropriate soil variables to obtain optimal yields of AITC in response to SM soil amendments and indicate that a standard soil moisture prescription may be suitable for use when applying this SM formulation for soilborne disease control.

Effect on the Sensitivity of Lymphoid Cells to Acriflavine after « in vivo » Treatment with Heterologous Albumin Coupled with Diazotized Acriflavin

1966 ◽  
Vol 52 (3) ◽  
pp. 177-185
Author(s):  
Aurelio Di Marco ◽  
Rosella Silvestrini ◽  
Emidio Calendi
Keyword(s):  
Lymph Nodes ◽  
Proliferative Activity ◽  
Lymphoid Cells ◽  
Low Doses ◽  
Proliferating Cells ◽  
In Vivo Treatment ◽  
Albino Mice ◽  
Different Doses

The possibility that the «in vivo» treatment with heterologous albumin coupled with diazotized acriflavine may affect the sensitivity of lymphoid cells to the action of acriflavine was studied. Albino mice CFW strain were treated subcutanceusly with the coupled albumin in the presence of complete Freund adjuvant. Lymph nodes from control and immunized animals, fifteen days after the treament, were cultured «in vitro» in the presence of different doses of acriflavine (from 0.5 to 4 μg/ml). The action of acriflavine was evaluated as the growth of cultures, the percent of lymphoid cells in the different phases of differentiation and the percent of proliferating cells after incubation for 24 hours in the presence of 3H thymidine. Results show that lymphoid cells of immunized mice are less sensitive to the citotoxic activity of acriflavine than those of the controls. Acriflavine, at low doses, reduces the growth of normal cultures and the proliferative activity of immature elements. At the highest doses the proliferation area is almost completely absent and the elements still present are strongly degenerated. Acriflavine, at the concentration able to reduce or to inhibit the growth of control cultures, is ineffective in altering the ratio of immature elements in cultures of immunized animals. The ability of these elements to incorporate 3H thymidine is also unchanged.

scholarly journals Cytotoxic Constituents of the Bark of Hypericum roeperianum towards Multidrug-Resistant Cancer Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Michel-Gael F. Guefack ◽  
Francois Damen ◽  
Armelle T. Mbaveng ◽  
Simplice Beaudelaire Tankeo ◽  
Gabin T. M. Bitchagno ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Colon Adenocarcinoma ◽  
Cancer Cell Lines ◽  
Multidrug Resistant ◽  
Leukemia Cells ◽  
Ros Production ◽  
Cytotoxic Effects ◽  
Induced Apoptosis

The global cancer burden remains a serious concern with the alarming incidence of one in eight men and one in eleven women dying in developing countries. This situation is aggravated by the multidrug resistance (MDR) of cancer cells that hampers chemotherapy. In this study, the cytotoxicity of the methanol extract (HRB), fractions (HRBa, HRBb, and HRBa1-5), and compounds from the bark of Hypericum roeperianum (HRB) was evaluated towards a panel of 9 cancer cell lines. The mode of action of the HRB and trichadonic acid (1) was also studied. Column chromatography was applied to isolate the constituents of HRB. The cytotoxicity of botanicals and phytochemicals was evaluated by the resazurin reduction assay (RRA). Caspase-Glo assay was used to evaluate the activity of caspases, and reactive oxygen species (ROS) (H2DCFH-DA) were assessed by flow cytometry. Phytochemicals isolated from HRB were trichadonic acid (1), fridelan-3-one (2), 2-hydroxy-5-methoxyxanthone (3), norathyriol (4), 1,3,5,6-tetrahydroxyxanthone (5), betulinic acid (6), 3′-hydroxymethyl-2′-(4″-hydroxy-3″,5″-dimethoxyphenyl)-5′,6′:5,6-(6,8-dihydroxyxanthone)-1′,4′-dioxane (7), and 3′-hydroxymethyl-2′-(4″-hydroxy-3″,5″-dimethoxyphenyl)-5′,6′:5,6-(xanthone)-1′,4′-dioxane (8). Botanicals HRB, HRBa, HRBa2-4, HRBb, and doxorubicin displayed cytotoxic effects towards the 9 tested cancer cell lines. The recorded IC50 values ranged from 11.43 µg/mL (against the P-glycoprotein (gp)-overexpressing CEM/ADR5000 leukemia cells) to 26.75 µg/mL (against HCT116 (p53+/+) colon adenocarcinoma cells) for the crude extract HRB. Compounds 1, 5, and doxorubicin displayed cytotoxic effects towards the 9 tested cancer cell lines with IC50 values varying from 14.44 µM (against CCRF-CEM leukemia cells) to 44.20 µM (against the resistant HCT116 (p53−/−) cells) for 1 and from 38.46 µM (against CEM/ADR5000 cells) to 112.27 µM (against the resistant HCT116 (p53−/−) cells) for 5. HRB and compound 1 induced apoptosis in CCRF-CEM cells. The apoptotic process was mediated by enhanced ROS production for HRB or via caspases activation and enhanced ROS production for compound 1. This study demonstrated that Hypericum roeperianum is a potential source of cytotoxic phytochemicals such as trichadonic acid and could be further exploited in cancer chemotherapy.

scholarly journals Potential of Microbial Diversity of Coastal Sand Dunes: Need for Exploration in Odisha Coast of India

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Shubhransu Nayak ◽  
Satyaranjan Behera ◽  
Prasad Kumar Dash
Keyword(s):  
Microbial Diversity ◽  
Mycorrhizal Fungi ◽  
Plant Pathogens ◽  
Sand Dunes ◽  
Organic Matter Content ◽  
Pythium Ultimum ◽  
The State ◽  
Bioactive Metabolites ◽  
Coastal Sand Dunes ◽  
Coastal Sand

Coastal sand dunes are hips and strips formed by sand particles which are eroded and ground rock, derived from terrestrial and oceanic sources. This is considered as a specialized ecosystem characterized by conditions which are hostile for life forms like high salt, low moisture, and low organic matter content. However, dunes are also inhabited by diverse groups of flora, fauna, and microorganisms specifically adapted to these situations. Microbial groups like fungi, bacteria, and actinobacteria are quite abundant in the rhizosphere, phyllosphere, and inside plants which are very much essential for the integration of dunes. Microorganisms in this ecosystem have been found to produce a number of bioactive metabolites which are of great importance to agriculture and industries. Many species of arbuscular mycorrhizal fungi and Rhizobia associated with the roots of dune flora are prolific producers of plant growth promoting biochemicals like indole acetic acid. In addition to that bacteria belonging to Pseudomonas sp., Gammaproteobacteria have been found to have antagonistic activity towards plant pathogens like Rhizoctonia solani, Pythium ultimum, Fusarium oxysporum, and Botrytis cinerea. Many neutrophilic and alkaliphilic eubacterial species, endophytic fungi from dunes have proved their ability for the production of extracellular enzymes like cellulase, pectinase, amylase, protease, tannase, chitinase, etc., which are of great importance to various industries. In this context, it is relevant to observe that the state of Odisha in India has a 480km long coast having numerous sand dunes. These dunes are rich in floral and faunal diversity. However, a comprehensive study is yet to be taken up to explore the microbial diversity and their bioactive potential in this region. The current review sheds light on the enormous potential of sand dune microorganisms in the coast and surfaced the idea and need for such exploration in the state of Odisha, India.

The use of low doses of acepromazine as an aid for lameness diagnosis in horses: An accelerometric evaluation

2015 ◽  
Vol 28 (05) ◽  
pp. 312-317 ◽  
Author(s):  
Gómez Cisneros ◽  
Varela del Arco ◽  
Santiag Llorente ◽  
Santos González ◽  
F. J. López-Sanromán
Keyword(s):  
Clinical Significance ◽  
Stride Length ◽  
Saline Solution ◽  
Gait Pattern ◽  
Stride Frequency ◽  
Low Doses ◽  
Baseline Values ◽  
Different Doses

Summary Objectives: The aim of the present study was to quantify by accelerometry the trotting pattern of adult horses sedated with two different doses of acepromazine, in order to assess the use of this drug in equine lameness evaluations. Methods: Seven mature horses were used and three treatments were administered to each horse: saline solution, acepromazine (0.01 mg/kg), and acepromazine (0.02 mg/ kg). The portable gait analyzer used consisted of three orthogonal accelerometers that measure accelerations along the dorso -ventral, longitudinal, and lateral axes. Baseline values were obtained and after treatment, accelerometric recordings were repeated every five minutes during the first 20 minutes after the injection and then every 10 minutes thereafter for two hours. Ground-tolip distance was also measured. Results: Administration of acepromazine decreased some of the variables investigated and differences between doses were observed. Speed, stride frequency, and stride length were significantly reduced following treatments. For coordination parameters, no significant differences among values were observed. Energetic variables suffered only weak reductions whereas ground-to-lip distance values were significantly decreased up to 120 minutes after treatment. Clinical significance: Acepromazine produces significant alterations in the gait pattern with differences between doses, but it does not affect coordination variables in normal unexcited horses, and at a dose of 0.01 mg/kg may be the tranquilizer of choice for evaluating lameness in this setting.

FURTHER STUDIES ON THYROID - ADRENAL - ASCORBIC ACID RELATIONS IN ANIMALS EXPOSED TO COLD

1956 ◽  
Vol 34 (1) ◽  
pp. 1251-1260 ◽  
Author(s):  
André DesMarais
Keyword(s):  
Ascorbic Acid ◽  
Thyroid Hormones ◽  
Deleterious Effect ◽  
Low Doses ◽  
Growth And Survival ◽  
Beneficial Effects ◽  
Alarm Reaction ◽  
Different Doses ◽  
Adrenalectomized Rats

The effect of ascorbate administration on resistance to cold and thyroid function was studied in adrenalectomized rats receiving various amounts of cortisone and/or DCA; in thyroidectomized rats given different doses of of thyroxine, the effect of ascorbate administration was evaluated on both resistance to cold and adrenal function.In adrenalectomized rats given large doses of cortisone (2.5 mgm.) and exposed to cold, the administration of either ascorbate (150 mgm.) or DCA (2.5 mgm.) enhances the survival, reduces the extent of thymolysis, and decreases the activation of the thyroid. In adrenalectomized rats receiving no cortisone or DCA or low doses (0.4 and 0.1 mgm.) of these hormones, ascorbate administration (150 mgm.) still retains some of its beneficial effects on resistance to cold (better growth and survival); when low doses of DCA (0.1 mgm.) are given without cortisone, ascorbate administration seems to have a deleterious effect on the growth and survival during exposure to cold, with a greater increase in thyroid activity.In thyroidectomized rats exposed to cold, ascorbate administration (150 mgm.) has no effect in the absence of thyroxine, but increases the efficiency of low doses (3 μgm.) of thyroxine, preventing at the same time some of the typical signs of an alarm reaction: thymolysis and adrenal enlargement.These results are interpreted as showing that the role of the cortical hormones in resistance to cold might be limited to a "conditioning" action and that the beneficial effects of ascorbate administration would be mediated through the thyroid hormones.

Effect of 5-Fluorouracil Administered at Low Doses on Cytotoxic Properties of Methotrexate in the in vivo Model of Mice L1210 Leukemia; According to the Schedule of Treatment

Pteridines ◽  
1994 ◽  
Vol 5 (2) ◽  
pp. 55-60
Author(s):  
Julita Graczyk
Keyword(s):  
Survival Time ◽  
Leukemic Cells ◽  
In Vivo Model ◽  
Low Doses ◽  
Simultaneous Administration ◽  
L1210 Leukemia ◽  
Lymphoid Leukemia ◽  
Cytotoxic Effects

Summary The study compared antineoplastic effects of combined methotrexate and 5-fluorouracil therapy on LI210 lymphoid leukemia in mice according to the schedule of treatment. Methotrexate was administered at doses of: LOw.. 0.5 LOw. 5-Fluorouracil was administered at doses of: 0.2 LOIO, 0.1 LOw, 0.02 LOro. The parameters characterizing the efficacy of the therapy were survival time of mice inoculated with LI2l0 leukemic cells .. as well as 1151 excretory capacity of mice inoculated with 1251-iododeoxyuridine-Iabelled leukemic cells. It has been observed that the longest survival time of mice with LI210 leukemia is obtained when methotrexate is administered prior to 5-fluorouracil. Reversing the schedule, or simultaneous administration of the drugs results in shorter survival time. despite the administration of 5-fluorouracil at low doses, ineffective on LI210 leukemia in monotherapy. Cytotoxic effects on LI210 leukemic cells labelled with 1151UDR were present only when methotrexate was administered prior to 5-fluorouracil.

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