scholarly journals Examination of some toxicological parameters of dimethylamylamine when consumed alone or with caffeine

2020 ◽  
Vol 72 (3) ◽  
pp. 413-423
Author(s):  
Adem Güner ◽  
Hasan Türkez
Keyword(s):  
Membrane Damage ◽  
Chorioallantoic Membrane ◽  
Dependent Manner ◽  
Genotoxic Effects ◽  
Cytotoxic Effects ◽  
Cell Membrane Damage ◽  
Lactate Dehydrogenase Release ◽  
Total Antioxidant ◽  
Total Oxidative Status ◽  
First Time

Dimethylamylamine (DMAA) is a bodybuilding supplement with fat-burner or performance-enhancing properties. DMAA is often combined with caffeine to enhance its effectiveness and this can have serious adverse effects on health. In this study, we examined for the first time the cytotoxic, oxidative and genotoxic effects of DMAA in the presence or absence of caffeine in lymphocytes cultured from human blood, and its vascular irritant effects in a hen's chorioallantoic membrane egg test. Cytotoxic effects were observed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT), lactate dehydrogenase release (LDH), which serves as a measure of cell membrane damage, changes in the mitotic index (MI) and proliferative rate index (PRI) assays. Oxidative changes were evaluated by the total antioxidant activity and the total oxidative status assay. Genotoxic damage was analyzed by chromosomal aberration and micronucleus assays. DMAA and its combination with caffeine (cDMAA) had no genotoxic effects. DMAA (1000 mg/L) and cDMAA (500 and 1000 mg/L) decreased cell viability while significantly increasing LDH activity, MI and the oxidative level. DMAA and cDMAA caused weak and moderate vascular irritant effects, respectively. In conclusion, DMAA exhibits cytotoxic effects via membrane dysfunction and mitotic disturbance following increased oxidative stress in a dose- and caffeine-dependent manner.

scholarly journals Cytotoxic activity of the aqueous extract of Micromeria fruticosa (L.) Druce subsp. serpyllifolia on human U-87 MG cell lines

2017 ◽  
Vol 69 (3) ◽  
pp. 449-453 ◽  
Author(s):  
Kubra Koc ◽  
Ozlem Ozdemir ◽  
Faruk Kizilkaya ◽  
Meryem Sengul ◽  
Hasan Turkez
Keyword(s):  
Aqueous Extract ◽  
Membrane Damage ◽  
Folk Medicine ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Cell Membrane Damage ◽  
Human Glioblastoma Multiforme ◽  
Total Antioxidant ◽  
High Concentrations ◽  
Micromeria Fruticosa

Micromeria fruticosa (L.) Druce subsp. serpyllifolia, which is widely used in folk medicine as a medicinal herbal tea, is grown in different areas of Turkey and the Mediterranean region. The present study was conducted to evaluate the aqueous extract of Micromeria fruticosa subsp. serpyllifolia for its antioxidant and antiproliferative activity on a human glioblastoma multiforme cell line (U-87 MG), which has not been reported before. Here, the extract was added to cultures at 8 different concentrations (0-200 ?g/mL). Cell viability and cell membrane damage was determined using the MTT and LDH assays for 48 h, respectively. To examine the oxidative effects, total antioxidant capacity (TAC) and total oxidant status (TOS) levels were measured. The extract displayed considerable antiproliferative activities at the high concentrations of 175 and 200 ?g/mL. Furthermore, the extract caused a significant increase in the release of the lactate dehydrogenase (LDH) enzyme in a concentration-dependent manner; 200 ?g/mL of extract enhanced the release of LDH. Treatments with extract at higher doses increased TOS levels and decreased TAC levels in human U-87 MG cells. Our study suggests that the aqueous extract of Micromeria fruticosa ssp. serpyllifolia was capable of inducing growth inhibition of cancer cells. These results encourage further research to assess the value of the extract in modern phytotherapy.

scholarly journals In vitro risk assessment of Padina pavonica (Linnaeus) (Brown algae)

2021 ◽  
Vol 7 (1) ◽  
pp. 31-38
Author(s):  
Adem Güner
Keyword(s):  
Brown Algae ◽  
Antioxidant Properties ◽  
Water Extract ◽  
Sister Chromatid Exchanges ◽  
Genotoxic Effects ◽  
Anticancer Effects ◽  
Low Concentrations ◽  
Total Antioxidant ◽  
Total Oxidative Status

Padina pavonica (Linnaeus) Thivy 1960 is a brown algae that is antioxidant, antimicrobial, and anticancer effects and is generally used in soup, salad, and other dishes. However, no studies have been reported on safe consumption in humans to date. For this purpose, this study was conducted to determine the cytotoxic and genotoxic effects of P. pavonica on lymphocytes cultured from human blood. The water extract of P. pavonica was added into culture tubes at various concentrations (0.5-1000 μg/mL). Cytotoxic effects were determined by MTT assay. Antioxidant/oxidant status was evaluated by total antioxidant capacity (TAC) and total oxidative status (TOS) assays. Genotoxic effects were investigated by sister chromatid exchanges and micronucleus assays. Our results showed that P. pavonica had no genotoxic effects, even at higher concentrations. 1000 μg/mL concentration of P. pavonica caused an increase (P<0.05) TOS levels while significantly reducing cell viability. However, low concentrations (50 and 100 μg/mL) significantly increased (P<0.05) TAC levels. In conclusion, P. pavonica can be safely consumed with its non-genotoxic and antioxidant properties in a manner dose-dependent.

scholarly journals A New CYP2E1 Inhibitor, 12-Imidazolyl-1-dodecanol, Represents a Potential Treatment for Hepatocellular Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Torsten Diesinger ◽  
Alfred Lautwein ◽  
Sebastian Bergler ◽  
Dominik Buckert ◽  
Christian Renz ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Chorioallantoic Membrane ◽  
Simultaneous Increase ◽  
Dependent Manner ◽  
Antitumour Effect ◽  
Proliferating Cells ◽  
Nonalcoholic Fatty Liver ◽  
Cycle Regulation ◽  
First Time

Cytochrome P450 2E1 (CYP2E1) is a key target protein in the development of alcoholic and nonalcoholic fatty liver disease (FLD). The pathophysiological correlate is the massive production of reactive oxygen species. The role of CYP2E1 in the development of hepatocellular carcinoma (HCC), the final complication of FLD, remains controversial. Specifically, CYP2E1 has not yet been defined as a molecular target for HCC therapy. In addition, a CYP2E1-specific drug has not been developed. We have already shown that our newly developed CYP2E1 inhibitor 12-imidazolyl-1-dodecanol (I-ol) was therapeutically effective against alcoholic and nonalcoholic steatohepatitis. In this study, we investigated the effect of I-ol on HCC tumorigenesis and whether I-ol could serve as a possible treatment option for terminal-stage FLD. I-ol exerted a very highly significant antitumour effect against hepatocellular HepG2 cells. Cell viability was reduced in a dose-dependent manner, with only the highest doses causing a cytotoxic effect associated with caspase 3/7 activation. Comparable results were obtained for the model colorectal adenocarcinoma cell line, DLD-1, whose tumorigenesis is also associated with CYP2E1. Transcriptome analyses showed a clear effect of I-ol on apoptosis and cell-cycle regulation, with the increased expression of p27Kip1 being particularly noticeable. These observations were confirmed at the protein level for HepG2 and DLD-1 cells grafted on a chorioallantoic membrane. Cell-cycle analysis showed a complete loss of proliferating cells with a simultaneous increase in S-phase arrest beginning at a threshold dose of 30 μM. I-ol also reduced xenograft tumour growth in nude mice. This antitumour effect was not associated with tumour cachexia. I-ol was not toxic to healthy tissues or organs. This study demonstrates for the first time the therapeutic effect of the specific CYP2E1 inhibitor I-ol on the tumorigenesis of HCC. Our findings imply that I-ol can potentially be applied therapeutically on patients at the final stage of FLD.

scholarly journals Amination of Graphene Oxide Leads to Increased Cytotoxicity in Hepatocellular Carcinoma Cells

2020 ◽  
Vol 21 (7) ◽  
pp. 2427 ◽  
Author(s):  
Milena Georgieva ◽  
Bela Vasileva ◽  
Giorgio Speranza ◽  
Dayong Wang ◽  
Kalin Stoyanov ◽  
...  
Keyword(s):  
Graphene Oxide ◽  
Cell Membrane ◽  
Cancer Cells ◽  
Biological Activities ◽  
Membrane Damage ◽  
Hepatocellular Cancer ◽  
Pristine Graphene ◽  
Hepatic Cancer ◽  
Dependent Manner ◽  
Cell Membrane Damage

Clinically, there is an urgent need to identify new therapeutic strategies for selectively treating cancer cells. One of the directions in this research is the development of biocompatible therapeutics that selectively target cancer cells. Here, we show that novel aminated graphene oxide (haGO-NH2) nanoparticles demonstrate increased toxicity towards human hepatocellular cancer cells compared to pristine graphene oxide(GO). The applied novel strategy for amination leads to a decrease in the size of haGO-NH2 and their zeta potential, thus, assuring easier penetration through the cell membrane. After characterization of the biological activities of pristine and aminated GO, we have demonstrated strong cytotoxicity of haGO-NH2 toward hepatic cancer cells—HepG2 cell line, in a dose-dependent manner. We have presented evidence that the cytotoxic effects of haGO-NH2 on hepatic cancer cells were due to cell membrane damage, mitochondrial dysfunction and increased reactive oxygen species (ROS) production. Intrinsically, our current study provides new rationale for exploiting aminated graphene oxide as an anticancer therapeutic.

Cytotoxic Effects of a Novel Thialo Benzene Derivative 2,4-Dithiophenoxy-1-iodo-4-bromobenzene (C18H12S2IBr) in L929 Cells

2014 ◽  
Vol 33 (4) ◽  
pp. 319-324 ◽  
Author(s):  
Aysun Kılıç Süloğlu ◽  
Elif Karacaoğlu ◽  
Evrim Arzu Koçkaya ◽  
Güldeniz Selmanoğlu ◽  
Elif Loğoglu
Keyword(s):  
Metabolic Activity ◽  
Antifungal Agent ◽  
Membrane Damage ◽  
Good Alternative ◽  
Enzyme Linked Immunosorbent Assay ◽  
Benzene Derivative ◽  
Cytotoxic Effects ◽  
L929 Cells ◽  
Cell Membrane Damage ◽  
Diphenyl Tetrazolium Bromide

The aim of this study was to compare the cytotoxic effects of a newly synthesized thialo benzene derivative 2,4-dithiophenoxy-1-iodo-4-bromobenzene (C18H12S2IBr) and a well-known antifungal agent, fluconazole, in L929 cells. L929 cells were treated with 250, 500, or 1000 µg/mL of C18H12S2IBr and with the same doses of fluconazole. Cytotoxicity tests including 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), lactate dehydrogenase (LDH) leakage, and protein content were compared. Glucose and lactate concentrations were measured to determine alterations in metabolic activity. Apoptosis was investigated by TUNEL test and results were supported with survivin enzyme-linked immunosorbent assay. Treatment with C18H12S2IBr resulted in a concentration-dependent cytotoxicity as indicated by MTT, LDH leakage assay, and decreased protein concentration. The loss of cell viability and the increased LDH leakage in 500 µg/mL and 1000 µg/mL C18H12S2IBr and fluconazole groups indicated cell membrane damage and necrotic cell death. In all groups, metabolic activities were altered but apoptosis was not induced. We have previously investigated lower doses of C18H12S2IBr; there was no cytotoxicity in L929 cells. In this study, higher doses caused cytotoxicity and alterations in metabolic activity . When we consider the similar results obtained from fluconazole and especially the lowest dose of C18H12S2IBr, this newly synthesized compound may be a good alternative antifungal agent.

Cytotoxic and cytogenetic effects of α-copaene on rat neuron and N2a neuroblastoma cell lines

Biologia ◽  
2014 ◽  
Vol 69 (7) ◽  
Author(s):  
Hasan Turkez ◽  
Basak Togar ◽  
Abdulgani Tatar ◽  
Fatime Geyıkoglu ◽  
Ahmet Hacımuftuoglu
Keyword(s):  
Cell Lines ◽  
Cell Cultures ◽  
Neuroblastoma Cell ◽  
Medicinal And Aromatic Plants ◽  
Damage Potential ◽  
Total Antioxidant ◽  
Total Oxidative Status ◽  
Oxidative Effects ◽  
First Time

AbstractAlpha-copaene (α-COP), a tricyclic sesquiterpene, is present in several essential oils of medicinal and aromatic plants and has antioxidant and antigenotoxic features. Its cytotoxic, cytogenetic and oxidative effects have not been investigated in neuron and N2a neuroblastoma (NB) cell cultures. Therefore, we aimed to describe in vitro: (i) cytotoxic properties by 3-(4,5-dimetylthiazol-2-yl)-2,5-diphenlytetrazolium bromide test; (ii) antioxidant/oxidant activity by total antioxidant capacity (TAC) and total oxidative status (TOS) analysis; and (iii) genotoxic damage potential by single cell gel electrophoresis — of α-COP in healthy neuron and N2a-NB cell cultures for the first time. Significant (P < 0.05) decrease in cell proliferation were observed in cultured primary rat neurons starting with the concentration of 150 mg/L and in N2a-NB cells starting with 100 mg/L. In addition, 25 mg/L of α-COP treatment caused increase of TAC levels and α-COP treatments at higher doses led to increase of TOS levels in neuron N2a-NB cell cultures. Moreover, none of the tested concentrations of α-COP have shown a genotoxic effect on both cell lines. Our findings clearly demonstrate that α-COP exhibited mild cytotoxic effects on N2a-NB cell line. In conclusion, α-COP may have potential as an anticancer agent, which needs to be further studied.

scholarly journals A Tool Derived from the Vicia faba Micronucleus Assay, to Assess Genotoxicity, Cytotoxicity or Biostimulation of Novel Compounds Used in Agriculture

Agronomy ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 321
Author(s):  
Perrine Klein ◽  
Lorelei Chauvey ◽  
Jean Kallerhoff ◽  
Eric Pinelli ◽  
Marie Morard ◽  
...  
Keyword(s):  
Vicia Faba ◽  
Maleic Hydrazide ◽  
Lead Nitrate ◽  
Micronucleus Assay ◽  
Growth Potential ◽  
Protective Effects ◽  
Genotoxic Effects ◽  
Cytotoxic Effects ◽  
Conventional Agriculture ◽  
Rapid Tests

The increased use of biostimulants in conventional agriculture and organic farming requires the implementation of rapid tests to determine their effectiveness in enhancing plant growth and protection against abiotic stresses. However, their innocuity to plant health has rarely been demonstrated. We used the Vicia faba Micronucleus Assay, as described by the standard AFNOR EN ISO 29200(2020-05) to reveal biostimulant, genotoxic and cytotoxic effects of four commercialized wood-based products by comparing mitotic indices and micronucleus frequencies with respect to the controls. Neither genotoxicity, as measured by micronucleus frequency (MN), nor cytotoxicity, assessed by Mitotic index counts, was observed. Additionally, one of these stimulants (BHS®) conferred protective effects against contaminants (maleic hydrazide or lead nitrate). We describe that plotting micronuclei frequency against mitotic indices allows discrimination between cytotoxic/genotoxic effects from growth levels. Vicia faba experiments were successfully transposed to other agronomical important crops such as corn and sunflower. This technique can be valuable to industrials, to assess growth, potential cytoxicity and genotoxicity effects of any new biostimulant or organic.

scholarly journals NF-κB and FosB mediate inflammation and oxidative stress in the blast lung injury of rats exposed to shock waves

2021 ◽  
Author(s):  
Hong Wang ◽  
Wenjuan Zhang ◽  
Jinren Liu ◽  
Junhong Gao ◽  
Le Fang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lung Injury ◽  
Shock Waves ◽  
Time Dependent ◽  
Inflammatory Factors ◽  
Control Group ◽  
Dependent Manner ◽  
Total Antioxidant ◽  
Blast Lung Injury ◽  
And Oxidative Stress

Abstract Blast lung injury (BLI) is the major cause of death in explosion-derived shock waves; however, the mechanisms of BLI are not well understood. To identify the time-dependent manner of BLI, a model of lung injury of rats induced by shock waves was established by a fuel air explosive. The model was evaluated by hematoxylin and eosin staining and pathological score. The inflammation and oxidative stress of lung injury were also investigated. The pathological scores of rats’ lung injury at 2 h, 24 h, 3 days, and 7 days post-blast were 9.75±2.96, 13.00±1.85, 8.50±1.51, and 4.00±1.41, respectively, which were significantly increased compared with those in the control group (1.13±0.64; P&lt;0.05). The respiratory frequency and pause were increased significantly, while minute expiratory volume, inspiratory time, and inspiratory peak flow rate were decreased in a time-dependent manner at 2 and 24 h post-blast compared with those in the control group. In addition, the expressions of inflammatory factors such as interleukin (IL)-6, IL-8, FosB, and NF-κB were increased significantly at 2 h and peaked at 24 h, which gradually decreased after 3 days and returned to normal in 2 weeks. The levels of total antioxidant capacity, total superoxide dismutase, and glutathione peroxidase were significantly decreased 24 h after the shock wave blast. Conversely, the malondialdehyde level reached the peak at 24 h. These results indicated that inflammatory and oxidative stress induced by shock waves changed significantly in a time-dependent manner, which may be the important factors and novel therapeutic targets for the treatment of BLI.

scholarly journals Secreted KIAA1199 promotes the progression of rheumatoid arthritis by mediating hyaluronic acid degradation in an ANXA1-dependent manner

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Wei Zhang ◽  
Guoyu Yin ◽  
Heping Zhao ◽  
Hanzhi Ling ◽  
Zhen Xie ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Hyaluronic Acid ◽  
Dependent Manner ◽  
Collagen Induced Arthritis ◽  
Intracellular Degradation ◽  
Main Pathway ◽  
First Time

AbstractIn inflamed joints, enhanced hyaluronic acid (HA) degradation is closely related to the pathogenesis of rheumatoid arthritis (RA). KIAA1199 has been identified as a hyaladherin that mediates the intracellular degradation of HA, but its extracellular function remains unclear. In this study, we found that the serum and synovial levels of secreted KIAA1199 (sKIAA1199) and low-molecular-weight HA (LMW-HA, MW < 100 kDa) in RA patients were significantly increased, and the positive correlation between them was shown for the first time. Of note, treatment with anti-KIAA1199 mAb effectively alleviated the severity of arthritis and reduced serum LMW-HA levels and cytokine secretion in collagen-induced arthritis (CIA) mice. In vitro, sKIAA1199 was shown to mediate exogenous HA degradation by attaching to the cell membrane of RA fibroblast-like synoviosytes (RA FLS). Furthermore, the HA-degrading activity of sKIAA1199 depended largely on its adhesion to the membrane, which was achieved by its G8 domain binding to ANXA1. In vivo, kiaa1199-KO mice exhibited greater resistance to collagen-induced arthritis. Interestingly, this resistance could be partially reversed by intra-articular injection of vectors encoding full-length KIAA1199 instead of G8-deleted KIAA119 mutant, which further confirmed the indispensable role of G8 domain in KIAA1199 involvement in RA pathological processes. Mechanically, the activation of NF-κB by interleukin-6 (IL-6) through PI3K/Akt signaling is suggested to be the main pathway to induce KIAA1199 expression in RA FLS. In conclusion, our study supported the contribution of sKIAA1199 to RA pathogenesis, providing a new therapeutic target for RA by blocking sKIAA1199-mediated HA degradation.

scholarly journals Brassinolide Enhances the Level of Brassinosteroids, Protein, Pigments, and Monosaccharides in Wolffia arrhiza Treated with Brassinazole

Plants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1311
Author(s):  
Magdalena Chmur ◽  
Andrzej Bajguz
Keyword(s):  
Plant Growth ◽  
Growth And Development ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Plant Growth And Development ◽  
Concentration Dependent Manner ◽  
Spectrophotometric Methods ◽  
Synthetic Inhibitor ◽  
Wolffia Arrhiza ◽  
First Time

Brassinolide (BL) represents brassinosteroids (BRs)—a group of phytohormones that are essential for plant growth and development. Brassinazole (Brz) is as a synthetic inhibitor of BRs’ biosynthesis. In the present study, the responses of Wolffia arrhiza to the treatment with BL, Brz, and the combination of BL with Brz were analyzed. The analysis of BRs and Brz was performed using LC-MS/MS. The photosynthetic pigments (chlorophylls, carotenes, and xanthophylls) levels were determined using HPLC, but protein and monosaccharides level using spectrophotometric methods. The obtained results indicated that BL and Brz influence W. arrhiza cultures in a concentration-dependent manner. The most stimulatory effects on the growth, level of BRs (BL, 24-epibrassinolide, 28-homobrassinolide, 28-norbrassinolide, catasterone, castasterone, 24-epicastasterone, typhasterol, and 6-deoxytyphasterol), and the content of pigments, protein, and monosaccharides, were observed in plants treated with 0.1 µM BL. Whereas the application of 1 µM and 10 µM Brz caused a significant decrease in duckweed weight and level of targeted compounds. Application of BL caused the mitigation of the Brz inhibitory effect and enhanced the BR level in duckweed treated with Brz. The level of BRs was reported for the first time in duckweed treated with BL and/or Brz.

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