scholarly journals Genotoxic property of poly herbal formulation of annona squomosa, zingiber officinalis and triticum aestivum plant extracts by in vitro chromosomal aberration test

2019 ◽  
Vol 10 (4) ◽  
pp. 3449-3460
Author(s):  
Rajesh R ◽  
Jagadeesh Singh S D ◽  
Channabasava R
Keyword(s):  
Triticum Aestivum ◽  
Chromosomal Aberration ◽  
Metabolic Activation ◽  
Cho Cell ◽  
Cellular Integrity ◽  
Alternative Sources ◽  
Chromosomal Aberration Test ◽  
The One

The present study was aimed to evaluate the genotoxic potential of polyherbal formulations by chromosomal aberration test. Cancer being the second most cause of death among all ailments even after the improvised medications needs alternative sources of treatment. Herbal sources were always among the one as prime treatment sources. Polyherbal formulations were taking the lead in medications because of their broad spectrum of activity and synergic effects. Annona squamosa, Zingiber Officinalis, and Triticum Aestivum formulation with 1:2:3 ratio has shown significant results in the definitive and confirmatory chromosome aberration assays. Indicated the test article PF3 did not induce a statistically significant increase in the percentage of cells with aberrations both in the presence and absence of metabolic activation. PF3 was found non-clostagenic at a maximum dose of 15 µg/ml in the CHO cell line. Inhibition of chromosomal aberration, DNA fragmentation, and maintenance of cellular integrity may prevent the genotoxic effect. Further optimization and in vivo authenticated studies need to be proven.

Studies of the Toxicological Potential of Capsinoids: V. Genotoxicity Studies of Dihydrocapsiate

2008 ◽  
Vol 27 (3_suppl) ◽  
pp. 59-72 ◽  
Author(s):  
Bruce K. Bernard ◽  
Eri Watanabe ◽  
Terutaka Kodama ◽  
Shoji Tsubuku ◽  
Akira Otabe ◽  
...  
Keyword(s):  
Gene Mutation ◽  
Chromosomal Aberration ◽  
Metabolic Activation ◽  
Transgenic Rats ◽  
Negative Results ◽  
Chromosomal Aberration Test ◽  
Mutation Assay ◽  
Gene Mutation Assay

A series of studies was performed to evaluate the safety of dihydrocapsiate (4-hydroxy-3-methoxybenzyl 8-methylnonanoate; CAS no. 205687-03-2). This study evaluated the potential genotoxicity of this compound using a variety of in vitro and in vivo test systems, including bacterial reverse mutation test, chromosomal aberration test, micronucleus test, gene mutation assay with transgenic rats, and single-cell gel (SCG) assay (Comet assay). In vitro tests (bacterial reverse mutation test and chromosomal aberration test) produced positive results in the absence of metabolic activation, but negative results in the presence of metabolic activation. The in vivo gene mutation assay (with transgenic rats) produced negative results, as did the in vivo mouse micronucleus assay, which failed to induce micronucleated polychromatic erythrocytes. Although the rat SCG assay produced statistically significant increases in the Olive tail moment and % tail DNA of the liver and intestine in the 2000 mg/kg group (compared with the negative-control group), a number of factors caused the authors to question the validity of these findings. Taken together, these results suggest that dihydrocapsiate has a low or extremely low likelihood of inducing genotoxicity.

Chromosomal Aberration Test Utilities In Vitro and In Vivo

2014 ◽  
pp. 115-139
Author(s):  
Ana Paula A. Guimarães ◽  
Adriana C. Guimarães ◽  
Diego Á. Alcântara ◽  
Luiz Raimundo Cunha ◽  
Patrícia L. Lima ◽  
...  
Keyword(s):  
Chromosomal Aberration ◽  
Chromosomal Aberration Test

scholarly journals In Vitro Genotoxic Effects of Zerumbone and Cisplatin Combination in CHO Cell Lines

2017 ◽  
Vol 2 (4) ◽  
pp. 101-107
Author(s):  
Adel Sharaf Al-Zubairi
Keyword(s):  
Cell Lines ◽  
Chromosomal Aberrations ◽  
Micronucleus Test ◽  
Metabolic Activation ◽  
Cho Cell ◽  
Genotoxic Effects ◽  
Human Tumour Cells ◽  
Low Concentrations

Objective: Several natural products are being increasingly used in the treatment of cancer to minimize the adverse side effects of cancer chemotherapy. Zerumbone (ZER), the sesquiterpene derived from Zingiber zerumbet Smith, has been reported to have an in vitro anticancer effects against various human tumour cells as well as in vivo against a number of induced malignancies in mice. Previously we have reported the genotoxic effects of ZER in vitro against CHO cell lines. Material and Method: The aim of this study was to investigate the genotoxic effects of the combination of ZER along with cisplatin in CHO cells. Two cytogenetic endpoints were used, namely Chromosomal Aberrations assay (CA) and Micronucleus test (MN). Both cytogenetic endpoints were performed without any metabolic activation. Result: ZER treated cultures showed the significant increase in the frequency of the chromosome aberrations and MN induction. In CA assay, marked changes have been observed after co-treatment of CHO cell lines with different concentration of ZER along with 5 µM Cisplatin when compared to ZER treatment alone, suggesting a possible synergistic genetoxic effects. Whereas, treatment of CHO cell lines with different concentrations of ZER along with 2.5 µM Cisplatin was found to reduce chromosomal aberrations, suggesting an antagonistic genotoxic effect. On the other hand, in MN induction test, co-treatment of CHO cell lines with both 2.5 µM and 5 µM Cisplatin and different concentration of ZER found to reduce the genotoxic effects compared to the 2.5 µM and 5 µM Cisplatin alone suggesting an antagonistic genotoxic effect.Conclusion: The genotoxic effects of combined low concentrations of Cisplatin with different concentrations of ZER could have an antagonist genotoxic potential in vitro in CHO cell lines.

Effect of microbial isolates on microbial yield estimation in RUSITEC system

1998 ◽  
Vol 22 ◽  
pp. 306-308
Author(s):  
M. D. Carro ◽  
E. L. Miller
Keyword(s):  
Protein Synthesis ◽  
Liquid Phase ◽  
Solid Phase ◽  
Liquid Fraction ◽  
Microbial Protein ◽  
Microbial Protein Synthesis ◽  
Continuous Culture System ◽  
The One

The estimation of rumen microbial protein synthesis is one of the main points in the nitrogen (N)-rationing systems for ruminants, as microbial protein provides proportionately 0.4 to 0.9 of amino acids entering the small intestine in ruminants receiving conventional diets (Russell et al., 1992). Methods of estimating microbial protein synthesis rely on marker techniques in which a particular microbial constituent is related to the microbial N content. Marker : N values have generally been established in mixed bacteria isolated from the liquid fraction of rumen digesta and it has been assumed that the same relationship holds in the total population leaving the rumen (Merry and McAllan, 1983). However, several studies have demonstrated differences in composition between solid-associated (SAB) and fluid-associated bacteria in vivo (Legay-Carmier and Bauchart, 1989) and in vitro (Molina Alcaide et al, 1996), as well in marker : N values (Pérez et al., 1996). This problem could be more pronounced in the in vitro semi-continuous culture system RUSITEC, in which there are three well defined components (a free liquid phase, a liquid phase associated with the solid phase and a solid phase), each one having associated microbial populations.The objective of this experiment was to investigate the effect of using different bacterial isolates (BI) on the estimation of microbial production of four different diets in RUSITEC (Czerkawski and Breckenridge, 1977), using (15NH4)2 SO4 as microbial marker, and to assess what effects any differences would have on the comparison of microbial protein synthesis between diets.This study was conducted in conjunction with an in vitro experiment described by Carro and Miller (1997). Two 14-day incubation trials were carried out with the rumen simulation technique RUSITEC (Czerkawski and Breckenridge, 1977). The general incubation procedure was the one described by Czerkawski and Breckenridge (1977) and more details about the procedures of this experiment are given elsewhere (Carro and Miller, 1997).

scholarly journals Evaluation of cytotoxicity and mutagenicity of the benzodiazepine flunitrazepam in vitro and in vivo

2014 ◽  
Vol 50 (2) ◽  
pp. 251-256
Author(s):  
Igor Vivian de Almeida ◽  
Giovana Domingues ◽  
Lilian Capelari Soares ◽  
Elisângela Düsman ◽  
Veronica Elisa Pimenta Vicentini
Keyword(s):  
Rattus Norvegicus ◽  
Bone Marrow Cells ◽  
Micronucleus Test ◽  
Term Treatment ◽  
Genotoxic Effects ◽  
Short Term ◽  
Short Term Treatment ◽  
Chromosomal Aberration Test

Flunitrazepam (FNZ) is a sedative benzodiazepine prescribed for the short-term treatment of insomnia. However, there are concerns regarding possible carcinogenic or genotoxic effects of this medicine. Thus, the aim of this study was to evaluate the cytotoxic, clastogenic and aneugenic effects of FNZ in hepatoma cells from Rattus norvegicus (HTC) in vitro and in bone marrow cells of Wistar rats in vivo. These effects were examined in vitro following treatment with 0.2, 1.0, 5.0 or 10 μg/mL FNZ using a micronucleus test with a cytokinesis block or in vivo using a chromosomal aberration test following treatment with 7, 15 or 30 μg/mL/kg body weight. The results showed that the benzodiazepine concentrations tested were not cytotoxic, aneugenic or clastogenic. However, considering the adverse effects of using this benzodiazepine, more studies are required.

scholarly journals In vitro versus in vivo metabolic activation of mutagens.

1973 ◽  
Vol 6 ◽  
pp. 71-82 ◽  
Author(s):  
H V Malling ◽  
C N Frantz
Keyword(s):  
Metabolic Activation

scholarly journals Microbial enzymes induce colitis by reactivating triclosan in the mouse gastrointestinal tract

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Jianan Zhang ◽  
Morgan E. Walker ◽  
Katherine Z. Sanidad ◽  
Hongna Zhang ◽  
Yanshan Liang ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Molecular Mechanisms ◽  
Ex Vivo ◽  
Metabolic Activation ◽  
Consumer Products ◽  
Environmental Chemicals ◽  
Intestinal Microbes ◽  
Targeted Inhibition

AbstractEmerging research supports that triclosan (TCS), an antimicrobial agent found in thousands of consumer products, exacerbates colitis and colitis-associated colorectal tumorigenesis in animal models. While the intestinal toxicities of TCS require the presence of gut microbiota, the molecular mechanisms involved have not been defined. Here we show that intestinal commensal microbes mediate metabolic activation of TCS in the colon and drive its gut toxicology. Using a range of in vitro, ex vivo, and in vivo approaches, we identify specific microbial β-glucuronidase (GUS) enzymes involved and pinpoint molecular motifs required to metabolically activate TCS in the gut. Finally, we show that targeted inhibition of bacterial GUS enzymes abolishes the colitis-promoting effects of TCS, supporting an essential role of specific microbial proteins in TCS toxicity. Together, our results define a mechanism by which intestinal microbes contribute to the metabolic activation and gut toxicity of TCS, and highlight the importance of considering the contributions of the gut microbiota in evaluating the toxic potential of environmental chemicals.

scholarly journals Type-4 Phosphodiesterase (PDE4) Blockade Reduces NETosis in Cystic Fibrosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Licia Totani ◽  
Concetta Amore ◽  
Antonio Piccoli ◽  
Giuseppe Dell’Elba ◽  
Angelo Di Santo ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Lung Disease ◽  
Pde4 Inhibitor ◽  
Free Dna ◽  
Impaired Lung Function ◽  
Cellular Integrity ◽  
Net Release

Neutrophilic inflammation is a key determinant of cystic fibrosis (CF) lung disease. Neutrophil-derived free DNA, released in the form of extracellular traps (NETs), significantly correlates with impaired lung function in patients with CF, underlying their pathogenetic role in CF lung disease. Thus, specific approaches to control NETosis of neutrophils migrated into the lungs may be clinically relevant in CF. We investigated the efficacy of phosphodiesterase (PDE) type-4 inhibitors, in vitro, on NET release by neutrophils from healthy volunteers and individuals with CF, and in vivo, on NET accumulation and lung inflammation in mice infected with Pseudomonas aeruginosa. PDE4 blockade curbed endotoxin-induced NET production and preserved cellular integrity and apoptosis in neutrophils, from healthy subjects and patients with CF, challenged with endotoxin, in vitro. The pharmacological effects of PDE4 inhibitors were significantly more evident on CF neutrophils. In a mouse model of Pseudomonas aeruginosa chronic infection, aerosol treatment with roflumilast, a selective PDE4 inhibitor, gave a significant reduction in free DNA in the BALF. This was accompanied by reduced citrullination of histone H3 in neutrophils migrated into the airways. Roflumilast-treated mice showed a significant improvement in weight recovery. Our study provides the first evidence that PDE4 blockade controls NETosis in vitro and in vivo, in CF-relevant models. Since selective PDE4 inhibitors have been recently approved for the treatment of COPD and psoriasis, our present results encourage clinical trials to test the efficacy of this class of drugs in CF.

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