Cr and Ni simultaneous phytotoxicity and mutagenicity assay

For genotoxicity study simultaneous phytotoxicity and mutagenicity assay with Vicia sativa L. var. Klára was used. For phytotoxicity the following rank orders of growth inhibition can be arranged: for roots: Ni(II) > Cr(VI) > Cr(III); for shoots: Ni(II) > Cr(VI) ≥ Cr (III). For mutagenicity assay root tips of V. sativa were used and chromosome aberrations were determined at least in 500-anatelophases. All tested metals exerted in V. sativa a significant increase of chromosomal aberration rate in applied concentrations. Maximum of aberrations invoked Cr(VI) and the rank order of aberrations fall was: Cr(VI) > Ni(II) > Cr(III). Genotoxic effects of metals were determined by analysis of micronuclei frequency in the pollen tetrads of Tradescantia plants. None of tested metal significantly stimulated micronuclei frequency and genotoxic effect was decreased in order: Cr(VI) ≥ Ni(II) > Cr(III).

A Comparison of Nine Machine Learning Mutagenicity Models and Their Application for Predicting Pyrrolizidine Alkaloids

Random forest, support vector machine, logistic regression, neural networks and k-nearest neighbor (lazar) algorithms, were applied to a new Salmonella mutagenicity dataset with 8,290 unique chemical structures utilizing MolPrint2D and Chemistry Development Kit (CDK) descriptors. Crossvalidation accuracies of all investigated models ranged from 80 to 85% which is comparable with the interlaboratory variability of the Salmonella mutagenicity assay. Pyrrolizidine alkaloid predictions showed a clear distinction between chemical groups, where otonecines had the highest proportion of positive mutagenicity predictions and monoesters the lowest.

Antioxidant, biofilm inhibition and mutagenic activities of newly substituted fibrates

Purpose: A series of benzylidene-2-(4-bromophenoxy)-2-methyl propane hydrazides (1-10) were synthesized and assay them for their biofilm inhibition, antioxidant and mutagenic. Methods: All derivatives were prepared by condensation of various substituted benzaldehyde and acetophenones with 2-(4-bromorophenoxy)-2-methyl propane hydrazide, which was itself prepared by hydrazinolysis of ethyl-2-(4-bromophenoxy)-2-methyl propanoate and were characterized by FTIR, 1H NMR 13C NMR, mass spectrometry. They were screened for their in-vitro anti-oxidant, biofilm inhibition and mutagenicity by established methods. Results: Anti-oxidant results revealed that the electron donating group enhanced the scavenging ability of the compounds as seen in compounds 4b, 4h and 4i. In biofilm inhibition studies, all compounds were more active against Gram –ive bacterial strain when compared to gram +ive strain. The mutagenicity assay results indicate that the compound having chloro group substitution is mutagenic. Conclusion: The benzylidine compounds of 2-(4-bromophenoxy)-2-methyl hydrazide possessing electron donating substituents exhibit superior activities to the electron withdrawing group substituents.

Anti-biofilm Potential of Elletaria cardamomum Essential Oil Against Escherichia coli O157:H7 and Salmonella Typhimurium JSG 1748

Foodborne pathogens, microbial recurrent infections, and antibiotic resistance have driven researchers to explore natural compounds as safe alternative antimicrobials. In this study, the chemical profile, antimicrobial, and mutagenic activities of the Elletaria cardamomum essential oil were investigated. GC-MS analysis identified the major bioactive components as α-terpinyl acetate, 1,8-cineole, linalool acetate, and sabinene, at concentrations of 34.95, 25.30, 8.13, and 5.48% respectively, of the essential oil’s content. Regarding antimicrobial activity, the minimum inhibitory concentration of green cardamom essential oil was 1% against Escherichia coli O157:H7 and Pseudomonas aeruginosa ATCC 14213. Green cardamom essential oil, when used at concentrations of 0.015, 0.031, 0.062, and 0.125% (v/v) prevented biofilm formation of Escherichia coli O157:H7 by 64.29, 65.98, 70.41, and 85.59%, respectively. Furthermore, these concentrations inhibited 6.13, 45.50, 49.45, and 100%, respectively, of the Salmonella Typhimurium JSG 1748 biofilm. A mutagenicity assay confirmed that green cardamom essential oil has no demonstrable mutagenic activity against the tested strains. The study’s findings suggest that green cardamom derived bioactive compounds are safe organic antimicrobials, effective in controlling biofilm formation by Gram-negative pathogens. Moreover, such compounds could possibly be used in the food industry (e.g., bakery, dairy, meat, and other food products) as a safe alternative to chemical preservatives (antimicrobials) to enhance shelf life by improving the antimicrobial status while at the same time imparting a pleasant and appealing aroma for consumers.

In vitro mutagenicity of selected environmental carcinogens and their metabolites in MutaMouse FE1 lung epithelial cells

Chemicals in commerce or under development must be assessed for genotoxicity; assessment is generally conducted using validated assays (e.g. Tk mouse lymphoma assay) as part of a regulatory process. Currently, the MutaMouse FE1 cell mutagenicity assay is undergoing validation for eventual use as a standard in vitro mammalian mutagenicity assay. FE1 cells have been shown to be metabolically competent with respect to some cytochrome P450 (CYP) isozymes; for instance, they can convert the human carcinogen benzo[a]pyrene into its proximate mutagenic metabolite. However, some contradictory results have been noted for other genotoxic carcinogens that require two-step metabolic activation (e.g. 2-acetylaminofluorene and 2-amino-3-methylimidazo[4,5-f]quinoxaline). Here, we examined three known or suspected human carcinogens, namely acrylamide, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 4-aminobiphenyl (4-ABP), together with their proximate metabolites (i.e. glycidamide, N-OH-PhIP and N-OH-4-ABP), to aid in the validation of the FE1 cell mutagenicity assay. Assessments of the parent compounds were conducted both in the presence and absence of an exogenous metabolic activation mixture S9; assessments of the metabolites were in the absence of S9. The most potent compound was N-OH-PhIP -S9, which elicited a mutant frequency (MF) level 5.3-fold over background at 5 µM. There was a 4.3-fold increase for PhIP +S9 at 5 µM, a 1.7-fold increase for glycidamide −S9 at 3.5 mM and a 1.5-fold increase for acrylamide +S9 at 4 mM. Acrylamide −S9 elicited a marginal 1.4-fold MF increase at 8 mM. Treatment with PhIP −S9, 4-ABP ±S9 and N-OH-4-ABP −S9 failed to elicit significant increases in lacZ MF with any of the treatment conditions tested. Gene expression of key CYP isozymes was quantified by RT-qPCR. Cyp1a1, 1a2 and 1b1 are required to metabolise PhIP and 4-ABP. Results showed that treatment with both compounds induced expression of Cyp1a1 and Cyp1b1 but not Cyp1a2. Cyp2e1, which catalyses the bioactivation of acrylamide to glycidamide, was not induced after acrylamide treatment. Overall, our results confirm that the FE1 cell mutagenicity assay has the potential for use alongside other, more traditional in vitro mutagenicity assays.

Interaction of Thalassia testudinum Metabolites with Cytochrome P450 Enzymes and Its Effects on Benzo(a)pyrene-Induced Mutagenicity

The aim of the present work was to evaluate the effects of Thalassia testudinum hydroethanolic extract, its polyphenolic fraction and thalassiolin B on the activity of phase I metabolizing enzymes as well as their antimutagenic effects. Spectrofluorometric techniques were used to evaluate the effect of tested products on rat and human CYP1A and CYP2B activity. The antimutagenic effect of tested products was evaluated in benzo[a]pyrene (BP)-induced mutagenicity assay by an Ames test. Finally, the antimutagenic effect of Thalassia testudinum (100 mg/kg) was assessed in BP-induced mutagenesis in mice. The tested products significantly (p < 0.05) inhibit rat CYP1A1 activity, acting as mixed-type inhibitors of rat CYP1A1 (Ki = 54.16 ± 9.09 μg/mL, 5.96 ± 1.55 μg/mL and 3.05 ± 0.89 μg/mL, respectively). Inhibition of human CYP1A1 was also observed (Ki = 197.1 ± 63.40 μg/mL and 203.10 ± 17.29 μg/mL for the polyphenolic fraction and for thalassiolin B, respectively). In addition, the evaluated products significantly inhibit (p < 0.05) BP-induced mutagenicity in vitro. Furthermore, oral doses of Thalassia testudinum (100 mg/kg) significantly reduced (p < 0.05) the BP-induced micronuclei and oxidative damage, together with an increase of reduced glutathione, in mice. In summary, Thalassia testudinum metabolites exhibit antigenotoxic activity mediated, at least, by the inhibition of CYP1A1-mediated BP biotransformation, arresting the oxidative and mutagenic damage. Thus, the metabolites of T. testudinum may represent a potential source of chemopreventive compounds for the adjuvant therapy of cancer.

Interaction of Thalassia testudinum Metabolites with Cytochrome P450 Enzymes and Its Effects on Benzo(a)pyrene-Induced Mutagenicity

The aim of the present work was to evaluate the effects of Thalassia testudinum hydroethanolic extract, its polyphenolic fraction, and thalassiolin B on the activity of phase I metabolizing enzymes as well as their antimutagenic effects. Spectrofluorometric techniques were used to evaluate the effect of tested products on rat and human CYP1A and CYP2B activity. The antimutagenic effect of tested products was evaluated in benzo[a]pyrene (BP)-induced mutagenicity assay by Ames test. Finally, the antimutagenic effect of Thalassia testudinum (100 mg/kg) was assessed in a BP-induced mutagenesis in mice. The tested products significantly (p&lt;0.05) inhibit rat CYP1A1 activity, acting as mixed-type inhibitors of rat CYP1A1 (Ki = 54.16&plusmn;9.09 &mu;g/mL, 5.96&plusmn;1.55 &mu;g/mL and 3.05&plusmn;0.89 &mu;g/mL, respectively). Inhibition of human CYP1A1 was also observed (Ki = 197.1&plusmn;63.40 &mu;g/mL and 203.10&plusmn;17.29 &mu;g/mL for the polyphenolic fraction and for thalassiolin B, respectively). In addition, the evaluated products significantly inhibit (p&lt;0.05) benzo[a]pyrene (BP)-induced mutagenicity in vitro. Furthermore, oral doses of Thalassia testudinum (100 mg/kg) significantly reduced (p&lt;0.05) the BP-induced micronuclei and oxidative damage, together with an increase of glutathione, in mice. In summary, Thalassia testudinum metabolites exhibit antigenotoxic activity mediated, at least, by the inhibition of CYP1A1-mediated BP biotransformation. Thus, the metabolites of T. testudinum may represent a potential source of chemopreventive compounds for adjuvant therapy of cancer.

Comparative Mutagenic Potential of Anti-Influenza Drugs using AMES Salmonella / Microsome mutagenicity Assay

.