The targeted compounds in this research, resveratrol analogs 1-14, were synthesized as mixtures of isomers by the Wittig reaction using heterocyclic triphenylphosphonium salts and various benzaldehydes. The planned compounds were those possessing the trans-configuration as the biologically active trans-resveratrol. The pure isomers were obtained by repeated column chromatography in various isolated yields depending on the heteroaromatic ring. It was found that butyrylcholinesterase (BChE) was more sensitive to the heteroaromatic resveratrol analogs than acetylcholinesterase (AChE), except for 6, the methylated thiophene derivative with chlorine, which showed equal inhibition toward both enzymes. Compounds 5 and 8 achieved the highest BChE inhibition with IC50 values of 22.9 and 24.8 μM, respectively. The same as with AChE and BChE, methylated thiophene subunits of resveratrol analogs showed better enzyme inhibition than unmethylated ones. Two antioxidant spectrophotometric methods, DPPH and CUPRAC, were applied to determine the antioxidant potential of new heteroaromatic resveratrol analogs. The molecular docking of these compounds was conducted to visualize the ligand-active site complexes\' structure and identify the non-covalent interactions responsible for the complex\'s stability, which influence the inhibitory potential. As ADME properties are crucial in developing drug product formulations, they have also been addressed in this work. The potential genotoxicity is evaluated by in silico studies for all compounds synthesized.

Mancozeb is a fungicide of the dithiocarbamate functional group, and it is widely used in agriculture to control various fungal diseases. Thus, studies detailing its toxicological characteristics are necessary, as the population may be exposed through the consumption of food or water contaminated with mancozeb. The aim of this study was to evaluate the cytotoxic, genotoxic, and mutagenic potentials of this dithiocarbamate using the Allium cepa L. test system as well as its cytotoxicity in erythrocytes of female rats (Rattus norvegicus). The meristematic roots of A. cepa bulbs were exposed to various concentrations of mancozeb (62.5, 125, 250, and 500 mg/L) for 24, 48, and 72 h to determine cytotoxicity by evaluating the mitotic index (MI), chromosomal aberrations (CA), and nuclear anomalies (NA) for genotoxicity analysis and micronuclei (MN) for mutagenicity analysis. Distilled water and copper sulfate (0.0006 mg/L) were used as the negative control (NC) and positive control (PC), respectively. The MI and the sum of CA and NA of all the mancozeb concentrations showed a significant difference (p ≤ 0.05) in relation to the NC, indicating possible cytotoxicity and genotoxicity induced by mancozeb. Additionally, MN significantly increased with mancozeb concentration from 250 mg/L to 500 mg/L in 24 h when compared to NC. In another study model, mancozeb showed to be cytolytic at concentrations starting from 125 mg/L. Therefore, these results indicate that mancozeb causes cytogenetic alterations and mutagenicity at lower concentrations than those used in agriculture, which emphasizes the need for more care when managing this fungicide.

Ramelteon (RMLT) is a melatonin receptor agonist that it has antioxidative and anti-inflammatory effects associated with DNA damage through different mechanisms of action. In this regard, we investigated the potential usefulness of RMLT as a protective agent against methotrexate (MTX)-induced DNA damage. Four groups were constituted from 32 Wistar albino rats: Negative control, RMLT, MTX, and MTX + RMLT. Twenty mg/kg MTX (i.p., single dose) and RMLT 10 mg/kg (oral, 7 days) was administered. Comet assay was used and the parameter %TailDNA was used to detect DNA damage. %TailDNA was 4.90 ± 0.19 in the control group, 7.85 ± 0.33 in the MTX group, 5.49 ± 0.24 in the RMLT group, and 5.86 ± 0.23 in the MTX + RMLT group. While there was a significant increase in DNA damage in the MTX-treated group compared to the control group, there was a significant reduction in DNA damage in the MTX + RMLT group, compared to the MTX group (p < 0.001). In conclusion, it was observed that combined treatment with RMLT significantly reduced MTX-induced DNA damage.
Investigate the possible protective effect of RMLT against DNA damage caused by MTX using the comet method.The DNA damage of RMLT treated group was significantly reduced compared to group and MTX group. (p < 0.001).Combined treatment with MTX significantly reduces MTX-induced DNA damage.

Introduction Guided tissue regeneration (GTR) is integral to periodontal therapy, facilitating the repair of osseous defects. Due to the widespread use of bovine pericardium (BP) in GTR, a thorough investigation into its genotoxicity is essential for patient safety and treatment efficacy. This study aimed to evaluate the genotoxic effects of local BP in GTR for periodontal osseous defects. Materials and methods The Bacterial Reverse Mutation Assay (Ames test) was used to assess the genotoxic potential of local BP. An exogenous metabolic activation system was employed to evaluate the direct effects of the material on bacterial cells. Results The study investigated the mutagenic effects of local BP across multiple strains of Salmonella typhimurium, utilizing concentrations ranging from 0.3125 mg/plate to 5 mg/plate. While some variability was observed in revertant counts, the generally low SDs suggest a consistent response to the test substance. The maximum revertant count for each strain did not significantly exceed the mean values, indicating the absence of notable outliers or exceptionally high revertant counts at any specific concentration. Based on the data and toxicity assessment criteria, there is insufficient evidence to suggest that the experimental material induces genotoxic effects in the tested bacterial strains under the provided experimental conditions. Conclusion This study assessed the mutagenic potential of local BP membranes used in GTR with the Ames test. Results showed no evidence of mutagenicity, as revertant counts did not exceed twice the negative control in all bacterial strains with exogenous metabolic activation. This suggests that bovine pericardium membranes are safe for medical use under the test conditions. The study highlights the biocompatibility and non-mutagenic nature of BP membranes in GTR for periodontal therapy.

BACKGROUND: Discussion of the benefits of moderate alcohol consumption is ongoing. Broadly, research focusing on ethanol consumption tends to report no benefits. However, studies that distinguish between different types of alcoholic beverages, particularly beers, often reveal positive effects. The present study evaluated the genotoxic and mutagenic effects of moderate chronic consumption of India Pale Ale (IPA) craft beer. Sixty-four adult male Swiss mice were used and divided into control and treatment groups receiving water, IPA beer with 55.23 g of ethanol per liter of beer, aqueous solution with 55.23 g of ethanol per liter, and hop infusion ad libitum for 30 days. After this period, the animals were genetically evaluated with a comet assay. For the ex vivo comet assay, blood was collected and exposed to hydrogen peroxide (H2O2). For the in vivo assay, the alkylating agent cyclophosphamide (CP) was administered to the groups after blood collection and sacrificed after 24 h. Brain, liver, and heart tissues were analyzed. Bone marrow was collected and submitted to the micronucleus test.
RESULTS: The groups treated with IPA beer, ethanol, and hops did not show genotoxic and mutagenic action in the blood, brain, heart, or liver. The antigenotoxic action of IPA beer and hops was observed in both in vivo and ex vivo models, showing a similar reduction in DNA damage caused by CP. There was no significant difference between the groups with regard to the formation of micronuclei by CP.
CONCLUSIONS: Moderate chronic consumption of IPA beer and hops infusion showed antigenotoxic effects in mice but no antimutagenic action. © 2024 Society of Chemical Industry.

Introduction Collagen plays a vital role in maintaining the structural integrity of dentin, and its modification with bioactive compounds can enhance its mechanical properties and bonding capabilities. Aim This study aimed to evaluate the genotoxic effects of grape seed extract (GSE) and marine collagen peptide (MCP) on dental pulp-derived primary cells. Methodology Human dental pulp stem cells were isolated, cultivated, and then treated with GSE and marine collagen peptides. DNA fragmentation was assessed using DAPI (4\',6-diamidino-2-phenylindole) staining. Statistical analysis was performed using SPSS version 20 (IBM Corp., Armonk, NY, USA). Results The results showed that GSE exhibited a minimum level of cell death compared to marine collagen peptides. The viable cell count increased steadily over three days in all groups, with the control group showing the highest number of viable cells. The differences in viable cell count among the groups were statistically significant. Conclusion This study suggests that GSE and marine collagen peptides are highly biocompatible with dental pulp cells and could be considered for further clinical studies.

UNASSIGNED: The Mediterranean thistle Atractylis gummifera L. (Asteraceae; AG) has diterpenoid glucosides; atractyloside and carboxyatractyloside that interact with mitochondrial protein adenine nucleotide translocator (ANT) and resulted in ATP inhibition. Despite its well-known toxicity, acute poisonings still occur with this plant. Although most symptoms are attributed to ANT and diterpenoids interaction, in-depth investigation of the effects of AG extract on various cellular processes has not been performed.
UNASSIGNED: We tested in vitro induction of mitochondrial permeability transition pore (MPTP) opening in bovine liver mitochondria and evaluated its cytotoxicity and genotoxicity using Allium cepa test. Cell division, mitotic index (MI) and total chromosomal and mitotic aberrations (TAs), that all seem potentially affected by ATP shortage, were studied in root cells of Allium cepa exposed to Atractylis gummifera extract.
UNASSIGNED: With the two different doses of two purified AG fractions, stronger induction of MPTP was observed compared to the induction with the standard pure atracyloside. Aqueous AG extract exerted inhibition root growth in A. cepa at 6 different doses. The TAs was increased in a dose-dependent manner too, while mitotic index was decreased at the same doses. Evaluation of mitotic phases revealed mitodepressive effect of AG on A. cepa roots.
UNASSIGNED: this work highlights cellular and mitochondrial adverse effects of Atractylis gummifera extracts. A purified fraction that likely corresponds to ATR derivatives induces MPTP opening leading to swelling of mitochondria and its dysfunction. Allium cepa test provides the evidence for A. gummifera genotoxicity and cytotoxicity.

Chemotherapy has already proven widely effective in treating cancer. Chemotherapeutic agents usually include DNA damaging agents and non-DNA damaging agents. Assessing genotoxic effect is significant during chemotherapy drug development, since the ability to attack DNA is the major concern for DNA damaging agents which relates to the therapeutic effect, meanwhile genotoxicity should also be evaluated for chemotherapy agents\' safety especially for non-DNA damaging agents. However, currently applicability of in vitro genotoxicity assays is hampered by the fact that genotoxicity results have comparatively high false positive rates. γ-H2AX has been shown to be a bifunctional biomarker reflecting both DNA damage response and repair. Previously, we developed an in vitro genotoxicity assay based on γ-H2AX quantification using mass spectrometry. Here, we employed the assay to quantitatively assess the genotoxic effects of 34 classic chemotherapy agents in HepG2 cells. Results demonstrated that the evaluation of cellular γ-H2AX could be an effective approach to screen and distinguish types of action of different classes of chemotherapy agents. In addition, two crucial indexes of DNA repair kinetic curve, i.e., k (speed of γ-H2AX descending) and t50 (time required for γ-H2AX to drop to half of the maximum value) estimated by our developed online tools were employed to further evaluate nine representative chemotherapy agents, which showed a close association with therapeutic index or carcinogenic level. The present study demonstrated that mass spectrometric quantification of γ-H2AX may be an appropriate tool to preliminarily evaluate genotoxic effects of chemotherapy agents.

New mixtures of pesticides are being placed on the market to increase the spectrum of phytosanitary action. Thus, the eco(geno)toxic effects of the new commercial mixture named Platinum Neo, as well as its constituents the neonicotinoid Thiamethoxam and the pyrethroid Lambda-Cyhalothrin, were investigated using the species Daphnia magna, Raphidocelis subcapitata, Danio rerio, and Allium cepa L. The lowest- and no-observed effect concentration (LOEC and NOEC) were measured in ecotoxicological tests. While Thiamethoxam was ecotoxic at ppm level, Lambda-Cyhalothrin and Platinum Neo formulation were ecotoxic at ppb level. The mitotic index (MI), chromosomal aberrations and micronucleus [MN] frequency were measured as indicators of phytogenotoxicity in A. cepa plants exposed for 12 hours to the different insecticides and their mixture under different dilutions. There were significant alterations in the MI and MN frequency in comparison with the A. cepa negative control group, with Thiamethoxam, Lambda-Cyhalothrin, and Platinum Neo treatments all significantly reducing MI and increasing MN frequency. Thus, MI reduction was found at 13.7 mg L-1 for Thiamethoxam, 0.8 μg L-1 for Lambda-Cyahalothrin, and 2.7:2 μg L-1 for Platinum Neo, while MN induction was not observed at 14 mg L-1 for Thiamethoxam, 0.8 μg L-1 for Lambda-Cyahalothrin, and 1.4:1 μg L-1 for Platinum Neo. The insecticide eco(geno)toxicity hierarchy was Platinun Neo > Lambda-Cyhalothrin > Thiamethoxam, and the organism sensitivity hierarchy was daphnids > fish > algae >A. cepa. Eco(geno)toxicity studies of new pesticide mixtures can be useful for management, risk assessment, and avoiding impacts of these products on living beings.

Psychotria carthagenensis is a shrubby plant, often consumed by traditional populations in religious rituals. Previous studies have shown that this plant\'s infusion can inhibit the activity of Acetylcholinesterase (AChE) in rats. Despite the therapeutic potential, there is a lack of research regarding its possible toxicological and genotoxic effects. Hence, this study aimed to analyze the chemical profile of the ethanol extract from P. carthagenensis leaves by LC-DAD-MS and assess its possible toxicity and genotoxicity in zebrafish (Danio rerio). Adult zebrafish (N = 9/group) were exposed at different concentrations and the LC50 was calculated. Frequencies of micronucleus (MN) and nuclear abnormalities (NA) were estimated for genotoxic effects, and degree of tissue changes (DTC) was used to assess the liver and gill histopathology. From the LC-DAD-MS analyses, the identified compounds included N-fructosyl valine, ethyl hexoside, 5-O-E-caffeoylquinic acid, N-feruloylagmatime, roseoside, di-O-deoxyhexoyl-hexosyl quercetin, loiolide, and oleamide. The calculated values of LC50 did not vary significantly during the time of exposure. At the concentrations of 1.25, 2.5, 3.75, 5, 7.5, 10 and 15 mg/L, there was no genotoxicity, and only low to moderate toxicity for the tissues was observed, despite mortality of 100% at doses of 20-100 mg/L of P. carthagenensis ethanolic leaf extract. There were changes in cytoplasm of hepatocytes at 1.25 mg/L, and karyorrhexis, karyolysis and megalocytosis at 10 mg/L. In the gills, the alterations were primary lamellar hyperplasia in all concentrations, and at 10 mg/L, secondary lamellar edema and vascular hyperemia were common. Additionally, the chemical composition of P. carthagenensis was expanded.