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The skin is the largest organ in the body and the only one to come into contact with solar UV radiation (UVR). UVA (320-400 nm) is a significant contributor to UV-related skin damage. The UVA spectrum makes up over 95% of solar-UV energy reaching the earth's surface causing the majority of the visible signs of skin photoaging. Many consumer products also emit UVA, including nail dryers. There have been sporadic reports suggesting that these units may be contributing to skin cancer incidence. This notion was recently bolstered by a finding that nail dryer-irradiated mammalian skin cells develop a mutational signature consistent with UVA exposure. This report was surprising considering the comparatively low level of UVA to which the skin is exposed during nail treatments. In this research, we investigated how UVA-emitting devices caused cytotoxic/genotoxic impact after only low levels of UVA exposure. Our data showed that levels of UVA in the unit are highly variable and location dependent. We confirm previous reports that using prolonged exposure protocols could induce significant levels of DNA damage. It was also determined that UV-induced DNA damage only partially correlated with the level of UVA fluency. On investigation, we found that the unit had a rapid increase in internal temperature when in use. Exposing human cells to these elevated temperatures acted synergistically with UVA to magnify the cytotoxic and genotoxic impact of UV irradiation. [ABSTRACT FROM AUTHOR]

In recent years, nitrosamine impurities in pharmaceuticals have been subject to intense regulatory scrutiny, with nitrosamine drug substance-related impurities (NDSRIs) treated as cohort of concern impurities, regardless of predicted mutagenic potential. Here, we describe a case study of the NDSRI N-nitroso-hydrochlorothiazide (NO-HCTZ), which was positive in the bacterial reverse mutation (Ames) test but is unstable under the test conditions, generating formaldehyde among other products. The mutagenic profile of NO-HCTZ was inconsistent with that expected of a mutagenic nitrosamine, exhibiting mutagenicity in the absence of metabolic activation, and instead aligned well with that of formaldehyde. To assess further, a modified Ames system including glutathione (3.3 mg/plate) to remove formaldehyde was developed. Strains used were S. typhimurium TA98, TA100, TA1535, and TA1537, and E. coli WP2 uvrA/pKM101. In this system, formaldehyde levels were considerably lower, with a concomitant increase in levels of S-(hydroxymethyl)glutathione (the adduct formed between glutathione and formaldehyde). Upon retesting NO-HCTZ in the modified system (1.6–5000 µg/plate), a clear decrease in the mutagenic response was observed in the strains in which NO-HCTZ was mutagenic in the original system (TA98, TA100, and WP2 uvrA/pKM101), indicating that formaldehyde drives the response, not NO-HCTZ. In strain TA1535, an increase in revertant colonies was observed in the modified system, likely due to a thiatriazine degradation product formed from NO-HCTZ under Ames test conditions. Overall, these data support a non-mutagenic designation for NO-HCTZ and demonstrate the value of further investigation when a positive Ames result does not align with the expected profile. [ABSTRACT FROM AUTHOR]

Simple Summary: Nanoparticles (NPs) have received significant consideration because of their special properties and valuable applications in numerous segments. In the current era, the fast growth of NP manufacturing and their plentiful uses puts the environment at additional risks. To explicate the noxious effects of NPs, numerous plant bioassays have been proposed. Since Pisum sativum L. has complex mitotic dynamics, it is a test plant used to assess the genotoxic effects of environmental pollutants. Using the Pisum sativum test system, this work was designed to assess the toxicity potential of CuO NPs by morphological (SG and RL) and genotoxic (CD, MI, CKP, MNF, and CAF) methods. Even though cytogenetic analyses of environmental pollutants in plants have been reported previously, this is the first work of its type to demonstrate the morphological and genotoxic effects of CuO NPs in Pisum sativum. These studies are very essential, since the pea is a vital food grain crop and a tremendous source of ayurvedic medications and manure, as well as its use as a vegetable. The speedy growth of copper oxide nanoparticle (CuO NP) manufacturing due to their wide application in industries has caused concerns due to their increased discharge into the environment from both purposeful and accidental sources. Their presence at an elevated concentration in the environment can cause potential hazards to the plant kingdom, specifically to staple food crops. However, limited research is available to determine the consequences of CuO NPs. The present study aimed to assess the morphological and cytological changes induced by CuO NPs on Pisum sativum L., a key staple food crop. Seeds of Pisum sativum were exposed to various concentrations of CuO NPs (0, 25, 50, 75, 100, and 125 ppm) for 2 h, and their effects on seed germination (SG), radicle length (RL), cell proliferation kinetics (CPK), mitotic index (MI), cell death (CD), micronucleus frequency (MNF), and chromosomal aberration frequency (CAF) were studied. The results indicate a significant reduction in SG, RL, CPK, and MI and a significant dose-dependent increase in CD, MNF, and CAF. CuO NP treatment has led to abnormal meiotic cell division, increased incidence of micronucleus frequency, and chromosomal aberration frequency. Additionally, the CuO NP-treated groups showed an increase in the percentage of aberrant meiotic cells such as laggard (LG), double bridge (DB), stickiness (STC), clumped nuclei (CNi), precocious separation (PS), single bridge (SB), and secondary association (SA). CuO NP treatment led to reductions in SG as follows: 55% at 24 h, 60.10% at 48 h, and 65% at 72 h; reductions in RL as follows: 0.55 ± 0.021 cm at 24 h, 0.67 ± 0.01 cm at 48 h, and 0.99 ± 0.02 cm at 72 h; reductions in CPK as follows: 34.98% at prophase, 7.90% at metaphase, 3.5% at anaphase, and 0.97% at telophase. It also led to a 57.45% increase in CD, a 39.87% reduction in MI, and a 60.77% increase in MNF at a higher concentration of 125 ppm. The findings of this study clearly show that CuO NPs have a genotoxic effect on the food crop plant Pisum sativum. [ABSTRACT FROM AUTHOR]

Hexaconazole (HEX), a widely used triazole fungicide in agriculture, was investigated for its hepatotoxic effects on albino Wistar rats. Compared to the control rats, the treated rats showed a significant increase in absolute and relative liver weight over both 3 months (p < 0.05) and 6 months (p < 0.001). Oxidative biomarkers indicated a notable rise in malondialdehyde (MDA) by 137% (p < 0.001), increased reduced glutathione (GSH) by 32% (p < 0.01), and significant reductions in antioxidant enzymes, including a 63% decrease in catalase (CAT, p < 0.001) and a 15% decrease in superoxide dismutase (SOD, p < 0.01). Glutathione-S-transferase (GST) levels also decreased significantly after 3 and 6 months (p < 0.05). The micronucleus test in liver cells indicated an elevation in the appearance of micronuclei in rats treated with HEX for 6 months (p < 0.01). This study demonstrates, for the first time, that HEX can induce genotoxicity in the liver. [ABSTRACT FROM AUTHOR]

Iron oxide nanoparticles (IONPs) have been extensively explored in biomedicine, bio-sensing, hyperthermia, and drug/gene delivery, attributed to their versatile and tunable properties. However, owing to its numerous applications, the functionalization of IONPs with appropriate materials is in demand. To achieve optimal functionalization of IONPs, polydopamine (PDA) was utilized due to its ability to provide a superior functionalized surface, near-infrared light absorption, and adhesive nature to customize desired functionalized IONPs. This notion of involving PDA led to the successful synthesis of magnetite-PDA nanoparticles, where PDA is surface-coated on magnetite (Fe3O4@PDA). The Fe3O4@PDA nanoparticles were characterized using techniques like TEM, FESEM, PXRD, XPS, VSM, and FTIR, suggesting PDA's successful attachment with magnetite crystal structure retention. Human serum albumin (HSA), the predominant protein in blood plasma, interacts with the delivered nanoparticles. Therefore, we have employed various spectroscopic techniques, along with cytotoxicity, to inspect the effect of Fe3O4@PDA NPs on the stability and structure of HSA. The structural alterations were examined using circular dichroism (CD) and synchronous fluorescence spectroscopy (SFS). It has been observed that there are no structural perturbations in the secondary structure of the HSA protein after interaction with Fe3O4@PDA. Studies using steady-state fluorescence revealed that the inherent fluorescence intensities of HSA were suppressed after interaction with Fe3O4@PDA. In addition, temperature-dependent fluorescence measurements suggested that the type of quenching consists of both static and dynamic quenching simultaneously. A cytotoxicity study in Drosophila melanogaster larvae revealed no cytotoxic effects but did show a minor genotoxic effect only at higher concentrations. [ABSTRACT FROM AUTHOR]

Background: Carbamazepine is one of the most widely used antiepileptic drugs. Carbamazepine has been shown to be toxic to cells. Cilostazol, an antiplatelet agent, has known antioxidant, antiproliferative, anti-inflammatory, and anti-tumor effects. Objective: This study aimed to explore whether carbamazepine and cilostazol exert genotoxic and/or cytotoxic effects in human cultured blood lymphocytes and the impact of combining both drugs on such effects. Methods: Genotoxicity was examined using sister chromatid exchange (SCE) assay, while cytotoxicity was evaluated by cell kinetic assays (mitotic and proliferative indices). Results: Study findings have revealed that carbamazepine markedly increased SCEs (p0.05). Carbamazepine increased the cell proliferative index (p

Nitrosamine impurities identified in several pharmaceuticals during recent times has raised concerns leading to product recalls worldwide and necessitating sensitive liquid and gas chromatographic methods for trace level detection of nitrosamine impurities. This study developed and validated a ultra-fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) method for the quantification of NDMA in Levosulpuride drug substance and tablet formulation. Current method utilizes a triple quadrupole analyzer, atmospheric pressure chemical ionization (APCI) ionization source and multiple reaction monitoring (MRM) scan mode for the analysis. Chromatographic separation was achieved on a Gemini NX-C18 column (150 × 4.6 mm, 3 µm) maintained at 40 °C. The mobile phase consisted of a binary gradient of solvent A (0.1 % formic acid in water) and solvent B (methanol), with a total run time of 18 minutes. Current method achieved excellent linearity, recovery, precision, and sensitivity. Greenness of the developed method was evaluated using the GAPI, AGREE, and AES metrics. Current method is sensitive and selective for NDMA in levosulpuride drug substance and tablet formulations and can be employed for routine quality control analysis in pharmaceutical industry.

Many medicinal plant extracts have been proven to have significant health benefits. In contrast, research has shown that some medicinal plant extracts can be toxic, genotoxic, mutagenic, or carcinogenic. Therefore, evaluation of the genotoxicity effects of plant extracts that are used as traditional medicine is essential to ensure they are safe for use and in the search for new medication. This review summarizes 52 published studies on the genotoxicity of 28 plant extracts used in traditional medicine. A brief overview of the selected plant extracts, including, for example, their medicinal uses, pharmacological effects, and primary identified compounds, as well as plant parts used, the extraction method, genotoxic assay, and phytochemicals responsible for genotoxicity effect were provided. The genotoxicity effect of selected plant extracts in most of the reviewed articles was based on the experimental conditions. Among different reviewed studies, A total of 6 plant extracts showed no genotoxic effect, other 14 plant extracts showed either genotoxic or mutagenic effect and 14 plant extracts showed anti-genotoxic effect against different genotoxic induced agents. In addition, 4 plant extracts showed both genotoxic and non-genotoxic effects and 6 plant extracts showed both genotoxic and antigenotoxic effects. While some suggestions on the responsible compounds of the genotoxicity effects were proposed, the proposed responsible phytochemicals were not individually tested for the genotoxicity potential to confirm the findings. In addition, the mechanisms by which most plant extracts exert their genotoxicity effect remain unidentified. Therefore, more research on the genotoxicity of medicinal plant extracts and their genotoxicity mechanisms is required.

N-nitrosamines (NSAs) and Nitrosamine Drug Substance Related Impurities (NDSRIs) are class of compounds that contains the nitroso functional group. These compounds are carcinogens and mutagens for both humans and animals. As a result, all global regulatory agenesis are requiring risk assessments of NSAs in each pharmaceutical product. The present research aims to provide a single pre-packaged mass spectrometry method parameter set, which includes Ultra performance liquid chromatography and a triple quadrupole mass spectrometer (UPLC-MS-MS) configuration technique for qualifying and quantifying NNHCT in HCT. The analysis was performed on a YMC ODS-A liquid chromatography column with an oven temperature of 35 °C. In this method, mobile phase was prepared by mixing 10 mM ammonium formate buffer and acetonitrile was mixed in the ratio of 60:40 (v/v) with an isocratic program and a flow rate of 0.8 mL/min. The mass detector was used along with electrospray ionization (ESI) Negative mode with multiple reaction monitoring (MRM). The method has been validated in accordance with the current regulatory guidelines and shown the ability to detect NNHCT with a LOQ of 0.01 ppm and LOD of 0.005 ppm.

Cancer is a disease resulting from the disruption of cell cycle regulation, leading to the abnormal and unchecked proliferation of cells. Medicinal plants are rich in various bioactive phytochemicals or nutritional compounds. The aim is to determine the cytotoxic and genotoxic effects of ethanolic extracts of Macaranga peltata leaves on human oral cancer cell lines. The study setting was centre for Research on Molecular and Applied Sciences, Azeezia College of Dental Sciences and Research. The study design is a Comparative In Vitro study. Shade dried leaves of Macaranga peltata were subjected to Soxhlet extraction, and ethanolic extract was prepared. In vitro cytotoxic effects on human oral cancer cell lines were evaluated by (3-(4,5-dimethyl thiazole-2yl)-2,5–diphenyl tetrazolium bromide) MTT assay, and genotoxic effect was evaluated by comet assay. Untreated cell lines were used as control, and 5-fluorouracil was used as positive control. All experiments were performed in triplicates, and results were represented as Mean+/- SE. One-way ANOVA and Dunnet test were performed to analyze data. ***P < 0.001 compared with the control group. The ethanolic extract of Macaranga peltata exhibited cytotoxicity against oral cancer cells (LC50: 40.193089 μg/ml). There was a concentration-dependent increase in cell death, and at 100 μg/ml, the extract was most effective, causing 50% inhibition of viability. The comet assay showed significant genotoxic effects compared with 5-fluorouracil and untreated oral cancer cell lines. The ethanolic extract of Macaranga peltata leaves was subjected to MTT assay and comet using KB cell lines. The study concludes that the extract gave promising result for the anticancer activity on the KB cell lines producing cytotoxicity and genotoxicity.

The contamination of seafood by heavy metals is a rising health issue in the context of pollution caused by increasing industrialization and urbanization. Crustaceans are particularly susceptible to heavy metal pollution in aquatic ecosystems due to their benthic and sedimentary lifestyle. Here we review crustaceans contamination by heavy metals with a focus on metal sources and dynamics, interaction of metals with other pollutants, metal analysis, bioconcentration and bioaccumulation, toxicity, and strategies to control metals. We observed that crustaceans tend to accumulate more heavy metals than other aquatic animals. Consequently, in certain regions of the world, consuming crustaceans as food may potentially threaten human health. The bioavailability, transport, and interaction of heavy metals with other pollutants depend on various factors, potentially leading to differential toxicity. Heavy metals induce multiple toxic effects on crustaceans, including metabolic dysfunction, genotoxic effects, respiratory impairments, DNA damage, sperm mobility, and quantity, and these poisonous effects will intensify with prolonged exposure time and increasing concentration. The concentration of heavy metals in crustacean samples is usually determined by inductively coupled plasma optical emission spectrometry and mass spectrometry. Approaches to reducing this potential threat include proper industrial wastewater treatment and using low-cost adsorbent materials in aquaculture. [ABSTRACT FROM AUTHOR]

Cancer is a disease resulting from the disruption of cell cycle regulation, leading to the abnormal and unchecked proliferation of cells. Medicinal plants are rich in various bioactive phytochemicals or nutritional compounds. The aim is to determine the cytotoxic and genotoxic effects of ethanolic extracts of Macaranga peltata leaves on human oral cancer cell lines. The study setting was centre for Research on Molecular and Applied Sciences, Azeezia College of Dental Sciences and Research. The study design is a Comparative In Vitro study. Shade dried leaves of Macaranga peltata were subjected to Soxhlet extraction, and ethanolic extract was prepared. In vitro cytotoxic effects on human oral cancer cell lines were evaluated by (3-(4,5-dimethyl thiazole-2yl)-2,5-diphenyl tetrazolium bromide) MTT assay, and genotoxic effect was evaluated by comet assay. Untreated cell lines were used as control, and 5-fluorouracil was used as positive control. All experiments were performed in triplicates, and results were represented as Mean+/- SE. One-way ANOVA and Dunnet test were performed to analyze data. P < 0.001 compared with the control group. The ethanolic extract of Macaranga peltata exhibited cytotoxicity against oral cancer cells (LC50: 40.193089 µg/ml). There was a concentration-dependent increase in cell death, and at 100 µg/ml, the extract was most effective, causing 50% inhibition of viability. The comet assay showed significant genotoxic effects compared with 5-fluorouracil and untreated oral cancer cell lines. The ethanolic extract of Macaranga peltata leaves was subjected to MTT assay and comet using KB cell lines. The study concludes that the extract gave promising result for the anticancer activity on the KB cell lines producing cytotoxicity and genotoxicity. [ABSTRACT FROM AUTHOR]

Drug impurity profile studies have changed significantly during the past ten years, as demonstrated by pharmacopeia and regulatory standards. This review article aims to give viewers a thorough understanding of the numerous facts of impurity profiling in relation to regulatory criteria. Comprehensive information on residual solvents, water impurities, elemental impurities, carcinogenicity and an overview of the most critical components of genotoxic contaminants. To ensure the drug products fulfill the minimal acceptable quality standards and a number of pharmacopoeias have created monographs. ICH, EMEA, USFDA and European Pharmacopeia recommendations are just a few of the regulatory bodies that offer rules to reduce the amount of contaminants in medications. In order to prevent impurities, industry, research and development sectors widely employ different spectrum analyses including HPLC, LC/MS and GC/MS. It involves the recall of medications because of these contaminants. The significance of understanding genotoxic impurities as a crucial element of the impurity profile in medications is emphasized in this abstract. [ABSTRACT FROM AUTHOR]

The speedy growth of copper oxide nanoparticle (CuO NP) manufacturing due to their wide application in industries has caused concerns due to their increased discharge into the environment from both purposeful and accidental sources. Their presence at an elevated concentration in the environment can cause potential hazards to the plant kingdom, specifically to staple food crops. However, limited research is available to determine the consequences of CuO NPs. The present study aimed to assess the morphological and cytological changes induced by CuO NPs on Pisum sativum L., a key staple food crop. Seeds of Pisum sativum were exposed to various concentrations of CuO NPs (0, 25, 50, 75, 100, and 125 ppm) for 2 h, and their effects on seed germination (SG), radicle length (RL), cell proliferation kinetics (CPK), mitotic index (MI), cell death (CD), micronucleus frequency (MNF), and chromosomal aberration frequency (CAF) were studied. The results indicate a significant reduction in SG, RL, CPK, and MI and a significant dose-dependent increase in CD, MNF, and CAF. CuO NP treatment has led to abnormal meiotic cell division, increased incidence of micronucleus frequency, and chromosomal aberration frequency. Additionally, the CuO NP-treated groups showed an increase in the percentage of aberrant meiotic cells such as laggard (LG), double bridge (DB), stickiness (STC), clumped nuclei (CNi), precocious separation (PS), single bridge (SB), and secondary association (SA). CuO NP treatment led to reductions in SG as follows: 55% at 24 h, 60.10% at 48 h, and 65% at 72 h; reductions in RL as follows: 0.55 ± 0.021 cm at 24 h, 0.67 ± 0.01 cm at 48 h, and 0.99 ± 0.02 cm at 72 h; reductions in CPK as follows: 34.98% at prophase, 7.90% at metaphase, 3.5% at anaphase, and 0.97% at telophase. It also led to a 57.45% increase in CD, a 39.87% reduction in MI, and a 60.77% increase in MNF at a higher concentration of 125 ppm. The findings of this study clearly show that CuO NPs have a genotoxic effect on the food crop plant Pisum sativum.

Açaí (Euterpe oleracea MART.) has been the target of several studies due to its strong antioxidant potential and possible cytoprotective effect, thus providing health benefits to the population. Fluconazole is a widely known and used drug in the treatment of fungal diseases. However, the literature shows that this drug can show cytotoxic effects, as well as cause DNA damage. In this regard, the present study aims to assess the putative cytoprotective effect of clarified açaí (CA) pulp extract on VERO cells exposed to fluconazole. It was observed in the MTT assay that CA was able to increase the viability of cells exposed to the antifungal agent in three different times of exposure (24, 48 and 72 h). Similarly, the results of the comet assay demonstrated that CA was able to decrease the genotoxic effects of fluconazole significantly. Thus, we conclude that, under the assessed conditions, CA shows cytoprotective effects against the damage caused by fluconazole. [ABSTRACT FROM AUTHOR]

Heavy metals and their genotoxic effects in captive Indian Peafowl (Pavo cristatus) residing in various regions of Punjab, Pakistan, specifically, Wildlife Park Bahawalpur (WPB), Jallo Wildlife Park Lahore (JWPL), and Wildlife Park Murree (WPM) were evaluated in blood, feathers, eggshell and egg content samples. The Single-cell gel electrophoresis (Comet) assay was performed to evaluate DNA damage. The results showed that the concentration of Cr was significantly high (P

Heavy metals and their genotoxic effects in captive Indian Peafowl (Pavo cristatus) residing in various regions of Punjab, Pakistan, specifically, Wildlife Park Bahawalpur (WPB), Jallo Wildlife Park Lahore (JWPL), and Wildlife Park Murree (WPM) were evaluated in blood, feathers, eggshell and egg content samples. The Single-cell gel electrophoresis (Comet) assay was performed to evaluate DNA damage. The results showed that the concentration of Cr was significantly high (P < 0.05) in Blood (3.79 µg/g), Feather (4.87 µg/g), Egg shell (51.02 µg/g) and Egg Content (13.59 µg/g) samples of Jallo Wildlife Park Lahore followed by Pb, Mn, Ni and Co. The highest (P < 0.05) metal accumulation was found in eggshell samples due to its porous structure as compared to other samples. Likewise region-wise analysis showed that Jallo Wildlife Park Lahore appeared to be more polluted than WPB and WPM. Indian Peafowl kept at WPM and JWPL exhibited higher levels of genotoxicity compared to the birds kept at WPB. This disparity can be attributed to the increased exposure to pollution and heightened stress experienced by the peafowl in the former two locations. This study concluded that among all the three study sites of Punjab, the WPB is most suitable for housing captive animals and birds. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the toxic effects of most commonly used plasticizer Di-(2-ethylhexyl) phthalate (DEHP) in the peripheral blood and liver of adult female mice, and protective effect of a commonly used spice (Allium sativum) against DEHP induced pathology. Animals were treated with aqueous garlic extract, DEHP, and DEHP+Garlic extract (aqueous) at dosage of 500 mg/kg body weight each (intra-gastric treatment) (n=10) for 28 days. DEHP treatment resulted in a significant decline in mean body weight while a significant increase in the mean liver weight was noticed as compared to the control group. Results indicated various liver histopathologies in DEHP exposed animals including sinusoid dilation, deshaped hepatic parenchyma cells with nuclear anomalies, and increased number of inflammatory cells. A significant increase in average cross-sectional area (ACSA) of the central vein and number of mononucleated, binucleated, and oval cells was noticed in the DEHP group as compared to the garlic group. A significant increase in cellular diameter of hepatocytes in DEHP and DEHP+Garlic group was also observed. Aqueous garlic extract treatment significantly ameliorated the DEHP-induced histopathological and micrometric alterations in the DEHP+Garlic group. Serum ALT, AST, and ALP levels were significantly decreased in the DEHP+Garlic group as compared to the DEHP group. DEHP treatment caused different nuclear anomalies in the white blood cells of female mice, however, no significant signs of recovery were observed by the aqueous garlic extract treatment. The results showed that DEHP is highly toxic to the female mice's liver, and garlic extract could potentially protect and rescue DEHP-induced liver damage in the female mice. [ABSTRACT FROM AUTHOR]

Genotoxic impurities interact with DNA and may subsequently induce mutations. Olmesartan, is a medication used to treat high heart failure, blood pressure, and diabetic kidney disease. Sodium azide has been used in the process and it is responsible for genotoxic impurities. The limit of genotoxic impurities are very stringent. The aim of this study is to determination of the four-process related genotoxic impurities in olmesartan medoxomil tablet by HPLC. The target was to develop a simple HPLC method instead of highphenated instrument. A gradient program was used to separate four genotoxic impurities. C18 Kromasil (250mm x 4.6 mm) 5 µm column was used. Additionally, a ghostbusting column having dimensions of 50mm x 4.6 mm was deployed. Orthophosphoric acid, in the mobile phase A, was 0.1%. Methanol and acetonitrile were combined in the mobile phase B at a volume ratio of 75:925. There was a 1.0 mL/min flow. A 210nm wavelength was used for analyte detection. Azido methyl impurity, Trityl azide, KL-2 azide, and KL-2 diazide were all found specific and retention times are 11.19, 37.41, 49.16, and 54.19 respectively. Ranges of 0.1741 to 1.1607 ppm, 0.1729 to 1.1525 ppm, 0.1745 to 1.1630 ppm, and 0.1696 to 1.1305 ppm, respectively. The coefficient of determination r was likewise found to be higher than 0.99. The RP-HPLC process is straightforward, reliable, precise, and selective. The ICH criteria were followed in the complete validation of the HPLC method and the validation results show that the method is suitable for usage as intended. [ABSTRACT FROM AUTHOR]

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Objective: The present study aims to evaluate the number of micronuclei (MN) in potentially malignant disorders (PMDs) and oral cancer and correlates them with the control group. Materials and Methods: Subjects included in the study were equally divided into four groups. Exfoliated cells were then obtained from the buccal mucosa using cytological brush. Smears were stained using rapid Pap stain. The smears were observed using a light microscope, and MN was counted out of 10 high-power fields and scored according to PE Tolbert (1992) criteria. Results: The mean MN count was found to be 0.23, 2.10, 3.03, and 3.57 in groups I, II, III, and IV, respectively. The overall intergroup comparison between the four groups was found to be statistically significant with a P value less than 0.05. Conclusion: This study gives a fair assessment that MN assay in exfoliated cells of oral epithelium can be a conducive biomarker while screening for PMDs of the oral cavity in doubtful lesions that are primarily misdiagnosed clinically.

A highly sensitive analytical method has been developed for trace level quantification of formaldehyde in active pharmaceutical ingredient. Formaldehyde is a highly toxic impurity. Determination of formaldehyde by using UV-visible spectroscopy is difficult due to interference of unreacted derivatizing agent; hence, either HPLC-UV or GC-MS are used for the quantification. However, we have developed an indirect method for the quantification of formaldehyde. In this method, in the first step, formaldehyde reacted with excess of 2,4-dinitrophenyl hydrazine (2,4-DNPH). In the second step, the quantification of unreacted 2,4-DNPH was done by detecting its derivative with its scavenger—cinnamaldehyde on a UV-visible spectrophotometer. The developed method is rapid, simple, sensitive and accurate for the quantification of formaldehyde. Linearity of the method was observed in the range of 0.5–3 μg/mL with determination coefficients (r2) > 0.999. The limit of detection and limit of quantification are 0.25 and 0.5 μg/mL, respectively. [ABSTRACT FROM AUTHOR]

IntroductionDNA damage repair (DDR) is an essential process for living organisms and contributes to genome maintenance and evolution. DDR involves different pathways including Homologous recombination (HR), Nucleotide Excision Repair (NER) and Base excision repair (BER) for example. The activity of each pathway is revealed with particular drug inducing lesions, but the repair of most DNA lesions depends on concomitant or subsequent action of the multiple pathways.MethodsIn the present study, we used two genotoxic antibiotics, mitomycin C (MMC) and Bleomycin (BLM), to decipher the interplays between these different pathways in E. coli. We combined genomic methods (TIS and Hi-SC2) and imaging assays with genetic dissections.ResultsWe demonstrate that only a small set of DDR proteins are common to the repair of the lesions induced by these two drugs. Among them, RecN, an SMC-like protein, plays an important role by controlling sister chromatids dynamics and genome morphology at different steps of the repair processes. We further demonstrate that RecN influence on sister chromatids dynamics is not equivalent during the processing of the lesions induced by the two drugs. We observed that RecN activity and stability requires a pre-processing of the MMC-induced lesions by the NER but not for BLM-induced lesions.DiscussionThose results show that RecN plays a major role in rescuing toxic intermediates generated by the BER pathway in addition to its well-known importance to the repair of double strand breaks by HR.

Herbicides are commonly used to control weed. However, some plants are resistant to such products. To identify less harmful herbicides, it is crucial to search for different mechanisms of action. Thymol is an easily acquired allelopathic compound, capable of producing its respective semisynthetic derivative, thymoxyacetic acid. The aim of this study was to determine the effects of thymol and thymoxyacetic acid molecules as bioherbicides in greenhouse at the concentration of 3 mmol L−1 in pre- and postemergence applications in five species: Amaranthus viridis L., Cucumis sativus L., Lactuca sativa L., Eleusine indica L., and Sorghum bicolor L. The initial seedling development and DNA changes were analyzed. These molecules were contrasting with the solvent, in the negative control, and with the glyphosate, in the positive control, promoting phytogenotoxic activities. The toxic effect of thymoxyacetic acid was more effective in preemergence and thymol's in postemergence. We also observed a reduction in the germination speed index and root growth with a negative correlation to the increase in potassium leaching. Damage to the root and shoot of the seedlings was verified at the DNA level, and the phytotoxicity of the plants treated with the herbicide glyphosate was similar to the plants treated with the natural molecules tested. The bioherbicidal effect of thymol and thymoxyacetic acid exacerbates the reduction of the environmental impact caused by the disordered and increased use of residual pesticides. [ABSTRACT FROM AUTHOR]

Trimethylamine (TMA) is produced by the intestinal microbiota as a by-product of metabolism of dietary precursors. TMA has been implicated in various chronic health conditions. However, the effect of TMA in the colon and the underlying mechanism was not clear. In this study, TMA exhibited toxic effects in vitro as well as in vivo. TMA-induced oxidative stress causes DNA damage, and compromised cell membrane integrity leading to the release of LDH outside the cells which ultimately leads to cell death. Besides, TMA also exhibited pronounced increase in cell cycle arrest at G2/M phase in both HCT116 and HT29 cell lines. TMA was found to be genotoxic and cytotoxic as the TMA concentration increased from 0.15 mM. A decreased ATP intracellular content was observed after 24 h, 48 h, and 72 h treatment in a time and dose-dependent manner. For in vivo research, TMA (100 mM, i.p. and intra-rectal) once a week for 12 weeks caused significant changes in cellular morphology of colon and rectum epithelium as assessed by H & E staining. TMA also significantly increased the infiltration of inflammatory cells in the colon and rectal epithelium indicating the severity of inflammation. In addition, TMA caused extensive mucosal damage and distortion in the epithelium, decrease in length of small intestine compared to control mice. In conclusion, these results highlight the detrimental effects of TMA in the colon and rectal epithelium. [ABSTRACT FROM AUTHOR]

Nanomaterial, especially zinc oxide nanoparticles, has entered the manufacture of many materials used in daily lives. The current study aimed to assess the impact of three concentrations of hibiscus rosa zinc oxide nanoparticles (HrZnONPs) and hibiscus rosa extract (Hre) on the liver tissue and DNA fragmentation of liver cells. A total of 35 adult male Wistar rats were grouped as follows: The first group which was the control (n=7) did not receive any treatment. The remaining 28 animals were randomly assigned to four groups. Group 1 (n=7) were subcutaneously injected with 100mg\kg BW of Hibiscus rosa extract for 60 days; the rats in group 2 were subcutaneouslyinjected with 25 mg\kg BW of HrZnONPs for 60 days; rats in group 3 were subcutaneouslyinjected with 75mg\kg BW of HrZnONPs for 60 days; rats in group 4 were subcutaneously injected with 100mg\kg BW of HrZnONPs for 60 days. The liver biomarkers, aspartate aminotransferase (AST), alkaline phosphatase (ALP), and alanine aminotransferase (ALT) have been assessed in serum at zero time, after one month, and after two months of the experiment. At the end of the experiment, all animals were euthanized, the liver was dissected, the specimen underwent a pathohistological investigation, and the percentage of DNA fragmentation was evaluated. The results pointed out that the rats which were treated with HrZnONPs at concentrations of 75 and 100 mg\kg B.W. demonstrated a salient elevation in serum AST, ALT, or ALP activity, a modulation in hepatic tissue architecture, and an elevated percentage of high DNA damage, as compared to those treated with HrZnONPs at a concentration of 25 mg\kg B.W. On the other hand, the recorded data indicated that the administration of Hre has some ameliorative effects on AST, ALP, and ALT levels, histological cross-section, and the value of comet assay for liver cells due to the role of Hre antioxidant. In conclusion, the results of the current study demonstrated that high doses of HrZnONPs had exerted more adverse effects, compared to low doses. Moreover, the findings confirmed the ameliorative impact of Hre on liver biomarkers, a histological cross-section of the liver, and DNA damage.

• The synthesis of new DHPMs utilizing bis-dialdehydes containing active methylene groups has not been documented previously. • The synthesized compounds underwent theoretical in silico ADME prediction analysis using the online tool swiss ADME to evaluate their drug likeness properties. • The MTT (3-(4,5-dimethylthiazol-2-yl)−2,5-diphenyltetrazolium bromide) solution at a concentration of 5 mg/mL was employed to assess the in vitro cytotoxicities of the DHPMs on the A549 cancer cell line. • Cytotoxicity study serves as a crucial springboard, not just for identifying lead candidates, but for meticulously sculpting them into efficacious therapeutic agents. The presented analysis highlights the intriguing cytotoxic potentials of these newly synthesized DHPMs, yet it unveils avenues for further exploration. • The present research focused on the release profiles of DHPM derivatives, which are often used to deliver medication within the body. Ultimately, this paves the way for developing highly effective drug delivery systems with superior clinical performance and improved patient outcomes. • The synthesized dihydropyrimidinones have demonstrated potential as lead compounds for the development of novel antimicrobial agents. • Molecular docking studies were conducted to assess the binding affinity of the compounds with the receptor or protein target, employing a molecular docking tool. • To evaluate the potential for genetic damage (genotoxicity) in the bacterium enterococcus faecalis, DHPMs were tested at concentrations corresponding to 50 % inhibition of bacterial growth (IC50 values). Dihydropyrimidin-2(1H)-ones (DHPMs) are attracting growing interest in synthetic and medical organic chemistry due to their biological and therapeutic potential. In this study, we synthesized DHPM derivatives via the Biginelli reaction from bisdialdehyde to identify lead compounds. Using SWISSADME analysis, we assessed druglikeness features of the DHPM derivatives. Antimicrobial properties, including antibacterial and antifungal activities, were evaluated, and promising compounds were tested for their ability to inhibit A549 lung cancer cell growth. Thin-layer chromatography confirmed product formation, while spectroscopic methods characterized the structures. Lipophilicity values indicated strong oral absorption potential. In vitro drug release and cell viability studies were conducted. DHPMs 7, 8, and B1 exhibited broad-spectrum antimicrobial activity. Molecular docking revealed DHPM 2′s potential in cancer treatment via effective binding with VEGFR-2 kinase. Genotoxic and anticancer activities were assessed, with DHPM 8 showing promising action against dangerous bacteria and fungi. Further research is warranted to explore therapeutic applications of these compounds. [ABSTRACT FROM AUTHOR]

N-nitrosamines (NSAs) and Nitrosamine Drug Substance Related Impurities (NDSRIs) are class of compounds that contains the nitroso functional group. These compounds are carcinogens and mutagens for both humans and animals. As a result, all global regulatory agenesis are requiring risk assessments of NSAs in each pharmaceutical product. The present research aims to provide a single pre-packaged mass spectrometry method parameter set, which includes Ultra performance liquid chromatography and a triple quadrupole mass spectrometer (UPLC-MS-MS) configuration technique for qualifying and quantifying NNHCT in HCT. The analysis was performed on a YMC ODS-A liquid chromatography column with an oven temperature of 35 °C. In this method, mobile phase was prepared by mixing 10 mM ammonium formate buffer and acetonitrile was mixed in the ratio of 60:40 (v/v) with an isocratic program and a flow rate of 0.8 mL/min. The mass detector was used along with electrospray ionization (ESI) Negative mode with multiple reaction monitoring (MRM). The method has been validated in accordance with the current regulatory guidelines and shown the ability to detect NNHCT with a LOQ of 0.01 ppm and LOD of 0.005 ppm. [ABSTRACT FROM AUTHOR]

In this contribution new Cobalt(II), Nickel(II), Copper(II) and Zinc(II) complexes based on the tetradentate ligand [(N1Z,N2Z)-N1,N2-bis((1H-pyrrol-2-yl)methylene)ethane-1,2-diamine] were synthesized and characterized by spectral techniques such as UV–Visible, infrared, nuclear magnetic resonance (NMR, 1H,13C), thermal analysis (DTA and TGA) and mass spectrometry. Results showed that Co (II) and Ni (II) complexes have an octahedral geometry, Zn (II) complex has a tetrahedral structure, and Copper (II) complex has a square planar geometry. Furthermore, based on the molar conductivity values, these complexes were considered as non-electrolytes except the copper complex. The synthesized ligand and their complexes were assessed for their antioxidant and antibacterial activities. All complexes showed greater antioxidant and antibacterial activities with respect to the ligand. In addition, the ligand and its complexes were also tested biologically first on the germination of Lepidium sativum seeds, which is a phytotoxic and antimitotic test, and on the hemolytic and genotoxic behavior of human blood cells. A total inhibition on germination and radicle growth of Lepidium sativum seeds treated with [CuL]Cl22H2O solution was recorded. However, the [CoLCl2]H2O, caused a complete hemolysis of red blood cells and total alteration of nuclei and membranes of leukocytes.

Trimethylamine (TMA) is produced by the intestinal microbiota as a by-product of metabolism of dietary precursors. TMA has been implicated in various chronic health conditions. However, the effect of TMA in the colon and the underlying mechanism was not clear. In this study, TMA exhibited toxic effects in vitro as well as in vivo. TMA-induced oxidative stress causes DNA damage, and compromised cell membrane integrity leading to the release of LDH outside the cells which ultimately leads to cell death. Besides, TMA also exhibited pronounced increase in cell cycle arrest at G2/M phase in both HCT116 and HT29 cell lines. TMA was found to be genotoxic and cytotoxic as the TMA concentration increased from 0.15 mM. A decreased ATP intracellular content was observed after 24 h, 48 h, and 72 h treatment in a time and dose-dependent manner. For in vivo research, TMA (100 mM, i.p. and intra-rectal) once a week for 12 weeks caused significant changes in cellular morphology of colon and rectum epithelium as assessed by H & E staining. TMA also significantly increased the infiltration of inflammatory cells in the colon and rectal epithelium indicating the severity of inflammation. In addition, TMA caused extensive mucosal damage and distortion in the epithelium, decrease in length of small intestine compared to control mice. In conclusion, these results highlight the detrimental effects of TMA in the colon and rectal epithelium.

Bisphenol A (BPA) is one of the most widely used and versatile chemical compounds in polymer additives and epoxy resins for manufacturing a range of products for human applications. It is known as endocrine disruptor, however, there is growing evidence that it is genotoxic. Because of its adverse effects, the European Union has restricted its use to protect human health and the environment. As a result, the industry has begun developing BPA analogues, but there are not yet sufficient toxicity data to claim that they are safe. We investigated the adverse toxic effects of BPA and its analogues (BPS, BPAP, BPAF, BPFL, and BPC) with emphasis on their cytotoxic and genotoxic activities after short (24-h) and prolonged (96-h) exposure in in vitro hepatic three-dimensional cell model developed from HepG2 cells. The results showed that BPFL and BPC (formed by an additional ring system) were the most cytotoxic analogues that affected cell viability, spheroid surface area and morphology, cell proliferation, and apoptotic cell death. BPA, BPAP, and BPAF induced DNA double-strand break formation (γH2AX assay), whereas BPAF and BPC increased the percentage of p-H3-positive cells, indicating their aneugenic activity. All BPs induced DNA single-strand break formation (comet assay), with BPAP (≥0.1 μM) being the most effective and BPA and BPC the least effective (≥1 μM) under conditions applied. The results indicate that not all of the analogues studied are safer alternatives to BPA and thus more in-depth research is urgently needed to adequately evaluate the risks of BPA analogues and assess their safety for humans.

Background: Waterpipe tobacco smoking (WTS) is an issue all over the world, although it is particularly prevalent in the Middle East, and Southeast Asia. The genotoxic effects of smoking were reported to be associated with nucleus abnormalities such as micronuclei (MN), karyorrhexis (KR), karyolysis, pyknosis, binucleates, broken eggs, condensed chromatin in exfoliated buccal mucosal cells, and was believed to be associated with apoptosis of cells and was not correlated to the exposure time. Aim: The aim of this study was to evaluate and compare the cytotoxic and genotoxic effects of cigarette and WTS on buccal mucosa. Materials and Methods: The pertinent search was done through the computerized literature on MEDLINE, EMBASE, and PUBMED databases, which included case-control, clinical and observational studies regarding the mutagenic effects of cigarettes and WTS in oral tissues. The retraction of data in this study was undertaken from May 2010 to May 2022. A total of 60 articles from the search data were retrieved. This investigation was registered with the research center of Riyadh Elm University for institution review board approval (IRB) and obtained the IRB number "FRP/2021/448/733/707 and the systematic review registration number with respect to PROSPERO is 345417. Results: After the removal of duplicates, 32 were evaluated for the inclusion and exclusion criteria. Out of 32 articles, twenty studies were evaluated for cytogenetic abnormalities in buccal mucosal cells of waterpipe tobacco smokers (WTS) and cigarette smokers, and 12 were excluded. The mean MN levels in the oral tissues of WTS were more (1.94 ± 0.39) than in non-smokers (1.68 ± 0.35). Conclusion: Therefore, we conclude that the MN count can be employed as a biomarker and preliminary signal for the identification of changes in oral mucosa among smokers, which develop towards cancer formation. [ABSTRACT FROM AUTHOR]

The goal of this study was to prepare and characterize albumin nanoparticles to be later used as a drug delivery system. The utilization of nanoparticles as a delivery system for antimicrobial drugs has arisen recently which solve many problems and enhance the traditional treatment with this antimicrobial drugs. In this study, nanoparticles of bovine serum albumen were successfully obtained using a coacervation process (separation of proteins in two liquid phases in colloidal systems). The prepared nanoparticles were nearly spherical in shape and have smooth surface as determined by Transmission Electron Microscopy (TEM). The sizes of the obtained nanoparticles were 70 ± 10 nm with negative surface zeta potential. Additionally, the in vitro safety of albumin nanoparticles has been demonstrated. Both cytotoxicity and genotoxicity studies indicated that, there is no observed toxic effect of nano-albumin on lymphocyte cell line. Also, the results showed that the albumin nanoparticles enhances and promotes the response of immune system.

Corn cultivation represents the largest type of agricultural production in Mexico, with great economic, social, and cultural importance. The health of corn producers could be compromised by the extensive and accumulated use of pesticides. The effects of pesticides in terms of their cytotoxic and genotoxic damage in two groups of peasant maize producers in Tlaxcala, Mexico, were considered here. The buccal micronucleus cytome assay was used as an indicator of cytotoxicity and genotoxicity, along with nuclear abnormalities present in farmers who had used pesticides in the last thirty years. In total, 21 commercial products used in corn production were identified, mainly herbicides belonging to the chlorophenoxy, triazine, and organophosphate compounds; in addition, it was observed that a small group of farmers use the active ingredient carbofuran, as well as insecticides and fungicides. The results show that farmers with higher pesticide use present higher rates of cytotoxic and genotoxic damage compared to the group of producers with higher incidence rates of agroecological practices and lower rates of pesticide use, as revealed by the micronucleus assay, as well as by nuclear abnormalities present in the epithelial cells of the buccal mucosa. The agroecological farmer group used only herbicides, with the 2,4-D (Hierbamina) being the greatest use in maize cultivation. [ABSTRACT FROM AUTHOR]

Introduction: Alternative therapies using medicinal plants and herbal medicines have been growing worldwide, as natural treatments have low cost and less toxic effect compared to conventional drugs available. Aim: To evaluate in vitro cytotoxicity and ex-vivo genotoxicity of Brazilian species of the Malvaceae family: Waltheria viscosissima A. St. Hil. In vitro methods were used to verify the cytotoxic potential through hemolytic and antihemolytic assays and the ex-vivo genotoxic analysis. Results: The Crude Etanolic Extract (CEE) and Cloroformic Fraction (CF) was obtained in vegetal sample used on this study; the CEE-Wv and CF-Wv products exhibited the lowest cytotoxic potential with hemolysis less than 40% in all concentrations evaluated. A moderate anti-hemolytic effect was described in all samples treated with 500 and 1000 µg/mL, with hemolysis <60 %. In addition, the compounds showed low ex-vivo genotoxic effect with a general index of normal cells greater than 84 % at all concentrations. Conclusion: The results suggest a low toxic profile of the compounds obtained from species of the Malvaceae family, indicating safe limits for the use of these natural products. [ABSTRACT FROM AUTHOR]

Mammalian sex hormones are steroid-structured compounds that support the growth and development of plants at low concentrations. Since they affect the physiological processes in plants, it has been thought that mammalian sex hormones may cause modifications to plant genomes and epigenetics. This study aims to determine whether different mammalian sex hormones (17 β-estradiol, estrogen, progesterone, and testosterone) in several concentrations (0, 10−4, 10−6, and 10−8 mM) affect genetic or epigenetic levels in bean plants, using in vitro tissue cultures from plumule explants. We investigated levels of DNA damage, changes in DNA methylation and DNA stability in common bean exposed to mammalian sex hormones (MSH) using inter-primer binding site (iPBS) and Coupled Restriction Enzyme Digestion-iPBS (CRED-iPBS) assays, respectively. The highest rate of polymorphism in iPBS profiles was observed when 10−4 mM of estrogen (52.2%) hormone was administered. This finding indicates that genetic stability is reduced. In the CRED-iPBS profile, which reveals the methylation level associated with the DNA cytosine nucleotide, 10−4 mM of estrogen hormone exhibited the highest hypermethylation value. Polymorphism was observed in all hormone administrations compared to the control (without hormone), and it was determined that genomic stability was decreased at high concentrations. Taken together, the results indicate that 17 β-estradiol, estrogen, progesterone, and testosterone in bean plants affect genomic instability and cause epigenetic modifications, which is an important control mechanism in gene expression. [ABSTRACT FROM AUTHOR]

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Genotoxicity is considered as one of the endpoints in assessing toxic effect of pollution. In the present study genotoxic effects of pesticides in the Perna viridis have been evaluated by the induction of micronuclei (MN). The aim of the present study was to assess the MN frequency in the haemolymph of green mussel (Perna viridis) after exposure to different concentrations of organophosphate pesticides (chlorpyrifos, malathion), synthetic pyrethroid pesticide (cypermethrin, lambda-cyhalothrin) and herbicide (buctril). Haemocytes of bivalve play an important role in immune defense and detoxification of contaminants. The bivalves were exposed to different concentrations of test pesticides in a static system. The MN frequencies of all the pesticide treated mussel groups increased significantly (p< 0.05) until the end of the exposure period as compare to control. The highest MN frequencies were recorded after cypermethrin exposure on day 12 (7, 8.5 and 11? for 0.5 ppm, 1 ppm and 1.5 ppm concentrations respectively) in haemolymph. However the lowest MN frequencies were recorded after buctril exposure (3.5, 3.5 and 5? for 0.5 ppm, 1 ppm and 1.5 ppm concentrations, respectively) in haemolymph. The use of haemocytes of green mussel (Perna viridis) in MN assay proved to be a sensitive tool for the assessment of genetic damage. [ABSTRACT FROM AUTHOR]