Mutagenic Effects Research Articles

Mutagenicity and safety evaluation of Ashwagandha (Withania somnifera) root aqueous extract in different models

Withania somnifera (Ashwagandha) also called as Indian ginseng, a revered herb from Indian traditional system of medicine is a rejuvenator and tonic (Rasayana) used for its varied benefits. The roots of ashwagandha exhibit properties like anti-inflammatory, aphrodisiac, anthelmintic, astringent, diuretic, stimulant and thermogenic. However, data of ashwagandha on its mutagenic effects are lacking. In the present study, in-vitro genotoxicity tests were used to evaluate the mutagenic potential of Ashwagandha Root Extract (ARE). Concentrations of 0.156 to 5.00 mg/plate ARE were used for conducting Bacterial reverse mutation test (BRMT). For chromosome aberration (CA) test ARE was used in concentrations of 0.25 to 2.00 mg/ml, and for micronucleus (MN) tests ARE concentrations of 500/1000/2000 mg/kg were used. Acute oral toxicity was conducted in Wistar rats (n = 25) as per the OECD guideline (#423) with doses of 500/1000/2000 mg/kg body weight in male Swiss albino mice for morbidity and mortality for 3 days. The BRMT and CA tests were conducted with and without metabolic activation (S9). The study was approved by the institutional ethics committee (IEC) and institutional animal ethics committee (IAEC). ARE failed to show any mutagenic effects up to a dose of 5 mg/plate in BRMT. Also, ARE did not show any clastogenic activity in doses up to 2 mg/ml in CA test and in micronucleus test up to 2000 mg/kg body weight. These results were observed with and without metabolic activation (S9) under the stated experimental conditions. No mortality, morbidity, or any clinical signs were observed up to 3 days following ARE administration. Ashwagandha root extract failed to show any mortality in doses up to 2000 mg/kg oral dosage and did not show any mutagenic (genotoxic) effects in high concentrations.

Determination of the toxic metabolite aflatoxin M1 in raw, pasteurized and ultra-pasteurized milks comparing the ELISA Technique and High Performance Liquid Chromatography.

Aflatoxins are very potent toxic metabolites with carcinogenic, teratogenic, mutagenic, hepatotoxic and immunosuppressive effects, which constitute a potential risk to human health, so they should be considered as a latent problem that requires continuous examination in order to ensure food quality. This study was carried out with the objective of quantitatively determining the content of Aflatoxin M1 in three types of raw, pasteurized and ultrapasteurized milk consumed in the city of Cuenca-Ecuador, through thecomparative analysis of the High Performance Liquid Chromatography HPLC Techniques, after an extraction process in immunoaffinity columns and the ELISA Technique. Eighty-four samples were analyzed in three types of milk: raw, pasteurized and ultra-pasteurized, with the ELISA technique, none exceeded the detection limit of Aflatoxin M1(125 ppt or 0.125 ppb), established both by the national INEN: 9-10 in force and the parameters established by the Food and Agriculture Organization of the United Nations, Food and Drug Administration of the United States (0.5ppb) and with the High Performance Liquid Chromatography technique, 16 positive samples were found that were between the limit of detection and quantification (0.09 - 0.18 ppb.), obtaining a prevalenceof 19%, so that the High Performance Liquid Chromatography technique is more sensitive in the quantitative detection of the toxic metabolite Aflatoxin M1 in milk.

Assessment of the genotoxic and mutagenic effects induced by T-2 mycotoxin in HepG2 cells

The T-2 toxin is a mycotoxin produced by molds belonging to Fusarium. Among the Fusarium mycotoxins, trichothecenes are frequently reported in food and feed, being the T-2 toxin (T-2) the mycotoxin which possesses the highest toxicity. According to EFSA, T-2 is found in various cereal grains used in food and feed products, mainly in oats, and it has a high environmental impact due to its mechanisms of toxicity. However, recent information on its genotoxic and mutagenic effects is lacking. This work aimed to evaluate the genotoxic and mutagenic potential of T-2 in vitro. For this purpose, HepG2 cells were exposed to 15, 30, and 60 nM T-2 for 24 h, then the DNA damage was evaluated by the micronucleus and the comet assays. In addition, point mutation analysis was performed by the bacterial reverse mutation test using 0.15–60 nM of T-2 concentrations. The results showed chromosomal damage at 60 nM T-2 since significantly more MN appeared at this concentration than in the control samples. Regarding the comet assay, DNA double helix breaks appeared at all concentrations tested and, in a concentration-dependent manner. However, no mutagenic effects were observed at any of the concentrations tested for the Salmonella typhimurium (S. Typhimurium) strains TA98, TA100, TA1535, TA1537, or the Escherichia coli (E. Coli) WP2 strain in the absence or presence of a metabolic activation system. Therefore, these results showed that T-2 mycotoxin produced genotoxic effects by MN and comet assay, while no mutagenicity was observed. However, further research simulating different metabolic activation pathways and the combined exposure of this mycotoxin with other mutagenic chemicals that could be present in the diet is necessary to discard the mutagenic potential of T-2 fully. These results highlight the carcinogenic potential and danger associated with T-2 exposure and should be considered to prevent associated food risks for the human population.

Caenorhabditis elegans as a suitable model to evaluate the toxicity of water from Rolante River, southern Brazil

Abstract Urbanization and agricultural activities increased environmental contaminants. Integrated analysis of water parameters and bioassays represents an essential approach to evaluating aquatic resource quality. This study aimed to assess water quality by microbiological and physicochemical parameters as well as the toxicological effects of water samples on the Ames test and Caenorhabditis elegans model. Samples were collected during (collection 1) and after (collection 2) pesticide application in the upper (S1), middle (S2), and lower (S3) sections of the Rolante River, southern Brazil. Metals were determined by GFAAS and pesticides by UPLC-MS/MS. Bioassays using the Ames test and the nematode C. elegans were performed. Levels of microbiological parameters, as well as Mn and Cu were higher than the maximum allowed limits established by legislation in collection 2 compared to collection 1. The presence of pesticide was observed in both collections; higher levels were found in collection 1. No mutagenic effect was detected. Significant inhibition of body length of C. elegans was found in collection 1 at S2 (P < 0.001) and S3 (P < 0.001) and in collection 2 at S2 (P = 0.004). Comparing the same sampling site between collections, a significant difference was found between the site of collection (F(3,6)=8.75, P = 0.01) and the time of collection (F(1,2)=28.61, P = 0.03), for the S2 and S3 samples. C. elegans model was useful for assessing surface water quality/toxicity. Results suggest that an integrated analysis for the surface water status could be beneficial for future approaches.

Tellimagrandin-I and camptothin a exhibit chemopreventive effects in Salmonella enterica serovar Typhimurium strains and human lymphocytes

ABSTRACT Tellimagrandin-I (TL) and camptothin A (CA) are ellagitannins widely found in diverse plant species. Numerous studies demonstrated their significant biological activities, which include antitumor, antioxidant, and hepatoprotective properties. Despite this protective profile, the effects of TL and CA on DNA have not been comprehensively investigated. Thus, the aim of this study was to determine the mutagenic and antimutagenic effects attributed to TL and CA exposure on Salmonella enterica serovar Typhimurium strains using the Ames test. In addition, the cytotoxic and genotoxic effects were examined on human lymphocytes, employing both trypan blue exclusion and CometChip assay. The antigenotoxic effect was determined following TL and CA exposure in the presence of co-treatment with doxorubicin (DXR). Our results from the Ames test indicated that TL or CA did not display marked mutagenic activity. However, TL or CA demonstrated an ability to protect DNA against the damaging effects of the mutagens 4-nitroquinoline-1-oxide and sodium azide, thereby exhibiting antimutagenic properties. In relation to human lymphocytes, TL or CA did not induce significant cytotoxic or genotoxic actions on these cells. Further, these ellagitannins exhibited an ability to protect DNA from damage induced by DOX during co-treatment, indicating their potential beneficial usefulness as antigenotoxic agents. In conclusion, the protective effects of TL or CA against mutagens, coupled with their absence of genotoxic and cytotoxic effects on human lymphocytes, emphasize their potential therapeutic value in chemopreventive strategies.

Determination of Nylon 66 Microplastics in the Inhalable Fraction of Particulate Matter Using High-Performance Liquid Chromatography – Tandem Mass Spectrometry (HPLC-MS/MS)

Microplastics (MPs) in the air are one of the major concerns due to their possible health risks. In addition, airborne microplastics act as a carrier for several toxic air pollutants and cause carcinogenic, mutagenic and teratogenic effects. Nylon 66 is one of the most abundant MPs in the microenvironments. In this study, we report an optimized method for the quantification of nylon 66 MPs present in the fine particulate matter (PM2.5) using high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS). The optimized method exhibited excellent linearity, recovery rates, intraday and interday precision and sensitivity. The optimized method was deployed to carry out a pilot study to measure the mass concentrations of nylon 66 microplastics present in the inhalable fraction of particulate matter collected in a shopping complex. The observed mass concentrations of nylon 66 MPs in this study are in the range from 0.30 ng m−3 to 4.37 ng m−3. This study demonstrates the presence of inhalable fraction of nylon 66 MPs in the indoor environment and their mass concentrations were determined using HPLC-MS/MS.

Graphitic carbon nitride and its nanocomposites-based sensors for detection of pharmaceutical effluents in food, ecological and biological samples: A mini-review

Pharmaceutical effluents (PEs) have emerged as a global threat to mankind owing to their adverse health effects on humans. Generally, PEs are acquainted with the environment via direct emissions from drug manufacturing plants, unplanned disposal of unused or expired medicines, unprocessed patient/animal excretion, aquafarming, etc. Unlike other pollutions, PE-based contaminations can lead to catastrophic consequences via genotoxic, ecotoxicological, mutagenic effects, etc., causing behavioural changes, reproductive damage, and chronic damage. Therefore, a susceptible detection platform for PE traces in different sources like water bodies, human biofluids, etc., is in high demand. Owing to their high surface area, chemical stability, and electrocatalytic activity, the 2D graphitic carbon nitride (gCN) has gathered significant research interest. It has been examined for the electrochemical detection of PE traces in different ecological and biological samples. In this mini-review, we discuss the exciting advancements in the design and fabrication of gCN and its nanocomposite-based electrochemical sensors for other trace-level detection of different PEs in ecological and biological systems. The table in this review provides a clear insight into the reported gCN-based electrochemical sensors and their performance analysis towards sensing of EFs. The anticipated developments are discussed with current limitations in gCN-based electrochemical sensors for PE detection.

Trihalomethanes in developed and developing countries.

The reactions between natural organic matter, anthropogenic contaminants, ions, and disinfectants lead to the formation of disinfection by-products (DBPs) such as trihalomethanes (THMs) in drinking water. The formation of THMs is strongly related to the chlorination of water. The study's central objective was to compare the concentration of THMs in twenty developed and developing countries and their disinfection techniques. The THM concentration in 11 developed and 9 developing countries ranged from 0.5 µg/L (Germany) to 215 µg/L (Russia) and 3 µg/L (China) to 439.2 µg/L (Bangladesh), respectively. The developed country has partially succeeded in reducing THM concentration in drinking water, whereas significant steps are needed in developing countries to reduce the existing high THM concentration. The concentration of THMs in water varies among these countries because of the different water sources, water quality, environmental conditions, and efficiency of water treatment technologies. A meaningful relationship has been observed between the properties of water and the THM formation. The use of chemical disinfectants will result in new forms of DBPs that are undesirable due to their carcinogenic and mutagenic effects on human health. The DBP guidelines by various national and international agencies have helped to control and manage the THM concentration in drinking water. However, these regulatory standards are not continuously monitored. Therefore, the formation of these compounds should be prevented either by removing THMs forming precursors or by using an integrated approach for controlling THM formation by implementing advanced water treatment technology. Extensive research is desirable in domains like THM minimization strategies which are easy to deploy, scalable, and cost-effective.

Occupational carcinogens and mutagens in Poland - occurrence and workers' exposure in the years 2018-2021 based on the data from Central register of carcinogenic or mutagenic agents

Central register of data on exposure to carcinogenic or mutagenic chemical substances, their mixtures, agents or technological processes (CRCR) conducted by Nofer Institute of Occupational Medicine (NIOM) enables monitoring of such agents occurrence in working environment in Poland. The NIOM conducts CRCR based on the provisions of the Regulation of the Minister of Health of 24 July 2012 on chemical substances, their mixtures, agents or technological processes with carcinogenic or mutagenic effects in the work environment. The work summarizes the information reported to CRCR in 2018-2021. The data were extracted from CRCR, to which it was transferred by sanitary inspections. The data were extracted from CRCR. Data in this register is gathered based on employers' notifications to sanitary inspection. The study includes the number of reported agents (chemical substances and technological processes), the number of enterprises and the number of persons exposed to particular groups of agents (chemical substances, technological processes, ionizing radiation). The number of substances notified to the CRCR increases, from 382 reported substances in 2018 to 444 in 2021. Significant increase in the number of enterprises reporting technological processes (from 981 in 2018 to 5422 in 2021) and the number of exposed persons results from the law amendments extending the list of carcinogenic or mutagenic processes. The CRCR is a unique database on the occurrence and exposure to occupational carcinogens and mutagens, in which data from over 20 years has been collected. The increase in the number of reports to the register was mainly influenced by legislative changes regarding carcinogenic or mutagenic agents. Due to amount and complexity of data, they can be used for analysis in projects and programs aimed at raising awareness and reducing risk of occupational exposure to carcinogens and also during legislative works in Poland and in the EU. Med Pr Work Health Saf. 2023;74(5):399-407.

IMPACT OF HAZARDOUS TOXIC FACTORS OF FIRES DURING MILITARY ACTIONS ON ECOSYSTEMS AND POPULATION LIFE ACTIVITIES

It has been analysed that wildfires are the most influential factor in environmental pollution. The ecological consequences of wildfires consist primarily of atmospheric air pollution with carbon monoxide, products of combustion of combustible materials, and the burning of oxygen. Plant combustion also contributes significantly to planetary environmental changes: climate warming, ozone depletion, acid rain, chemical and radioactive pollution of the atmosphere, water, and soil. With wildfires, soot particles, that is, carbon and products of incomplete combustion of wood, enter the air. Smoke, which is formed during fires, explosions, ignitions, etc., during the combustion of plant biomass (grasses, leaves from trees and shrubs, mosses, lichens, peatlands, forest litter and needles), is an aerosol-gas mixture containing hazardous substances dangerous to the environment and humans. Biomass burning is a global source of gas and dust pollution of the atmosphere and is considered one of the determining factors of ecotoxicological risks for public health. The negative impact of fires from military actions on the human body is acute and delayed. Acute exposure leads to hypoxia due to carbon oxides, increased consumption of oxygen from the air during combustion, irritation of the respiratory tract, and difficulty breathing. Delayed exposure is due to toxic, mutagenic, and carcinogenic effects. The toxic impact of fires on the life and health of the population is not only a threat to life but also an adverse effect on human organisms of heavy compounds of chemical substances represented by the combustion products of plant biomass of forests, peatlands, vast agricultural lands, including crop rotations and pastures. Often, this impact occurs in combination with typical atmospheric air pollution: emissions from industrial enterprises and motor vehicles. The peculiarity of such a combination is the complex synergistic effects of chemical compounds and high air temperature with significant relative duration (decades, months) of emergency environmental situations. Keywords: toxic factors, fires, ecosystem, human activity.

New insights into the typical nitrogen-containing heterocyclic compound-quinoline degradation and detoxification by microbial consortium: Integrated pathways, meta-transcriptomic analysis and toxicological evaluation

As the primary source of COD in industrial wastewater, quinoline has aroused increasing attention because of its potential teratogenic, carcinogenic, and mutagenic effects in the environment. The activated sludge isolate quinoline-degrading microbial consortium (QDMC) efficiently metabolizes quinoline. However, the molecular underpinnings of the degradation mechanism of quinoline by QDMC have not been elucidated. High-throughput sequencing revealed that the dominant genera included Diaphorobacter, Bacteroidia, Moheibacter and Comamonas. Furthermore, a positive strong correlation was observed between the key bacterial communities (Diaphorobact and Bacteroidia) and quinoline degradation. According to metatranscriptomics, genes associated with quorum sensing, ABC transporters, component systems, carbohydrate, aromatic compound degradation, energy metabolism and amino metabolism showed high expression, thus improving adaptability of microbial community to quinoline stress. In addition, the mechanism of QDMC in adapting and resisting to extreme environmental conditions in line with the corresponding internal functional properties and promoting biogegradation efficiency was illustrated. Based on the identified products, QDMC effectively mineralized quinoline into low-toxicity metabolites through three major metabolic pathways, including hydroxyquinoline, 1,2,3,4-H-quinoline, 5,6,7,8-tetrahydroquinoline and 1-oxoquinoline pathways. Finally, toxicological, genotoxicity and phytotoxicity studies supported the detoxification of quinoline by the QDMC. This study provided a promising approach for the stable, environmental-friendly and efficient bioremediation applications for quinoline-containing wastewater.

Mutagenic effect of ultraviolet rays on sex expression in summer squash genotypes

The present study aimed to induce genetic variations within the control of sex expression in summer squash using ultraviolet rays (UV) as a physical source of mutations in plants. Because the sex expression in summer squash is fundamentally controlled mainly by genetics and partially by the environment. Therefore, this study tries to increase floral differentiation of female flowers, as well as decrease male flowers developed per plant, because summer squash usually exhibit more male flowers and lower female flowers. This will cause decreases in fruits yield per plant. This study was designed in a randomized complete block design with a factorial investigation. It was included four genotypes of summer squash subjected to four exposure periods of UV rays, with three repetitions for each experimental unit. The results showed that genotype number four increased the features of female flowers by 28% and 14% at 4 and 8 minutes of exposure period, respectively. The 12 – minute exposure period significantly increased floral differentiation among all genotypes toward male flowers developed per plant. Meanwhile, genotype number two enhanced floral differentiation toward female flowers by 14% at 8 minutes of exposure period, indicating that these few periods of exposure to UV irradiation may be responsible for induced benefit mutations in cucurbits affected on sex expression, as it induced high number of female flowers. The results indicated that UV irradiation had a direct role in promoting floral differentiation as it inducement higher female flowers in some genotypes leading to improve floral characteristics, as a consequence increased fruits yield per plant.

Unlocking the potential of aromatase inhibitors: recent advances in drug design, synthesis, docking activity, and in vitro bioactivity evaluations

Breast cancer, a global health concern claiming approximately 685,000 lives in 2020, necessitates continual advancements in therapeutic strategies. Estrogen and aromatase play pivotal roles in hormone-responsive breast cancer, with 80% of patients exhibiting estrogen receptor-positive tumors. Aromatase inhibitors (AIs), notably non-steroidal inhibitors like anastrozole and letrozole, have significantly improved outcomes, yet challenges persist, including side effects. This review focuses on recent developments in AIs, exploring xanthone derivatives, imidazole derivatives, and curcumin derivatives as potential inhibitors of aromatase. Molecular docking studies, employing Auto Dock and other tools, reveal the binding affinities and interactions of these compounds with the aromatase enzyme. Among xanthones, Erythrommone emerges as a potent inhibitor, holding promise for clinical trials. Imidazole derivatives, synthesized through the Debus-Radziszewski reaction, demonstrate anticancer potential, with compounds like 1a exhibiting superior efficacy against MCF7 cells. ADME-Tox analyses indicate promising drug-likeness but reveal potential mutagenic effects and environmental impacts. Curcumin derivatives, particularly 1,5-diaryl-1,4-pentadien-3-ones, present alternatives to address curcumin's bioavailability challenges. A study of 25 compounds (DKC) identifies DKC-10 as a potent inhibitor, outperforming established breast cancer drugs in terms of binding affinity and interactions with aromatase and ERα+ receptors. These findings underscore the importance of exploring diverse chemical structures in developing AIs, paving the way for more effective and well-tolerated therapeutics. The integration of computational techniques, such as molecular docking studies, accelerates drug discovery by predicting interactions at the molecular level. Overall, this comprehensive review provides valuable insights into the evolving landscape of aromatase inhibitors, offering a roadmap for future research and the development of advanced breast cancer therapeutics.

Genotoxic and Mutagenic Assessment of PT-31, a Molecule with Antipsychotic Potential

Abstract: The PT-31 molecule, a potential antipsychotic, has demonstrated promising results when orally administrated to in vivo models. A recent study suggested the genotoxic and mutagenic po-tential of PT-31 after acute treatment by intraperitoneal route. This study aimed to evaluate PT-31 potential of inducing genotoxic or mutagenic damage after acute oral administration. For that, adult males and females Balb/C mice were treated acutely by oral administration with vehicle or PT-31 in three different doses (10, 20, and 40 mg kg-1). After 24 hours from PT-31 administration, animals were euthanized for performing the comet and micronucleus assays. None of the tested groups of PT-31 presented a significant increase in damage index and MN frequency. However, they presen-ted the following tendency on damage index: females presented a tendency at 40 mg kg-1 and males at 20 mg kg-1. Regarding the MN assay, male mice at the highest dose of 40 mg kg-1 presented a tendency of increased MN frequency. Also, there was a significant increase in PCE/NCE ratio in male mice. Results suggest that the male mice group presented higher susceptibility to damage. The tendency of increased damage to DNA and MN frequency suggests that the molecule PT-31 may induce reparable damage to DNA, and these DNA strand repairs may have originated from the MN. However, significant genotoxic and mutagenic effects were not observed. This study reinforces the atypical profile of the molecule as much as its safety by oral route administration.

A mutation rate model at the basepair resolution identifies the mutagenic effect of polymerase III transcription.

De novo mutations occur at substantially different rates depending on genomic location, sequence context and DNA strand. The success of methods to estimate selection intensity, infer demographic history and map rare disease genes, depends strongly on assumptions about the local mutation rate. Here we present Roulette, a genome-wide mutation rate model at basepair resolution that incorporates known determinants of local mutation rate. Roulette is shown to be more accurate than existing models. We use Roulette to refine the estimates of population growth within Europe by incorporating the full range of human mutation rates. The analysis of significant deviations from the model predictions revealed a tenfold increase in mutation rate in nearly all genes transcribed by polymerase III (Pol III), suggesting a new mutagenic mechanism. We also detected an elevated mutation rate within transcription factor binding sites restricted to sites actively used in testis and residing in promoters.

Polycyclic aromatic hydrocarbons in the sediments of highly polluted coastal area in the Red Sea: levels, spatial distribution, and risk assessment.

The southern part of the Jeddah coast faces a range of pollution challenges that can impact the water quality and ecosystem in the area. Pollution sources are represented mainly by treated wastewater (TWW), harbor activities, and atmospheric deposition from vehicle exhaustemissions. Polycyclic aromatic hydrocarbons (PAHs) are among the persistent organic pollutants that interfere with all environmental matrices and could cause humane mutagenic and carcinogenic effects. In the present study, 16 priority parent and 21 methylated PAHs (∑37PAHs) were assessed in the sediments of three hot spot coastal sites (Islamic Jeddah port, Al-Arbaeen, and Al-Shabab lagoons) to evaluate the factors affecting their spatial distribution, examine their probable sources and potential adverse effects. The total detected concentrations of ∑37PAHs ranged from 785.9 to 8359.8ng/g dw (average: 2296.3 ± 2017.3ng/g dw). The highest levels of ∑37PAHs were detected near TWW stations. The highest individual PAH congeners observed were phenanthrene, anthracene, and pyrene. PAH molecular diagnostic ratios pointed out different pyrogenic sources. In some specific stations, there was an overlap of petrogenic origin. The sediment samples contained high concentrations of methylated PAHs, with concentrations ranging from 558.42 to 6321.21ng/g dw and an average concentration of 1679.1 ± 1430.7ng/g dw. The sediment quality guidelines indicated that adverse biological effects are likely to occur at least at the two TWW disposal stations and the sediments in these stations are at risk. The values of the mutagenic equivalence quotient (MEQ) and toxic equivalence quotient (TEQ) of carcinogenic PAHs were recorded at 39.88 and 33.17ng/g, respectively.

Determination of biochemical and histopathological changes on testicular and epididymis tissues induced by exposure to insecticide Imidacloprid during postnatal development in rats

BackgroundImidacloprid is a neonicotinoid insecticide belonging to the chloronicotinyl nitroguanidine chemical family. Toxicity of IMD for mammals in scientific studies has shown high mutagenic, immunotoxic, teratogenic and neurotoxic effects. The present study was designed to assess the toxic effects of imidacloprid (IMD) on the testicular and epididymis tissues as well as testosterone levels of neonatal male rats.MethodsNeonatal male rats from postnatal day (PND) 1 to PND 26 were consecutively administered with different concentrations of IMD (1, 5 and 10 mg/kg) subcutaneously. The effect of IMD on body and organ weight, lipid profile, histopathological alterations, oxidative stress and altered testosterone levels were assessed in the testis and plasma.ResultsThe results of body weight gain showed a significant difference in group 4 (10 mg/kg) animals as compared to the control. A significant increase in total cholesterol and triglycerides, while a decrease in high-density lipoprotein concentrations was evident. Similarly, a significant decrease in concentrations of antioxidant enzymes (CAT and SOD) among all the IMD-treated groups was evident, when compared to the control. Increased production of ROS was also noticed in the highest-dose treatment group. Further, we observed that IMD-treated rats indicated histopathological changes in the testis and epididymis along with a significant decrease in the plasma testosterone concentrations among IMI-treated groups in contrast to the control. Histological examination of the testis of IMD-treated neonatal male rats also showed decreased spermatogenesis in the treated groups when compared to the control. Furthermore, an increase in lumen diameter and a decrease in epithelial height of seminiferous tubules were also observed in IMD-treated rats in comparison with the control.ConclusionIt is concluded that sub-chronic exposure to IMD in neonatal male rats may induce histopathological changes in reproductive tissues and damage normal testicular functions via inducing oxidative stress, decrease in body weight, disturbing normal blood lipid profile and testosterone concentration. IMD exposure can induce pathophysiological effects calls for further evaluation of this widely used insecticide.

Glyoxal acid-free (GAF) histological fixative is a suitable alternative to formalin: results from an open-label comparative non-inferiority study

Formalin, an aqueous solution of formaldehyde, has been the gold standard for fixation of histological samples for over a century. Despite its considerable advantages, growing evidence points to objective toxicity, particularly highlighting its carcinogenicity and mutagenic effects. In 2016, the European Union proposed a ban, but a temporary permission was granted in consideration of its fundamental role in the medical-diagnostic field. In the present study, we tested an innovative fixative, glyoxal acid-free (GAF) (a glyoxal solution deprived of acids), which allows optimal tissue fixation at structural and molecular level combined with the absence of toxicity and carcinogenic activity. An open-label, non-inferiority, multicentric trial was performed comparing fixation of histological specimens with GAF fixative vs standard phosphate-buffered formalin (PBF), evaluating the morphological preservation and the diagnostic value with four binary score questions answered by both the central pathology reviewer and local center reviewers. The mean of total score in the GAF vs PBF fixative groups was 3.7 ± 0.5 vs 3.9 ± 0.3 for the central reviewer and 3.8 ± 0.5 vs 4.0 ± 0.1 for the local pathologist reviewers, respectively. In terms of median value, similar results were observed between the two fixative groups, with a median value of 4.0. Data collected indicate the non-inferiority of GAF as compared to PBF for all organs tested. The present clinical performance study, performed following the international standard for performance evaluation of in vitro diagnostic medical devices, highlights the capability of GAF to ensure both structural preservation and diagnostic value of the preparations.

Genotoxic and Mutagenic Effects of the Alternaria Mycotoxin Alternariol in Combination with the Process Contaminant Acrylamide.

Humans are constantly exposed to mixtures of different xenobiotics through their diet. One emerging concern is the Alternaria mycotoxin alternariol (AOH), which can occur in foods typically contaminated by the process contaminant acrylamide (AA). AA is a byproduct of the Maillard reaction produced in carbohydrate-rich foods during thermal processing. Given the genotoxic properties of AOH and AA as single compounds, as well as their potential co-occurrence in food, this study aimed to assess the cytotoxic, genotoxic, and mutagenic effects of these compounds in combination. Genotoxicity was assessed in HepG2 cells by quantifying the phosphorylation of the histone γ-H2AX, induced as a response to DNA double-strand breaks (DSBs). Mutagenicity was tested in Salmonella typhimurium strains TA98 and TA100 by applying the Ames microplate format test. Our results showed the ability of AOH and AA to induce DSBs and increase revertant numbers in S. typhimurium TA100, with AOH being more potent than AA. However, no synergistic effects were observed during the combined treatments. Notably, the results of the study suggest that the compounds exert mutagenic effects primarily through base pair substitutions. In summary, the data indicate no immediate cause for concern regarding synergistic health risks associated with the consumption of foods co-contaminated with AOH and AA.

Toxicological assessment of minoxidil: A drug with therapeutic potential besides alopecia

Minoxidil is regularly prescribed for alopecia, and its therapeutic potential has expanded in recent times. However, few studies have been conducted to evaluate its toxicity, and controversial findings regarding its mutagenic activities remain unsolved. This study aimed to access cytotoxic, genotoxic, and mutagenic properties of minoxidil using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay, comet assay, and micronucleus test in mouse fibroblast (L929) cells and its point mutation induction potential in the Salmonella/microsome assay. Furthermore, an in vivo toxicity assessment was conducted in Caenorhabditis elegans. Minoxidil showed cytotoxicity at 2.0 mg/mL in MTT assay. Genotoxicity was observed after 3 h treatment in L929 cells using comet assay. No mutagenic effect was observed in both the micronucleus test and the Salmonella/microsome assay. The lethal dose 50 in C. elegans was determined to be 1.75 mg/mL, and a delay in body development was detected at all concentrations. In conclusion, minoxidil induces DNA damage only in early treatment, implying that this DNA damage may be repairable. This observation corroborates the absence of mutagenic activities observed in L929 cells and Salmonella typhimurium strains. However, the toxicity of minoxidil was evident in both C. elegans and L929 cells, underscoring the need for caution in its use.