Oxidative stress and DNA alteration on the earthworm Eisenia fetida exposed to four commercial pesticides.

Modern agriculture is mainly based on the use of pesticides to protect crops but their efficiency is very low, in fact, most of them reach water or soil ecosystems causing pollution and health hazards to non-target organisms. Fungicide triazoles and strobilurins based are the most widely used and require a specific effort to investigate toxicological effects on non-target species. This study evaluates the toxic effects of four commercial fungicides Prosaro® (tebuconazole and prothioconazole), Amistar®Xtra (azoxystrobin and cyproconazole), Mirador® (azoxystrobin) and Icarus® (Tebuconazole) on Eisenia fetida using several biomarkers: lipid peroxidation (LPO), catalase activity (CAT), glutathione S-transferase (GST), total glutathione (GSHt), DNA fragmentation (comet assay) and lysozyme activity tested for the first time in E. fetida. The exposure to Mirador® and AmistarXtra® caused an imbalance of ROS species, leading to the inhibition of the immune system. AmistarXtra® and Prosaro®, composed of two active ingredients, induced significant DNA alteration, indicating genotoxic effects. This study broadened our knowledge of the effects of pesticide product formulations on earthworms and showed the need for improvement in the evaluation of toxicological risk deriving from the changing of physicochemical and toxicological properties that occur when a commercial formulation contains more than one active ingredient and several unknown co-formulants.

Allium cepa tests: Exploring bleomycin induced cyto-genotoxicity and altered cell cycle kinetics in root tips meristematic cells.

Bleomycin, commonly employed in treating Hodgkin's lymphoma and testicular cancer, is associated with significant pulmonary toxicity. While various studies have assessed the toxic impact of chemotherapeutic agents on aquatic and terrestrial environments, limited data exist on bleomycin's effects, especially concerning higher plants. To address this gap, we utilized the Allium cepa assays, renowned for evaluating chemical and biochemical agents' toxic effects, to investigate bleomycin's impact on the terrestrial ecosystem. Our study aimed to assess bleomycin's cyto-genotoxic effects on A. cepa root tip cells at minimal concentrations (10-40 µg mL-1) and varied exposure durations (2, 4, 6, and 24 h). Analysis of nuclear and mitotic abnormalities in bleomycin-treated A. cepa root tip cells, alongside an acridine orange-ethidium bromide double staining assay, illuminated its influence on cell viability. Additionally, agarose gel electrophoresis determined the drug's potential for DNA degradation, unveiling the underlying mechanisms of cyto-genotoxicity. Results also demonstrated a decline in the mitotic index with increased bleomycin concentrations and exposure time, elevated frequencies of various cyto-genotoxic abnormalities, including sticky chromosomes, chromatid breaks, laggards, bridges, polar deviations, nuclear lesions, and hyperchromasia. The study indicated the potential risks of bleomycin even at low concentrations and brief exposures, highlighting its severe adverse effects on genetic material of plant, potentially contributing to cell death. Consequently, this investigation unveils bleomycin's cyto-genotoxic effects on higher plant system, underscoring its threat to terrestrial ecosystems, particularly upon chronic and unmonitored exposure.

Impact of Schistosoma sp., Infection on Biological, Feeding, Physiological, Histological, and Genotoxicological Aspects of Biomphalaria alexandrina and Bulinus truncatus Snails.

BACKGROUND: Trematode infections of the genus Schistosoma can induce physiological and behavioral changes in intermediate snail hosts. This is because the parasite consumes essential resources necessary for the host's survival, prompting hosts to adapt their behavior to maintain some level of fitness before parasite-induced mortality occurs. METHODS: In this study, the reproductive and biochemical parameters of Biomphalaria alexandrina and Bulinus truncatus were examined during the cercareal shedding stage of infection with Schistosoma mansoni and Schistosoma haematobium, respectively, compared with controls. RESULTS: The study revealed an infection rate of 34.7% for S. mansoni and 30.4% for S. haematobium. In B. alexandrina infected with S. mansoni, a survival rate of 65.2% was recorded, along with a mean prepatent period of 30.3 ± 1.41 days, a mean shedding duration of 14.2 ± 0.16 days, and a mean lifespan of 44.1 ± 0.24 days. Meanwhile, in B. truncatus infected with S. haematobium, a survival rate of 56.4% was observed, with a mean prepatent period of 44.3 ± 1.41 days, a mean shedding duration of 22.6 ± 2.7 days, and a mean lifespan of 66.9 ± 1.6 days. Feeding increased in both infected species of snails, while the net reproductive rate (Ro) of the infected snails decreased. Total antioxidant (TAO) and lipid peroxidation activity increased in the two infected snail species during shedding, while Glutathione-S-transferase levels decreased. Lipid peroxidase activity and nitrogen oxide levels significantly decreased in infected B. alexandrina and increased in infected Bulinus. Steroid hormone levels were elevated in infected Biomphalaria, whereas they were reduced in infected Bulinus. Comet assay parameters showed an increase in the two infected genera after infection compared to control snails, indicating genotoxic damage and histopathological damage was observed. CONCLUSIONS: These findings demonstrate that infection with larva species diverse biochemical, hormonal, genotoxic, and histopathological changes in the tissues responsible for fecundity and reproduction in B. alexandrina and B. truncates comparing with controls.

Secreted cyclophilin A is non-genotoxic but acts as a tumor promoter.

Chronic inflammation is associated with malignant transformation and creates the microenvironment for tumor progression. Cyclophilin A (CypA) is one of the major pro-inflammatory mediators that accumulates and persists in the site of inflammation in high doses over time. According to multiomics analyses of transformed cells, CypA is widely recognized as a pro-oncogenic factor. Vast experimental data define the functions of intracellular CypA in carcinogenesis, but findings on the role of its secreted form in tumor formation and progression are scarce. In the studies here, we exploit short-term in vitro and in vivo tests to directly evaluate the mutagenic, recombinogenic, and blastomogenic effects, as well as the promoter activity of recombinant human CypA (rhCypA), an analogue of secreted CypA. Our findings showed that rhCypA had no genotoxicity and, thus, was neither involved in nor influenced the initiation stage of carcinogenesis. At high doses, rhCypA could disrupt gap junctions in rat liver epithelial IAR-2 cells in vitro by decreasing the expression of connexins 26 and 43 in these cells and inhibit A549 cell adhesion. These data suggested that rhCypA could contribute to epithelial-mesenchymal transition in malignant cells. The research presented here elucidated the role of secreted CypA in carcinogenesis, revealing that it is not a tumor initiator but can act as a tumor promoter at high concentrations.

In vitro cytogenotoxic evaluation of aripiprazole on human peripheral lymphocytes and computational molecular docking analysis.

Two different drug groups, typical (classic) and atypical (new), are used in the treatment of schizophrenia. Aripiprazole, an atypical antipsychotic chemical, is the active ingredient of the drug Abilify. This study was conducted to determine the possible genotoxic effect of aripiprazole. For this purpose, four different doses of aripiprazole (5; 10; 20, and 40 µg/mL) were examined with Chromosome Abnormality (CA), Sister Chromatid Exchange (SCE), Micronucleus (MN) tests. Based on these tests, Proliferation Index (PI), Percent Abnormal Cells (AC), Mitotic Index (MI), Micronuclear Binuclear Cell (MNBN), and Nuclear Division Index (NDI) levels were determined in human peripheral lymphocytes treated for 24 and 48 hours. Also, to determine possible binding sites of Aripiprazole on B-DNA molecular docking analysis was performed using AutoDock 4.0 (B-DNA dodecamer, PDB code: 1BNA). Aripiprazole binds to B-DNA with a very significant free binding energy (-11.88 Kcal/mol). According to our study, aripiprazole did not significantly change SCE, CA, AC percentage, MN frequencies when compared with control. According to these results, aripiprazole does not have a genotoxic effect. At the same time, no significant change was observed in the PI, MI, and NDI frequencies when compared with the control. In line with these results, it was observed that the use of aripiprazole in the treatment of schizophrenia did not pose any acute genotoxic and cytotoxic risk.

Genotoxicity, Cytotoxicity and Phenolic Compounds from Aqueous Extracts of Phyllanthus tenellus Roxb. Cultivated Under Different Light Conditions.

<b>Background and Objective:</b> <i>Phyllanthus tenellus</i> Roxb. is a medicinal species widely used in Brazil for diseases of the urinary tract, kidney stones, infections and as a diuretic. The therapeutic property of this species is due to the production of phenolic compounds by secondary metabolism. However, cultivation conditions can alter the production of phenolic compounds and compromise the medicinal use of the species. The aim of this research was the evaluation of the genotoxic and cytotoxic activity of aqueous extracts of the species <i>Phyllanthus tenellus</i> Roxb. grown with and without shading, on the <i>Allium cepa</i> cell cycle and also, determine the phenolic compounds present in the aqueous extracts in each of the cultivation conditions. <b>Materials and Methods:</b> For the <i>Allium cepa</i> test three concentrations of 5, 10 and 15 g L¹ of the aerial part of the plant were used for the preparation of aqueous extracts, referring to the two forms of cultivation, with and without shading. <b>Results:</b> The aqueous extracts of <i>Phyllanthus tenellus</i> Roxb. have cytotoxic activity, except for the 5 g L¹ concentration of the cultivation with shading, which is the only concentration that has a genotoxic effect. <b>Conclusion:</b> The incidence of light stimulates the increase in the concentration of phenolic compounds (total polyphenols, flavonoids and tannins) in the species when cultivated in full sun.

Toxicological impact of organophosphorus Chlorpyrifos 48%EC pesticide on hemocytes, biochemical disruption, and molecular changes in Biomphalaria alexandrina snails.

Organophosphorus pesticides like Chlorpyrifos 48%EC were widely used to control agricultural pests. The present study aimed to evaluate the toxic effects of Chlorpyrifos 48%EC on B. alexandrina snails, the intermediate host of Schistosoma mansoni. After exposure of snails to serial concentrations to determine the LC50, thirty snails for each sublethal concentration (LC10 2.1 and LC25 5.6 mg/l) in each group were exposed for 24 h followed by another 24 h for recovery. After recovery random samples were collected from hemolymph and tissue to measure the impacts on Phagocytic index, histological, biochemical, and molecular parameters. The current results showed a toxic effect of Chlorpyrifos 48%EC on adult B. alexandrina snails after 24 h of exposure at LC50 9.6 mg/l. After exposure to the sub-lethal concentrations of this pesticide, it decreased the total number of hemocytes and the percentage of small cells, while increased the percentage of hyalinocytes. The granulocyte percentage was increased after exposure to LC10, while after LC25, it was decreased compared to the control group. Also, the light microscopical examination showed that some granulocytes have plenty of granules, vacuoles and filopodia. Some hyalinocytes were contained shrinked nuclei, incomplete cell division and forming pseudopodia. Besides, the phagocytic index of hemocytes was significantly increased than control in all treated groups. Also, these sub-lethal concentrations increased MDA and SOD activities, while, tissue NO, GST and TAC contents were significantly decreased after exposure. Levels of Testosterone (T) and Estradiol (E) were increased significantly after exposure compared with control group. The present results showed that the concentration of DNA and RNA was highly decreased after exposure to LC10, 25 than the control group. Therefore, B. alexandrina snails could be used as a bio monitor of the chemical pollution. Besides, this pesticide could reduce the transmission of schistosomiasis as it altered the biological system of these snails.

Brain injury, genotoxic damage and oxidative stress induced by Bromuconazole in male Wistar rats and in SH-SY5Y cell line.

BACKGROUND: Bromuconazole is a widely used triazole against various fungi disease. It's employment provokes harmful effects on the environment and human health. In the present study, we explored bromuconazole toxic effects in both rat brain tissue and SH-SY5Y cell line. METHODS: Male Wistar rats were administrated orally with Bromuconazole (NOEL/4, NOEL o and NOEL ×2) daily for consecutive 28 days. In addition, neuronal SH-SY5Y cell line was used. The rat brains and SH-SY5Y cells were collected and analysed for AChE activity, oxidative stress biomarkers, genotoxicity and histopathological alterations. RESULTS: Our results showed that rat exposure to bromuconazole at doses corresponding to NOEL/4, NOEL and NOEL ×2 caused brain histopathological alteration and decrease in acetylcholine esterase (AChE) activity. In SH-SY5Y cell line, bromuconazole strongly induced cell mortality with an IC50 about 250 µM. Bromuconazole induced also DNA damage as assessed by comet assay in both rat brain tissue and SH-SY5Y cell. Moreover, bromuconazole increased ROS production, malondialdehyde (MDA) and protein carbonyl (PC) levels and enhanced the enzymatic activities of catalase (CAT), superoxide dismutase (SOD), Glutathione-S-transferase (GST) and peroxidase (GPx) in the two studied systems. CONCLUSION: Therefore, we can deduce that bromuconazole-caused neurotoxicity may be related to oxidative statue disturbance.HIGHLIGHTSBromuconzole causes oxidative stress in the brain tissue of male Wistar rats.Bromuconazole enhances MDA, PC levels and induces DNA damage in rat brain.Bromuconazole provokes disturbance of the neuronal antioxidant system.Bromuconazole induces histopathological alterations in rat brain.Bromuconazole exposure induced cytotoxic effects and DNA damage in SH-SY5Y cells.Bromuconazole exposure induced oxidative stress in SH-SY5Ycells.

Bromuconazole caused genotoxicity and hepatic and renal damage via oxidative stress process in Wistar rats.

Bromuconazole is a triazole pesticide used to protect vegetables and fruits against diverse fungi pathologies. However, its utilization may be accompanied by diverse tissue injuries. In this study, we evaluated the biochemical and histopathological modifications, and we analyzed genotoxic and oxidative stress, in the aim to examine bromuconazole effects in the liver and kidney. We subdivided animals into four groups, each one contains six adult male Wistar rats. Untreated rats received daily a corn oil (vehicle) orally. Three oral bromuconazole doses were tested (1, 5, and 10 % of LD50) daily for 28 days. Bromuconazole increased the plasma activities of alkaline phosphatase, lactate dehydrogenase, and transaminases. It also increased the plasma levels of creatinine and uric acid. Histopathological check showed that bromuconazole caused organ damage. This study makes known that bromuconazole caused conspicuous DNA damage either in hepatic or kidney tissues, with a significant increase in the levels of malondialdehyde and protein carbonyl followed by an enhancement in catalase and superoxide dismutase enzymatic activities, and these increases are in a dose-dependent manner. In other side, we found that Glutathione-S-transferase and peroxidase activities raised. Our outcomes highlight that bromuconazole exposure induced genotoxic damage and organ damage which may be caused by the disturbances of oxidative stress statue in the liver and kidney.

Interferon α2-Thymosin α1 Fusion Protein (IFNα2-Tα1): A Genetically Engineered Fusion Protein with Enhanced Anticancer and Antiviral Effect.

Human interferon α2 (IFNα2) and thymosin α1 (Tα1) are therapeutic proteins used for the treatment of viral infections and different types of cancer. Both IFNα2 and Tα1 show a synergic effect in their activities when used in combination. Furthermore, the therapeutic fusion proteins produced through the genetic fusion of two genes can exhibit several therapeutic functions in one molecule. In this study, we determined the anticancer and antiviral effect of human interferon α2-thymosin α1 fusion protein (IFNα2-Tα1) produced in our laboratory for the first time. The cytotoxic and genotoxic effect of IFNα2-Tα1 was evaluated in HepG2 and MDA-MB-231 cells. The in vitro assays confirmed that IFNα2-Tα1 inhibited the growth of cells more effectively than IFNα2 alone and showed an elevated genotoxic effect. The expression of proapoptotic genes was also significantly enhanced in IFNα2-Tα1-treated cells compared to IFNα2-treated cells. Furthermore, the HCV RNA level was significantly reduced in IFNα2-Tα1-treated HCV-infected Huh7 cells compared to IFNα2-treated cells. The quantitative PCR analysis showed that the expression of various genes, the products of which inhibit HCV replication, was significantly enhanced in IFNα2-Tα1-treated cells compared to IFNα2-treated cells. Our findings demonstrate that IFNα2-Tα1 is more effective than single IFNα2 as an anticancer and antiviral agent.

Mechanisms of the synergistic lung tumorigenic effect of arsenic and benzo(a)pyrene combined- exposure.

Humans are often exposed to mixtures of environmental pollutants especially environmental chemical carcinogens, representing a significant environmental health issue. However, our understanding on the carcinogenic effects and mechanisms of environmental carcinogen mixture exposures is limited and mostly relies on the findings from studying individual chemical carcinogens. Both arsenic and benzo(a)pyrene (BaP) are among the most common environmental carcinogens causing lung cancer and other types of cancer in humans. Millions of people are exposed to arsenic via consuming arsenic-contaminated drinking water and even more people are exposed to BaP via cigarette smoking and consuming BaP-contaminated food. Thus arsenic and BaP combined-exposure in humans is common. Previous epidemiology studies indicated that arsenic-exposed people who were cigarette smokers had significantly higher lung cancer risk than those who were non-smokers. Since BaP is one of the major carcinogens in cigarette smoke, it has been speculated that arsenic and BaP combined-exposure may play important roles in the increased lung cancer risk observed in arsenic-exposed cigarette smokers. In this review, we summarize important findings and inconsistencies about the co-carcinogenic effects and underlying mechanisms of arsenic and BaP combined-exposure and propose new areas for future studies. A clear understanding on the mechanism of co-carcinogenic effects of arsenic and BaP combined exposure may identify novel targets to more efficiently treat and prevent lung cancer resulting from arsenic and BaP combined-exposure.

Ecological risk assessment and long-term environmental pollution caused by obsolete undisposed organochlorine pesticides.

Obsolete organochlorine pesticides (OSPs) are currently prohibited as persistent organic pollutants that contaminate the environment. If undisposed, they continue to pollute soil and water, to accumulate in the food chain and to harm plants, animals and the human body. The aim of the study was to assess water and soil pollution around the storehouses of undisposed, banned OSPs and their possible genotoxic effect. The storehouses in four villages near Almaty, Kazakhstan were investigated. Chemical analysis confirmed contamination of water and soil around storehouses with OSPs. The genotoxic effect of water and soil samples was evaluated using model objects: S.typhymurium, D.melanogaster, sheep lymphocytes cultures and human lymphocytes cultures. It was found that water and soil samples caused mutagenic effect in all model systems. They increased the frequency of revertants in Salmonella, the frequency of lethal mutations in Drosophila chromosomes, and the frequency of chromosome aberrations in cultures of human and sheep lymphocytes. Although a genotoxic effect was demonstrated for each of these models, various models showed different sensitivity to the effects of pesticides and they varied degree of response. The association between the total content of OCPs in soil and the level of mutations for different model systems was discovered.

Genotoxic effect of exposure to polycyclic aromatic hydrocarbons (PAHs) in asphalt workers.

Asphalt workers are at risk due to exposure to asphalt fumes containing polycyclic aromatic hydrocarbons (PAHs). The main purpose of this study was to measure the urinary metabolite of PAHs and to determine its effect on micronucleus (MN) formation as an indicator of genotoxic damage. In this cross-sectional study, the MN frequency in 48 male asphalt workers exposed to PAHs was measured and compared with 48 male non-exposed employees. PAHs exposure was evaluated by determining urinary 1-Hydroxypyrene (1-OHP). The mean concentrations of 1-OHP in the exposed and non-exposed groups were 0.58 ± 0.41 µmol/mol creatinine and 0.38 ± 0.25 µmol/mol creatinine, respectively. 1-OHP concentration was significantly higher in smokers compared with non-smokers in both exposed and non-exposed groups. Moreover, the mean MN frequency in the exposed group was significantly higher than in the non-exposed group. The MN frequency was significantly higher in asphalt workers with a work history of ≥ 15 years compared to workers with lower work history. In a fully adjusted model, there was a statistically significant association between exposure to PAHs, with MN and 1-OHP concentration, and between smoking status with 1-OHP. The findings of the present study indicated that occupational exposure to PAHs was associated with increased urinary 1-OHP as well as DNA damage in the asphalt workers.

Biochemical, Histopathologic, and Genotoxic Effects of Ethanol Extract of Salvia hypargeia (Fisch. & Mey.) on Incisional and Excisional Wounded Diabetic Rats.

Purpose: Nonhealing wounds are a serious problem of diabetic patients. Salvia species are traditionally used for the treatment of wounds. The aim of the study was to investigate the effects of ointment prepared with ethanol extract obtained from the aerial parts of Salvia hypargeia, an endemic plant from Turkey, on diabetic rat incisional and excisional skin wounds. Materials and Methods: Male Wistar albino rats (n: 60) were divided into five groups. Diabetes was induced and two concentrations (0.5% and 1%) of the extract were used for ointments and applied on wounds for 7 and 14 days. Fito cream was chosen as a reference drug. Results: In excisional wounds, healing ratios of 0.5% (63.4% and 99.3%) and 1% (65.5% and 99.9%) S. hypargeia groups were higher compared to control (35.9% and 75.1%), and in incisional wounds, healing ratios of 0.5% (78.1% and 98.5%) and 1% (84.4% and 99.4%) S. hypargeia groups were higher compared to control (30.5% and 72.9%) (p < .01). Hydroxyproline (0.31 ± 0.3 and 0.34 ± 0.2) levels were lower and GSH (10.7 ± 3.1 and 7.6 ± 0.9) levels were higher in 0.5% and 1% S. hypargeia groups on the 14th day (p < .01). Histopathological results revealed re-epithelialization and formation of granulation tissue in all S. hypargeia groups. Genotoxicologic results indicated, GDI, DCP values, and MN frequency of 0.5% and 1% S. hypargeia groups did not reach to significant levels both on the 7 and 14 days. Conclusions: S. hypargeia may have a potential for therapeutic use in treatment and management of diabetic wounds with a successful topical application.

Toxicological effects of Ag2O and Ag2CO3 doped TiO2 nanoparticles and pure TiO2 particles on zebrafish (Danio rerio).

In this study, the toxic effects of silver oxide and silver carbonate doped TiO2 nanoparticles (Ag2O-TiO2 NPs and Ag2CO3-TiO2NPs), TiO2 nanoparticles (TiO2 NPs), and bulk TiO2 on gene expression, lipid peroxidation, genotoxicity, and histological alterations in zebrafish (Danio rerio) was assessed. The physicochemical properties of the synthesized nanoparticles were evaluated by X-ray diffraction (XRD), Scanning Electron Microscope (SEM), diffuse reflectance spectroscopy (DRS), dynamic light scattering (DLS), and Zeta potential analyses. TiO2NPs after doping with Ag showed shift to higher wavelengths and decrease of band gap energy. Also, remarkable reduction in the size of Ag-doped TiO2NPs in comparison with the TiO2 NPs was observed. According to our results, acute toxicity increased in the order of bulk TiO2 < TiO2 NPs < Ag2O-TiO2NPs < Ag2CO3-TiO2NPs, respectively. Results of sub-lethal experiments after 30 days of exposure, showed higher expression of Gpx, Hsp70, Ucp-2, and Bax genes, and lower expression of Bcl-2 gene in Ag-doped TiO2NPs than pure TiO2 particles (TiO2 NPs and bulk TiO2) treatments (p < 0.05). However, the mRNA levels of SOD and CAT genes were significantly higher in pure TiO2 particles than doped TiO2NPs (p < 0.05). Moreover, levels of malondialdehyde, abnormalities of peripheral blood cells and severity of histological lesions in liver, gill, intestine and kidney tissues were more evident in Ag-dopedTiO2 NPs than pure TiO2 particles. It can be concluded that Ag doping of TiO2 NPs significantly increased their toxicity and resulted in more histological lesions, apoptosis and oxidative stress than pure TiO2 particles in adult zebrafish.

Human Fibroblasts In Vitro Exposed to 2.45 GHz Continuous and Pulsed Wave Signals: Evaluation of Biological Effects with a Multimethodological Approach.

The increasing exposure to radiofrequency electromagnetic fields (RF-EMF), especially from wireless communication devices, raises questions about their possible adverse health effects. So far, several in vitro studies evaluating RF-EMF genotoxic and cytotoxic non-thermal effects have reported contradictory results that could be mainly due to inadequate experimental design and lack of well-characterized exposure systems and conditions. Moreover, a topic poorly investigated is related to signal modulation induced by electromagnetic fields. The aim of this study was to perform an analysis of the potential non-thermal biological effects induced by 2.45 GHz exposures through a characterized exposure system and a multimethodological approach. Human fibroblasts were exposed to continuous (CW) and pulsed (PW) signals for 2 h in a wire patch cell-based exposure system at the specific absorption rate (SAR) of 0.7 W/kg. The evaluation of the potential biological effects was carried out through a multimethodological approach, including classical biological markers (genotoxic, cell cycle, and ultrastructural) and the evaluation of gene expression profile through the powerful high-throughput next generation sequencing (NGS) RNA sequencing (RNA-seq) approach. Our results suggest that 2.45 GHz radiofrequency fields did not induce significant biological effects at a cellular or molecular level for the evaluated exposure parameters and conditions.

Chemical Composition, Antioxidant, Genotoxique and Antigenotoxic Potentials of Phlomis Bovei De Noé Aerial Parts.

In the present work, chemical investigation of the aerial parts of Phlomis bovei de Noé an endemic species from Algeria, led to the isolation and identification of seven known compounds including five flavones glycosides: Chrysoeriol 7-O-(3''-(E et Z)-p-coumaroyl)-ß-glucoside (1), terniflorin (apigenin-7-O-(6''-E-p-coumaroyl)glucoside) (3), apigenin-7-O-(6''-(5'''-methoxy-coumaryl) glucoside (4), apigenin 7-O-(3″-p-coumaryl)glucoside (5), hispidulin-7-O-glucuronide (6) and two cinnamic acid derivatives: p-coumaric acid methyl ester (E et Z) (2), chlorogenic acid (7). Compound 4 is described for the first time in the species bovei de Noé, the genus Phlomis and the Lamiaceae family. Structures elucidation was performed by comprehensive 1D and 2D NMR analyses, mass spectrometry and by comparison with literature data. Some pure compounds and extracts have been evaluated for their antioxidant activities through different methods: DPPH and ABTS assays as well as CUPRAC assay. Genotoxic and antigenotoxic activities of pure compounds were also evaluated in-vitro on Escherichia coli PQ37 cells by the SOS Chromotest.

Protective effect of the medicinal herb infusion "horchata" against oxidative damage in cigarette smokers: An ex vivo study.

Cigarette smoking has been associated with an increase in oxidative stress (OS) and is considered a predisposing factor to chronic noncommunicable diseases, whilst dietary antioxidants has been proposed as an alternative to cope with this oxidative stress. In this study, 20 smokers and 20 non-smokers were studied with the aim of determining their antioxidant status, as well as the ability of an infusion of 23 medicinal plants, to counteract the damage caused by OS. The plasma, red blood cells (RBCs) and polymorphonuclear cells (PBMCs) of both groups were incubated or not with the horchata infusion extract and then the OS markers, genotoxicity, nanostructure of RBCs membrane and genes related to oxidative responses and cellular functionality were evaluated. Up to 33 different compounds, mainly quercetin glycosides, were identified in the extract. A significant deterioration in the antioxidant status in smokers compared to non-smokers was found. The horchata infusion extract improved the nanostructure of RBCs and DNA damage, as well as the activity of the endogenous antioxidant enzymes and markers of oxidative damage to lipid, and proteins in plasma, RBCs and PBMCs in both groups, whilst no significant changes were found in the expression of different genes related to OS response.

Dalayed Effects of Antitumor Drug Paclitaxel on the Hereditary Material and Hemopoietic System of CBA Mice.

Paclitaxel in a single MTD of 40 mg/kg caused chromosome aberrations and genome changes (polyploidy) in the bone marrow cells of mice early and 3 months after the injection. The quantity of early precursors of erythropoiesis in the bone marrow decreased, as did their proliferative potential irrespective of the animal gender. Injection of paclitaxel in the MTD caused the development of bone marrow hypoplasia during the early period of observation (up to 14 days) and 3 months after injection.

Selective Cytotoxic Activity of Prodigiosin@halloysite Nanoformulation.

Prodigiosin, a bioactive secondary metabolite produced by Serratia marcescens, is an effective proapoptotic agent against various cancer cell lines, with little or no toxicity toward normal cells. The hydrophobicity of prodigiosin limits its use for medical and biotechnological applications, these limitations, however, can be overcome by using nanoscale drug carriers, resulting in promising formulations for target delivery systems with great potential for anticancer therapy. Here we report on prodigiosin-loaded halloysite-based nanoformulation and its effects on viability of malignant and non-malignant cells. We have found that prodigiosin-loaded halloysite nanotubes inhibit human epithelial colorectal adenocarcinoma (Caco-2) and human colon carcinoma (HCT116) cells proliferative activity. After treatment of Caco-2 cells with prodigiosin-loaded halloysite nanotubes, we have observed a disorganization of the F-actin structure. Comparison of this effects on malignant (Caco-2, HCT116) and non-malignant (MSC, HSF) cells suggests the selective cytotoxic and genotoxic activity of prodigiosin-HNTs nanoformulation.