Micronucleated Polychromatic Erythrocytes Research Articles

Evaluation of Low-Dose Effects and Non-Monotonous Dose Response of Butyl p-hydroxybenzoate, or Butylparaben on Female Wistar Rats

Butylparaben (BP) is an extensively used synthetic preservative that has been testified as an endocrine disruptor and speculated to be toxic for the body all together. The present study evaluated the possible noxious impact of BP at minimum doses, i.e., 1, 5, and 10 mg/kg BW/day, on female Wistar rats following consecutive subcutaneous exposure for 7 and 21 days. The results of the genotoxic study exhibited that BP at a dose of 10 mg/kg BW/day significantly (p ˂ 0.05) induced micronucleated polychromatic erythrocytes (MNPCEs) formation in bone marrow of rats, both in short (7.3 ± 0.87 MNPCEs/1000 PCEs) and long-term exposures (6.6 ± 0.33 MNPCEs/1000 PCEs), which was in line with the results obtained for 17β-estradiol (E2)-treated reference control rats. Levels of hepatic toxicity marker enzymes, i.e., aspartate transaminase (AST) and alanine transaminase (ALT), were not altered substantially in any of the study durations, but the alkaline phosphatase (ALP) level increased significantly (p ˂ 0.05) at all BP doses, including E2. Variations in the serum HDL as well as cholesterol levels were found to be non-monotonous with respect to the applied BP doses. However, contrasting specifics were observed for triglycerides in terms of the study durations. Conclusively, the current study established that BP, even at low doses, could evidently disturb the circulating lipid content, hepatic enzyme levels, and even cause genotoxicity, and also pointed toward its non-monotonous dose response.

Genotoxicity of Formaldehyde: Effect of Whole-Body Exposure on Polychromatic Erythrocyte/Normochromatic Erythrocyte Ratio in Male and Female Rats.

Every day, millions of individuals are exposed to formaldehyde (FA) due to its extensive presence and versatile use. Many in vivoand in vitroexperiments revealed that the mechanism of genotoxicity induced by FA exposure is complex yet toxicity upon whole-body exposure (WBE) to FA is less. As teachers, students, and skilled assistants in the health care sectors are also extensively exposed to FA vapors, it might result in genotoxicity. However, the effects of subchronic exposure to FA at low concentrations are not clear. Hence, analysis of the micronucleus (MN) was necessary to study the genetic toxicity triggered by FA in the bone marrow of male and female experimental rats. The present study is a gender- and duration of exposure-based assessment of the geno- and cytotoxicity in bone marrow cells of Wistar rats to study the effect of WBE to 10% FA on polychromatic erythrocytes/normochromatic erythrocytes (PCE/NCE) ratio and micronucleated polychromatic erythrocytes (MnPCE) in experimental rats. The obtained result clearly showed that WBE to FA for 60 days at concentrations between 1 and 1.1 ppm (0, 1, and 1.5 h) induced genotoxic effects in both male and female rats by altering the MnPCE% and significantly increasing the ratio of PCE/NCE (1.07 ± 0.23, 1.20 ± 0.20, 1.22 ± 0.14). The PCE/NCE ratio in male rats was lesser (0.98, 1.12, and 1.18) when compared with female rats (1.17, 1.29, and 1.26) with 0, 1, and 1.5 h exposure, respectively. Thus, the genetic/cellular sensitivity to FA differs among the sexes and also depends on the exposure duration.

Exposure assessment and micronuclei induction in populations exposed to electronic waste in South-West Nigeria

BACKGROUNDInformal electronic waste (e-waste) reprocessing in Nigeria is reportedly substantial in Africa, putting the growing exposed population at high risk of metal toxicity. This study aimed to investigate the existence of chromosomal aberration in the growing e-waste exposed populations in Nigeria, using induction of micronuclei (MN) expression in peripheral blood as an indicator. METHODSIn this cross-sectional study, 632 consenting participants were recruited from South-West Nigeria, consisting of 381 e-waste workers (EWW), 120 environmental e-waste exposed participants (EEP) and 131 age-matched unexposed participants (UP) serving as controls. A validated structured questionnaire was used to assess exposure pattern while frequency of micronucleated polychromatic erythrocytes (MNPCE)/1000PCE in peripheral blood film was determined by modified micronucleus assay. RESULTSA duration of exposure of ³5 years and exposure frequency ³6 hours/day; 6 days/week (9360 hours in any 5-year duration) was observed in both EWW and EEP. Routes of exposure observed in EWW entailed eyes, oral cavity, nasal cavity and skin. EWW that used personal protective equipment (PPE) while working was barely 10.24% while non-PPE users constituted the majority (89.76%) of the studied population. Frequency of MNPCE)/1000PCE in EWW (22.70 ± 0.15) was significantly higher than in EEP (4.17 ± 0.28), which in turn was significantly higher than the lowest frequency (0.99 ± 0.76) observed in UP (p<0.001). CONCLUSIONThe observed exposure pattern and the comparatively higher MN induction in the e-waste populations may suggest risk of significant cytogenetic damage and aberrant chromosomal changes associated with occupational e-waste reprocessing in Nigeria.

Genotoxic and cytotoxic evaluation of venlafaxine in an acute and a subchronic assay in mouse.

The present research was made to determine the micronuclei and cytotoxic capacity of the antidepressant venlafaxine in an in vivo acute and subchronic assays in mouse. In the first study, we administered once 5, 50, and 250 mg/kg of the drug, and included a negative and a daunorubicin treated group. Observations were daily made during four days. The subchronic assay lasted 5 weeks with daily administration of venlafaxine (1, 5, and 10 mg/kg) plus a negative and an imipramine administered groups. Observations were made each week. In the first assay results showed no micronucleated polychromatic erythrocytes (MNPE) increase, except with the high dose at 72 h. The strongest cytotoxic effect was found with 250 mg/kg at 72 h (a 51% cytotoxic effect in comparison with the mean control level). In the subchronic assay no MNPE increase was found; however, with the highest dose a significant increase of micronucleated normochromatic erythrocytes was observed in the last three weeks (a mean of 51% respect to the mean control value). A cytotoxic effect with the two high doses in the last two weeks was observed (a polychromatic erythrocyte mean decrease of 52% respect to the mean control value). Results suggest caution with venlafaxine.

Micronuclei in embryos of eight seabird species in northwestern Mexico: A biomarker of exposure to coastal pollution?

The micronucleus (MN) test may be used to evaluate genome instability in birds and the potential of different species to function as biomarkers of genotoxicity. However, little is known regarding genome instability in seabird embryos or the instability present among embryonic development stages. Therefore, the present study aimed to describe the frequencies of micronucleated erythrocytes (MNE) and micronucleated polychromatic erythrocytes (MNPCE) in blood samples collected from the embryos of eight seabird species nesting on the coast of Sinaloa, Mexico. An additional description of blood cell maturation along with embryo development during incubation was conducted based on the proportion of polychromatic erythrocytes (PCE), and the potential relationships between metals (Hg and Cd concentrations in egg content) and the MN frequencies in embryo blood were evaluated. The PCE proportion appears to decline as incubation advances (initial stage > intermediate stage > advanced stage), and the values varied between species (Suliformes/Pelecaniformes < Charadriiformes: Laridae), which may be related to differences among incubation periods and reproductive strategies. Interspecific variation in the MNPCE frequency was found in embryos showing advanced development, which could be related to both variations in life-history traits and ecological factors and not Hg or Cd exposure. The genomic instability values in this study are the first to be reported for embryos of seabird species nesting in a subtropical coastal region.

Withaferin A, a steroidal lactone, selectively protects normal lymphocytes against ionizing radiation induced apoptosis and genotoxicity via activation of ERK/Nrf-2/HO-1 axis

Increasing use of ionizing radiation (IR) in medicine, industry, agriculture and research ensues potential health hazards if not used properly or contained effectively. However, radioprotectors which are effective in clinical and/or accidental radiation exposures are still elusive. In this direction, we have explored the radioprotective potential of Withaferin A, a plant withanolide, which was recently shown to be safe and well tolerated in cancer patients in a clinical trial and is also known to be a radio-sensitizer in cancer cells. Our results show that, Withaferin A (WA) protected only normal lymphocytes, but not cancer cells, against IR-induced apoptosis and offered radioprotection even when added post-radiation exposure. WA treatment led to significant inhibition of IR-induced caspase-3 activation and decreased IR-induced DNA damage to lymphocytes and bone-marrow cells. WA reduced intracellular ROS and GSH levels and only thiol based anti-oxidants could abrogate the radio-protective effects of WA, indicating a crucial role of cellular/protein thiols in its biological activity. The inability of WA-glutathione adduct to offer radioprotection further underscored the role of cellular thiols. WA induced pro-survival transcription factor, Nrf-2, and expression of cytoprotective genes HO-1, catalase, SOD, peroxiredoxin-2 via ERK. Further, WA administration could rescue mice against radiation induced mortality, DNA damage, increase in micro-nucleated polychromatic erythrocytes (mn-PCEs) and increased ratio of polychromatic erythrocytes (PCEs) to Normochromatic Erythrocytes (NCEs) in bone-marrow, demonstrating its potent in vivo the radio-protective efficacy. In conclusion, WA selectively protects normal cells against IR-induced apoptosis via activation of cytoprotective Nrf-2 pathway.

Micronuclei analysis in mice peripheral blood exposed to polarized polychromatic noncoherent light (Bioptron® Light)

The increase in cancer in recent years suggests an inadvertent exposure to agents that cause genetic damage. The polarized polychromatic noncoherent light Bioptron® lamp is used to accelerate healing, among other therapeutic applications and its potential carcinogenic effects as a mitogenic agent have not been explored. The objective was to evaluate the genotoxicity of the Bioptron light therapy by means of the micronucleus assay in mouse erythrocytes. Male SKH1 hairless mice were randomly divided into six groups (5 mice/group); Group 1: negative control received ambient light; Group 2: positive control was exposed to ultraviolet light lamp A (UV-A) for 80 min; Experimental Groups 3–6 were exposed to the Bioptron lamp light for 10, 20, 40 and 80 min, respectively. Exposures in all groups were once a day for 4 days and blood smears were performed daily for 5 days and subsequently read with a microscope equipped with epifluorescence. The values of micronucleated erythrocytes (MNE), micronucleated polychromatic erythrocytes (MNPCE) and the proportion of polychromatic erythrocytes (PCE) were determined. The study group that received the UV-A light was the only one that increased MNE and MNPCE values, while in the groups exposed to the Bioptron lamp and the negative control did not show increases in any of the sampling days. In conclusion, under the conditions presented here, our results suggest that the light of the Bioptron lamp does not cause damage to the genetic material of SKH1 mice, by means of the micronucleus test in peripheral blood.

Ratlarda Nikel Sülfatın Genotoksisitesine Karşı Likopenin Koruyucu Etkisi

Aim: Nickel, which has a wide usage area in industries, has teratogenic, carcinogenic, immunotoxic, and genotoxic effects. In this study, the protective effects of lycopene, which has antioxidant properties, were investigated against genotoxicity caused by nickel sulfate. Materials and Methods: In the study, a total of 24 rats (Wistar albino) were divided into four groups: Group I (control) daily by saline intraperitoneal (i.p.) and corn oil oral gavage (0.5 ml); Group II nickel sulfate (20 mg/kg, i.p.) was dissolved in physiological saline; Group III lycopene corn oil (0.5 ml) was suspended by oral gavage at 20 mg/kg doses; Group IV lycopene was suspended in corn oil (0.5 ml) and given by oral gavage at 20 mg/kg doses, 2 hours later, nickel sulfate (20 mg/kg, i.p.) was administered for 21 days. Micronucleated polychromatic erythrocytes (MNPCE) and polychromatic erythrocytes (PCE) were examined by bone marrow micronucleus test, which is one of the genotoxicity tests. Results: It was determined that the administration of lycopene for preventive purposes decreased the MNPCE levels significantly (p

Costus speciosus extract protects against the oxidative damage of zearalenone via modulation of inflammatory cytokines, Nrf2 and iNOS gene expression in rats

Zearalenone (ZEN) is a non-steroidal estrogenic mycotoxin that induces severe health disturbances in humans and animals. This study aimed to determine the bioactive compounds in Costus speciosus extract (CSE) using GC-MS and evaluate its protective capability against ZEN-induced oxidative damage, genotoxicity, and cytotoxicity in rats. Six groups of male Sprague Dawley rats were treated orally for 15 days including the control group, CSE-treated groups at low (200 mg/kg b. w) or high (400 mg/kg b. w) dose, ZEN-treated group (40 μg/kg b. w), and the groups treated with ZEN plus the low or the high dose of CSE. Blood and tissue samples were collected for different assays and pathological analyses. The results of GC-MS indicated the identification of 6 compounds and Azulene was the major. Animals that received ZEN showed severe disturbances in serum biochemical, cytokines, oxidative stress indicators, mRNA expression of iNOS, Nrf2, and inflammatory-related genes. ZEN also increased micronucleated polychromatic erythrocytes (MNPCEs) and comet tail formation in bone marrow cells along with the disturbances in the histological architecture of the liver and kidney. Co-administration of CSE plus ZEN could normalize the majority of the tested parameters and the histological picture at a dose as low as 200 mg/kg b. w. Therefore, CSE protects against ZEN toxicity via its antioxidant activity, modulation of iNOS, inflammatory-related genes, and the Nrf2 pathway and it could be used in the endemic regions.

Modulatory effect of Luteolin on potassium dichromate‐induced nephrotoxicity, cardiotoxicity and genotoxicity via Kim‐1/Nrf2 signaling pathways

Environmental and occupational exposure to chromium compounds has become a potential aetiologic agent for kidney disease through excessive generation of free radicals, induction of apoptosis and exaggerated inflammatory responses. These are some pathophysiologic mechanisms of potassium dichromate (K2Cr2O7) toxicity with attendant nephrotoxicity and cardiotoxicity. The cardioprotective and nephroprotective effects of Luteolin, a known potent antioxidant were evaluated in this study as described; Group A (normal saline), Groups B (30 mg/kg K2Cr2O7), Group C (Luteolin 100 mg/kg and K2Cr2O7 30 mg/kg), and Group D (Luteolin 200 mg/kg and K2Cr2O7 30 mg/kg), respectively.Markers of antioxidant defense system, oxidative stress, blood pressure and micronucleated polychromatic erythrocytes (MnPEs) were determined. Immunohistochemistry of Kidney Injury molecule (Kim‐1), nuclear factor erythroid 2‐related factor 2 (Nrf2), and cardiac troponin I (CTnI) were also determined.Our results showed that administration of K2Cr2O7increased systolic, diastolic and mean arterial blood pressures, markers of oxidative stress, the frequency of micronucleated polychromatic erythrocytes together with a significant reduction in serum nitric oxide bioavailability.Immunohistochemical staining revealed higher expression of renal Kim‐1 and cardiac troponin I in rats intoxicated with K2Cr2O7. However, lower expression of renal and cardiac Nrf2 were also observed in Luteolin co‐administered rats. Furthermore, co‐treatment with Luteolin restored blood pressure parameters, with concomitant reduction in oxidative stress indicators, augmented in vivo antioxidant status and improved serum NO levels. Lowered expressions of Kim‐1, CTnI and up‐regulation of both cardiac and renal Nrf2, and reduced frequency of micronucleated polychromatic. Taken together, this study demonstrates for the first time the antihypertensive, cardioprotective, nephroprotective and antigenotoxic effects of Luteolin against potassium dichromate induced‐toxicity through antioxidant and radical scavenging mechanisms.

Inhibitory effects of saeu-jeot extract on NLRP3 inflammasome activation and radiation-induced micronucleus formation.

PurposeSaeu‐jeot, or shrimp paste, is a traditional Korean high‐salt fermented seafood. This study elucidated the effects of saeu‐jeot extract (SJE) on NLRP3 inflammasome activation and radiation‐induced micronucleus formation.MethodWe treated lipopolysaccharide‐primed mouse bone marrow‐derived macrophages with the NLRP3 inflammasome activators ATP and nigericin. We also analyzed the acute effects of ionizing radiation on micronucleated polychromatic erythrocytes (MnPCEs) in whole‐body gamma‐irradiated male BALB/c and C57BL/6 mice after oral administration of SJE.ResultsSJE significantly inhibited NLRP3 inflammasome activation, reducing IL‐1β secretion in vitro. In addition, the frequency of MnPCEs was significantly lower in SJE‐treated mice.ConclusionsSJE has anti‐inflammatory effects and reduces radiation‐induced chromosome damage. Advance in knowledge: There are no reports concerning the effects of SJE on NLRP3 inflammasome activation or radioprotection. This experiment showed the radioprotective effects of saeu‐jeot.

Pistacia lentiscus L. fruits showed promising antimutagenic and antigenotoxic activity using both in-vitro and in-vivo test systems

ABSTRACT Pistacia lentiscus L. is one of the most popular medicinal plants attributed to its beneficial properties on human health. However, few toxicogenetic studies have been carried out. Therefore, the aim of this study was to examine the potential genotoxic/antigenotoxic and mutagenic/antimutagenic properties of oil, ethyl acetate and ethanolic extracts of P. lentiscus L. fruits using in vitro the Ames and Umu assays, as well as in vivo micronucleus (MN) test. Extracts did not exert any significant mutagenic/genotoxic effects but provided protection against standard mutagenic and genotoxic agents including 2 nitrofluorene (2-NF) at 2.5 and 5 µg/ml; sodium azide at 5 and 10 µg/ml; 3-methylcholanthrene (3-MC) at 25 and 50 μg/ml; cyclophosphamide (CP) at 50 and 100 μg/ml; 4-nitroquinoline 1-oxide (4-NQO) at 0.05 µg/ml and 2-amino-anthracene (AA) at 0.2 µg/ml. Further, cytotoxicity and selectivity were examined on human hepatocarcinoma (HepG2), and MCF-7 breast cancer cell lines as well as a human normal-like fibroblast cell line (TelCOFS02MA) using MTT assay. Among all extracts, PF1 (ethanolic) showed the most significant selectivity index (SI) (HepG2:11.98; MCF7:4.83), which led to further investigations using an animal model. Oral administration of PF1 (125–1000 mg/kg b.w.) significantly decreased the number of micronucleated cells in CP -initiated (50 mg/kg b.w.) mice, while the number of micronucleated reticulocytes (MNRET), micronucleated polychromatic erythrocytes (MNPCE) or mitotic index (MI) were not markedly affected. Further, PF1 significantly enhanced catalase (CAT) and superoxide dismutase (SOD) activities in the livers and kidneys of these animals. The obtained results indicated the beneficial properties of P. lentiscus L. fruits for use in therapy against harmful effects of genotoxic and mutagenic agents. However, while promising it should be noted that the obtained results are preliminary and need to be confirmed prior to therapeutic use.

Mangifera indica L.: Assessing the cytogenotoxicity of aqueous extract through micronucleus and comet assays

Mangifera indica L., known as mango tree, is a species belonging to family Anacardiaceae, widely used in popular medicine whose leaves are used to treat several diseases. Although several studies did not detect the cytogenotoxic activity of M. indica leaf extract, other authors have observed these feature and highlighted the importance of further research about the toxic potential of M. indica leaf extract. The aim of the current research is to assess the cytogenotoxic potential of the aqueous extract of M. indica leaves through comet DNA assay and micronucleus test. It was possible observing significant increase in the number of micronucleated polychromatic erythrocytes (MNPCE) in mice subjected to the treatment with the extract, in addition to significant increase in DNA damage index in comparison to the negative control group. The extract also presented cytotoxic effect caused by significant reduction in the polychromatic:normochromatic erythrocyte (PCE/NCE) ratio in comparison to the negative control group. The extract of M. indica leaves is cytogenotoxic under the conditions used in the current research; this outcome highlighted the importance of comparative studies applied to the several used processing methods, as well as to cultivation conditions, to certify the safety in the popular use of medicinal plants.

Evaluation of Genotoxic and Cytotoxic Activity of Ganoderma Lucidum In Rat Bone Marrow Induced By Lipopolysaccharide

Objective: It was aimed to investigate the antigenotoxic effect of Ganoderma lucidum against the damage caused by lipopolysaccharide (LPS) in rat bone marrow cells by micronucleus test and comet analysis.&#x0D; Method: In the experiment, 28 Wistar albino female rats were used and 4 groups were formed. Only physiological saline was applied to the control group. A single dose of 7.5 mg/kg LPS was administered intraperitoneally to the LPS group. LPS+ Ganoderma lucidum (GL): Ganoderma lucidum was given by gavage at a dose of 50 mg/kg per day for one week. Then, on the 8th day, LPS was applied intraperitoneally. Ganoderma lucidum group: GL was given by gavage at 50 mg/kg per day for 1 week. After 24 hours, the rats were euthanized by cervical dislocation under anesthesia. Analyzes were performed for percentage of micronucleated polychromatic erythrocytes (MNPCE) and Polychromatic erythrocytes/Normochromatic erythrocytes (PCE/NCE) ratio and DNA damage in rat femur bone marrow cells.&#x0D; Results: When the percentage of micronucleus and PCE/NCE ratio were examined, no statistical significance was observed when the groups were compared both with the control and among themselves. Compared to the control group, it was observed that the comet parameters of the experimental groups (excluding the head DNA) increased significantly. Length tail (L tail), tail DNA, olive tail moment (OTM) values were significantly different both compared to the control and among themselves. While there was a significant difference between LPS+GL group and LPS and GL groups in Tail Moment (TM) value and Length comet (L comet) value, no difference was observed between LPS and GL groups.&#x0D; Conclusion: When all of the findings is considered, Ganoderma lucidum cannot be classified as a genotoxic agent. We can say, however, that it reverses the genotoxic damage in issue.

Radiation-induced effects on bone marrow of bank voles inhabiting the Chornobyl exclusion zone

Purpose To investigate the effects of chronic exposure to low-dose radiation on bone marrow hematopoiesis of bank voles inhabiting the radioactively contaminated territory of the Chornobyl exclusion zone. Materials and methods Animals were collected within the highly radioactive area of the so-called Red Forest located close to the destroyed 4th reactor of the Chornobyl Nuclear Power Plant. Radioecological investigations included evaluation of radiocontamination of soil samples by 90Sr and 137Cs, levels of incorporated radionuclides in animals’ bodies and organs, as well as the absorbed dose rates. The study of peripheral blood and bone marrow parameters combined with cytogenetic analysis of bone marrow micronucleated polychromatic erythrocytes and standard metaphase test was carried out. Results The blood system of the exposed animals manifested significant changes in peripheral blood parameters (anaemia and leucocyte formula left shift), ineffective differentiation and maturation of bone marrow cells, particularly relevant to the erythroid and granulocyte pools. Increased yields of bone marrow micronucleated polychromatic erythrocytes and chromosomal aberrations, including dicentrics and Robertsonian fusion-like configurations, were revealed. Conclusions Observed disturbances in the bone marrow and peripheral blood suggest functional instability and inefficient compensatory and recovery reactions of the blood system of the bank voles from the contaminated areas of the Chornobyl exclusion zone. We assume that they are the consequences both of direct radiation exposure and hereditary pathological changes that have formed in a number of generations inhabiting radioactively contaminated areas.

Improved antimutagenic effect of Pyrostegia venusta (Ker Gawl.) Miers nanostructured extract in liposome and polymeric nanoparticle

Pyrostegia venusta (Ker Gawl.) Miers, popularly known as “Cipó-de São-João”, has been used in traditional medicine for its therapeutic properties. Nanotechnology is able to enhance the pharmacological activity of plant extracts. In this context, liposomes and polymeric nanoparticles containing P. venusta ethanolic extract were developed and then physico-chemically characterized to evaluate the mutagenic/antimutagenic effects of P. venusta. In addition, transaminases and serum creatinine were biochemically analyzed for liver and renal damage, respectively. The micronucleus test was performed with male Swiss mice treated orally for 15 consecutive days with free extracts and nanostructured with P. venusta, and then intraperitoneally with N-ethyl-N-nitrosurea (50 mg/kg) on the 15th day of treatment. Micronucleated polychromatic erythrocytes (MNPCE) were evaluated in bone marrow. There was a significant reduction in the frequency of MNPCE (LPEPV = 183% and NPEPV = 114%, p < 0.001), indicating antimutagenic potential of the nanostructured extracts with P. venusta. The groups treated with only nanostructured extract did not show an increase in MNPCE frequency, and biochemical analyzes showed no significant difference between treatments. The liposomes and polymeric nanoparticles containing Pyrostegia venusta ethanolic extract showed biological potential in preventing the first step of carcinogenesis under the experimental conditions.

In vitro and in vivo evaluation of genotoxicity, cytotoxicity, and protective effects of synthetic chalcones (E)-3-(4-chlorophenyl)-1-phenyl-2-propen-1-one (4-CL) and (E)-3-(3,4-dimethoxyphenyl)-1- phenyl-2-propen-1-one (DMF)

The chalcones (E)-3-(4-chlorophenyl)-1-phenyl-2-propen-1-one (4-CL) and (E)-3-(3,4-dimethoxyphenyl)-1-phenyl-2 -propen-1-one (DMF) are versatile and easily synthesized into low-cost compounds that have a wide spectrum of biological activities. In this study, the cytotoxic, genotoxic and modulatory activities of 4-CL and DMF were evaluated using the Ames test and the mouse micronucleus assay. The results of the Ames test revealed that both chalcones did not show mutagenic activity in Salmonella typhimurium strains TA98 and TA100, and demonstrated significant antimutagenicity (p&lt; 0.05) when co-administered with sodium azide (SA) in strain TA100. In the micronucleus assay, both showed a significant increase in the frequency of micronucleated polychromatic erythrocytes (MNPCE) at 24 h and 48 h, revealing a genotoxic effect. In the co-treatment with mitomycin C (MMC) there was a significant decrease (p&lt; 0.05) in the frequency of MNPCE both in chalcones at 24h and in the less concentrated dose of DMF at 48h, demonstrating its antigenotoxic activity. 4-CL showed a significant decrease in the polychromatic/ normochromatic erythrocyte (PCE/ NCE) ratio at 24 and 48 h (p&lt; 0.05), indicating cytotoxicity. However, 4-CL and DMF when co-administered with MMC showed a significant increase in the PCE/NCE ratio within 24 hours, demonstrating anticytotoxicity. Furthermore, a biphasic dose-response behavior was observed in both chalcones, 4-CL in the co-administration with SA, in the Ames Test and DMF in the co-treatment with MMC, at 48 hours of exposure, in the micronucleus assay. In this study, 4-CL and DMF showed genotoxic, cytotoxic, antigenotoxic, anticytotoxic and no mutagenic properties.

Genotoxicity Assessment and Protective Effect of Anogeissus leiocarpus Roots against Cyclophosphamide-Induced DNA Damage In Vivo.

Background Belonging to the family of Combretaceae, the roots of Anogeissus leiocarpus are traditionally used to treat diabetes, wounds, infections, pain, and gastrointestinal diseases. To our knowledge, no genotoxicity assessment of the plant was reported. Hence, this study was designed to evaluate the potential genotoxic and protective effects of extract of Anogeissus leiocarpus roots using the micronucleus test on mice bone marrow cells in vivo. Methods Three different concentrations (250, 500, and 1000 mg·kg−1) of hydroalcoholic extract of roots of A. leiocarpus were administered daily for 7 days per os to mice, and the genotoxicity was induced by the administration ip of cyclophosphamide. Genotoxicity and cytotoxicity were evaluated by counting, respectively, the number of micronucleated polychromatic erythrocytes and polychromatic erythrocytes to total erythrocytes in the bone marrow of mice. Results The administration of A. leiocarpus did neither increase the ratio of the polychromatic erythrocyte (PCE) nor the frequency of micronucleated PCE (MNPCE) significantly in the bone marrow cells of the mice, compared to the vehicle control animals. However, a significant increase in the incidence of MNPCE in the bone marrow cell of the cyclophosphamide-treated mice was found. Moreover, in the groups treated with the total extract of A. leiocarpus at different doses plus cyclophosphamide, there was a significant decrease (p < 0.0001) in MNPCEs compared to the positive controls, in a dose-dependent manner. Conclusion This first finding reports that the extract of A. leiocarpus was neither genotoxic nor cytotoxic. However, it shows a protective effect against the genotoxicity and cytotoxicity induced by cyclophosphamide.

Cytotoxic and Genotoxic Evaluation of the Aqueous and Hydroalcoholic Leaf and Bark Extracts of Crataegus oxyacantha in Murine Model.

Crataegus oxyacantha has been mainly used in traditional medicine for the treatment of cardiovascular diseases. However, its safety profile has not been fully established, since only the genotoxic effects of C. oxyacantha fruit have been described. Therefore, the objective of this work was evaluating the cytotoxicity and genotoxicity of the aqueous and hydroalcoholic leaf and bark extracts of C. oxyacantha by means of the micronucleus test in a murine model. Doses of 2000, 1000, and 500 mg/kg of both extracts were administered orally for 5 days in mice of the Balb-C strain. Peripheral blood smears were performed at 0, 24, 48, 72, and 96 h after each administration. The number of polychromatic erythrocytes (PCEs), micronucleated polychromatic erythrocytes (MNPCEs), and micronucleated erythrocytes (MNEs) was determined at the different sampling times. Our results showed that the leaf and bark of C. oxyacantha increase the number of MNEs at the 2000 mg/kg dose, and only the aqueous leaf extract decreases the number of PCEs at the same dose. Therefore, the aqueous and hydroalcoholic leaf and bark extracts of C. oxyacantha showed genotoxic effects, and only the aqueous leaf extract exhibited cytotoxic effects.

Effect of N-acetylcysteine on attenuation of chlropyrifos and its methyl analogue toxicity in male rats

The attenuating effect of 150 mg/kg of N-acetylcysteine (NAC) against the oral administration of 7.88 and 202.07 mg/kg/day for 14 days of either chlropyrifos-ethyl (CPE-E) or chlropyrifos-methyl (CPF-M), respectively, in male rat was investigated using biochemical and genetic markers. Biomarkers such as acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), paraoxonase (PON), adenosine 5′-triphosphatase (ATP-ase), glutathione-S-transferase (GST), catalase (CAT), glutathione reduced (GSH) in serum showed a significant decline in their levels, while calcium (Ca+2), cytochrome C reduction (CYC-R), lipid peroxidation (LPO), nitric oxide (NO) levels showed a significant increase in serum of treated rats. Regarding the genotoxic parameters, when rats are treated either with CPE-E or CPF-M, liver DNA, chromosomal aberration (CA), and micronucleated polychromatic erythrocytes (MnPCE) significantly increased, while the mitotic index (MI) and polychromatic erythrocytes (PCE)/ normochromatic erythrocytes (NCE) ratio were significantly decreased. However, the administration of NAC following the intoxication of CPF-E or CPF-M attenuated the tested biochemical and genotoxic markers. It can be concluded that NAC can be used to ameliorate the toxicity of certain organophosphorus compounds such as CPF-E and CPF-M.