Blood Micronucleus Research Articles

Mechanistic insights into acetamiprid-induced genotoxicity on the myocardium and potential ameliorative role of resveratrol

The current study aimed to explore the genotoxic impacts of the insecticide acetamiprid (ACP) on the myocardium and assess the ameliorative role of resveratrol (RSV). Male rats (10/group) were treated via oral route for 90 days: control; ACP (25 mg/kg); RSV (20 mg/kg); ACP+RSV. Peripheral blood micronucleus test, oxidative stress analysis, comet assay, 8-hydroxydeoxyguanosine and gene expression assessment were performed. The findings revealed that ACP has myocardial genotoxic effects, as demonstrated by increased micronucleus and 8-hydroxydeoxyguanosine formation and increased all comet parameters. Oxidative stress analysis demonstrated that ACP elevated H2O2 and NO levels while decreasing catalase and GST activities. Acetamiprid dysregulated the expression of genes related to oxidative stress and DNA damage response. However, RSV co-treatment resulted in significant protection against these genotoxic impacts. Resveratrol reduced DNA damage and restored the oxidative balance in the myocardium. Moreover, RSV modulated the Nrf2/HO-1 and Atm/P53 pathways, potentiating antioxidant defense and DNA repair.

Comparison of sensitivity between blood parameters and a genotoxic biomarker at low blood Pb levels: A population-based study

BackgroundPrevious studies reported that lead (Pb) exposure induced adverse health effects at high exposure concentrations, however, there have been limited data on sensitivity comparisons among different health outcomes at low blood Pb levels. ObjectivesTo compare sensitivity between blood parameters and a genotoxic biomarker among workers exposed to low blood Pb levels (< 20 µg/dl), and to estimate a benchmark dose (BMD). MethodsPb-exposed workers were recruited from a lead-acid storage battery plant. Their blood lead levels (BLLs) were measured. Blood parameters and micronuclei (MN) frequencies were determined. Multivariate linear or Poisson regression was used to analyze relationships between blood parameters or MN frequencies with BLLs. Two BMD software were used to calculate BMD and its 95 % lower confidence limit (BMDL) for BLLs. ResultsThe median BLL for 611 workers was 10.44 µg/dl with the 25th and 75th percentile being 7.37 and 14.62 µg/dl among all participants. There were significantly negative correlations between blood parameters and BLLs. However, MN frequencies correlated positively with BLLs (all P<0.05). Results from the two BMD software revealed that the dichotomous model was superior to the continuous model, and the BMDL for BLL derived from red blood cell (RBC) was 15.11 µg/dl, from hemoglobin (HGB) was 8.50 µg/dl, from mean corpuscular hemoglobin (MCH) was 7.87 µg/dl, from mean corpuscular hemoglobin concentration (MCHC) was 3.98 µg/dl, from mean corpuscular volume (MCV) was 11.44 µg/dl, and from hematocrit (HCT) was 6.65 µg/dl. The conservative BMDL obtained from the MN data was 7.52 µg/dl. ConclusionOur study shows that low dose Pb exposure caused decrease of blood parameters and increase of MN frequencies. The genotoxic biomarker was more sensitive than most blood parameters. BMDLs for BLL derived from MN frequencies and the red blood cell indicators should be considered as new occupational exposure limits. Our results suggest that MN assay can be considered as a part of occupational health examination items.

Evaluation of the Antigenotoxic Potential of Two Types of Chayote (Sechium edule) Juices.

Sechium edule (Jacq.) Swartz is a perennial herbaceous climbing plant with tendrils and tuberous roots belonging to the Cucurbitaceae family. Its fruits ("chayote"), stems, roots, and leaves are edible and are commonly ingested by humans. It has shown medicinal properties attributed to its bioactive compounds (vitamins, phenolic acids, flavonoids, carotenoids, triterpenoids, polyphenolic compounds, phytosterols, and cucurbitacins), which together have been associated with the control and prevention of chronic and infectious diseases, highlighting its antibacterial, anti-cardiovascular/antihypertensive, antiepileptic, anti-inflammatory, hepatoprotective, antiproliferative, and antioxidant activities. The objective of the study was to determine the antigenotoxic potential of two types of fresh chayote juice (filtered (FChJ) and unfiltered (UFChJ)) against DNA damage produced by benzo[a]pyrene (B[a]P) using an in vivo mouse peripheral blood micronucleus assay (MN). The juices were consumed freely for 2 weeks. A negative control, a control group of each juice, a positive batch [B[a]P], and two combined batches (B[a]P plus FChJ or UFChJ) were included. Blood smears were stained and observed under a microscope to quantify the number of micronucleated normochromic erythrocytes (MNNEs). The results indicate: (a) B[a]P increased the frequency of MNNEs and reduced the rate of PEs; and (b) no juice produced toxic effects or induced MN. On the contrary, both juices were genoprotective. However, the most significant effect was presented by UFChJ at the end of the experiment (70%). It is suggested that UFChJ has a greater amount of fiber and/or phytochemicals that favor the therapeutic effect. Possibly, the genoprotection is also related to its antioxidant capacity.

Immune Regulation Patterns in Response to Environmental Pollutant Chromate Exposure-Related Genetic Damage: A Cross-Sectional Study Applying Machine Learning Methods.

Exposure to hexavalent chromium damages genetic materials like DNA and chromosomes, further elevating cancer risk, yet research rarely focuses on related immunological mechanisms, which play an important role in the occurrence and development of cancer. We investigated the association between blood chromium (Cr) levels and genetic damage biomarkers as well as the immune regulatory mechanism involved, such as costimulatory molecules, in 120 workers exposed to chromates. Higher blood Cr levels were linearly correlated with higher genetic damage, reflected by urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and blood micronucleus frequency (MNF). Exploratory factor analysis revealed that both positive and negative immune regulation patterns were positively associated with blood Cr. Specifically, higher levels of programmed cell death protein 1 (PD-1; mediated proportion: 4.12%), programmed cell death ligand 1 (PD-L1; 5.22%), lymphocyte activation gene 3 (LAG-3; 2.11%), and their constitutive positive immune regulation pattern (5.86%) indirectly positively influenced the relationship between blood Cr and urinary 8-OHdG. NOD-like receptor family pyrin domain containing 3 (NLRP3) positively affected the association between blood Cr levels and inflammatory immunity. This study, using machine learning, investigated immune regulation and its potential role in chromate-induced genetic damage, providing insights into complex relationships and emphasizing the need for further research.

Induction of micronuclei in blood and histopathological alterations in gill, kidney and liver of Channa punctatus (Bloch, 1793) exposed to copper sulphate

Copper is one of the most toxic metals to fish and causes cytotoxic, mutagenic and carcinogenic effects. The accumulation of copper in an aquatic environment directly impacts man and the aquatic ecosystem. The present study aimed to determine the effect of copper sulphate (CuSO4) accumulation on the induction of micronuclei in blood and histological changes in kidney and liver of the fish Channa punctatus. The test chemical LC50 was determined after 96 hours during the first experiment. Later in the second experiment, the test animal was exposed to three sub-lethal concentrations of CuSO4 [0.1 mg/l (96 h-LC50/40), 0.2 mg/l (96 h-LC50/20) and 0.4 mg/l (96 h-LC50/10)]. Physico chemical parameters of the test medium, such as pH, temperature, hardness, alkalinity, and dissolved oxygen, were observed throughout the experiment, and all values were within the ranges necessary for the fish's survival. At intervals of 7, 14, 21, and 28 days, the control (without any test chemical) and copper sulphate exposed Groups' blood, liver, kidney, and gill tissues were taken to evaluate changes in genotoxic and histological parameters. Micronuclei (MN) induction and nuclear abnormalities (NAs) were observed at regular intervals. After 28 days, the MN frequency in Groups 1, 2, 3, and 4 was 0.78±0.006, 8.40±0.052, 10.37±0.098 and 10.90±0.024 respectively. A significant (P&lt; 0.05) rise in MN frequencies and NAs indicated fish erythrocytes' DNA damage. Histological analysis of the liver, kidney, and gills revealed serious tissue injury such as necrosis, vacuolization, and degeneration after 28 days in the exposed Groups. The present study observed changes due to genotoxicity and histology, giving the most comprehensive understanding of CuSO4 stress on the fish C. punctatus and its risks to human health.

Correlation analysis of urinary arsenic species and health effect indicators of occupational arsenic exposure workers

Objective: To explore the correlation between urinary arsenic and health effects through the determination and analysis of urinary arsenic levels in occupational arsenic exposed workers. Methods: In November 2021, 95 workers exposed to arsenic and its inorganic compounds and 31 administrative personnel from a non-ferrous metal smelter in Yunnan Province were selected as the contact group and control group, respectively. Urine forms of arsenic, blood tumor markers, liver function were detected, and micronucleus test was used to analyze the chromosome damage. The correlation between urine forms of arsenic and health effects were analyzed. Results: Compared with the control group, the concentrations of urinary trivalent inorganic arsenic (iAs(3+)) , pentavalent inorganic arsenic (iAs(5+)) , inorganic arsenic (iAs=ΣiAs(3+)+iAs(5+)) , monomethyl arsenic (MMA) , dimethyl arsenic (DMA) and urinary arsenic (ΣiAs+MMA+DMA) at the end of class in contact group were higher (P<0.05) . There was no statistically significant difference in blood tumor markers and liver function indicators between the two groups (P>0.05) . Compared with the control group, the peripheral blood micronucleus rate and cell micronucleus rate in the contact group were significantly increased (P<0.05) . The urinary arsenic, iAs(5+), inorganic arsenic and DMA were positively correlated with peripheral blood micronucleus rate in contact group (r(s)=0.48, 0.34, 0.37, 0.23, P<0.05) , and the urinary arsenic, iAs(5+), DMA were positively correlated with peripheral blood micronucleus rate (r(s)=0.48, 0.34, 0.26, P<0.05) . Conclusion: There is a significant correlation between different valence states of arsenic in the urine and abnormal health effects of occupational arsenic exposed workers. It is necessary to strengthen the detection of arsenic species in the urine of occupational arsenic exposed workers to better protect their health.

N-Nitrosodimethylamine investigations in Muta™Mouse define point-of-departure values and demonstrate less-than-additive somatic mutant frequency accumulations.

The N-nitrosamine, N-nitrosodimethylamine (NDMA), is an environmental mutagen and rodent carcinogen. Small levels of NDMA have been identified as an impurity in some commonly used drugs, resulting in several product recalls. In this study, NDMA was evaluated in an OECD TG-488 compliant Muta™Mouse gene mutation assay (28-day oral dosing across seven daily doses of 0.02-4 mg/kg/day) using an integrated design that assessed mutation at the transgenic lacZ locus in various tissues and at the endogenous Pig-a gene-locus, along with micronucleus frequencies in peripheral blood. Liver pathology was determined together with NDMA exposure in blood and liver. The additivity of mutation induction was assessed by including two acute single-dose treatment groups (i.e. 5 and 10 mg/kg dose on Day 1), which represented the same total dose as two of the repeat dose treatment groups. NDMA did not induce statistically significant increases in mean lacZ mutant frequency (MF) in bone marrow, spleen, bladder, or stomach, nor in peripheral blood (Pig-a mutation or micronucleus induction) when tested up to 4 mg/kg/day. There were dose-dependent increases in mean lacZ MF in the liver, lung, and kidney following 28-day repeat dosing or in the liver and kidney after a single dose (10 mg/kg). No observed genotoxic effect levels (NOGEL) were determined for the positive repeat dose-response relationships. Mutagenicity did not exhibit simple additivity in the liver since there was a reduction in MF following NDMA repeat dosing compared with acute dosing for the same total dose. Benchmark dose modelling was used to estimate point of departure doses for NDMA mutagenicity in Muta™Mouse and rank order target organ tissue sensitivity (liver > kidney or lung). The BMD50 value for liver was 0.32 mg/kg/day following repeat dosing (confidence interval 0.21-0.46 mg/kg/day). In addition, liver toxicity was observed at doses of ≥ 1.1 mg/kg/day NDMA and correlated with systemic and target organ exposure. The integration of these results and their implications for risk assessment are discussed.

Evaluation of genome stability, haematological and productivity performance of young mink when using dried palm fat

The article presents of the results on estimation genome stability, haematological and productive indices of young heads standard short-haired black mink, bred for pelts, when using in a diet supplement of dry palm fat during the period winter hair of formation (October-November). The control group of mink received a general farm diet without the additive. The palm fat additive was added to the feed mixture of the experimental group in an average amount of 0.75 g per 100 g of the feed mixture per day. It was found out that the composition the minks of the leukoformulas studied was within the physiological norm. Since four months of age, the young mink had a stable neutrophilic blood profile. Determination of the erythrocytes frequency containing micronuclei in the peripheral blood of young mink allowed to evaluate the stability (instability) of the genome during the introduction of dry palm fat to the diet. It was found that elevated frequency of erythrocytes containing micronuclei in the blood of males at the age of 7 months above the level of 7.7±1.84‰ (ppm) is connected with changes of diet composition and correlates with increase of live weight gain at conservation of morphophysiological characters and directed for realization of youngsters productivity - increase of area and good quality of skins.

Toxicity Profile Study of Antihypertensive Drug Prazosin in Pregnant Wistar Rats

The purpose of this research is to investigate and assess the cytotoxicity and genotoxicity of Prazosin HCL in pregnant rats. Prazosin (PZ) was administered to the animals intraperitoneally (IP) at dosages of 5, 15, and 25 mg/kg/body weight for single dose (14-day) toxicity tests. The following parameters have been examined for evaluating genotoxicity: bone marrow micronucleus assay, peripheral blood micronucleus assay, DNA damage is measured using the metaphase chromosomal analysis, DNA damage is measured using the DNA fragmentation test, and cytotoxicity is measured using a histological analysis. The results obtained clearly demonstrate that PZ induced hazardous responses at the higher dose in the hepatocytes, as evidenced by DNA damage, and increased DNA fragmentation in pregnant rats. Observing that PZ significantly increased DNA strand breakage and structural chromosomal aberrations in bone marrow cell lines is also fascinating. As a result, it is thought to be genotoxic to bone marrow and mouse hepatocyte cells. The current study showed that Prazosin had significant genotoxic effects in pregnant rats at the matching hepatotoxic dose level.

Evaluation of cyto-genotoxicity biomarkers, changes in histology and antioxidant defense system of Oreochromis niloticus induced by the industrial effluents

Aquatic pollution mainly by industrial effluents has been a major concern since a few decades. The current study evaluated cyto-genotoxicity of industrial effluents on Oreochromis niloticus exposed to sublethal levels by hematotoxicity, blood biochemistry analysis, micronucleus assay, antioxidants and cerebral toxicity. The significant elevation in differential leukocytes of exposed fish was indicative of infections and compromised immune system. The acute and chronic industrial effluent exposure caused significant decline in aspartame transaminase (AST) and alanine transaminase (ALT) and renal function enzymes. Necrosis, hyperplastic growth, hypertrophy and toxicant accumulation exhibited cerebral toxicity potential of industrial toxicants. A significant decrease in antioxidants, GSH, SOD and catalase (0.14, 0.66 and 1549 unit/mg protein) in chronic exposure group in comparison to 0.18, 2.83, 7680 and 6200.8 values of GSH, SOD, GPx and CAT, respectively. Results showed that acute and chronic industrial effluent exposure caused genotoxicity with higher frequencies of formation of micronuclei and cytokaryotic fusion.

Effects of haloperidol on peripheral erythrocytes and brain neurotransmitter levels of juvenile African Sharptooth Catfish Clarias gariepinus.

The study investigated the effects of haloperidol on peripheral erythrocytes and brain neurotransmitter levels of juvenile African Sharptooth Catfish Clarias gariepinus. Juveniles were exposed to different concentrations of haloperidol (0.12, 0.24, and 0.48 mg/L) for 15 days and subsequently withdrawn from the drug for 5 days. Blood samples from the fish on days 1, 5, 10, and 15 and after the 5-day withdrawal period were analyzed for mutagenic changes, after which the fish were sacrificed. The brain was sampled for serotonergic and dopaminergic analyses. There was formation of micronuclei in the peripheral fish blood, which increased as the duration and concentrations of the drug increased. The drug significantly reduced the serotonin activity but increased dopamine activity. Some of the studied parameters, however, recovered from the effects of the drug after the 5-day withdrawal period. Haloperidol is toxic to fish, and its use in the environment should be guarded to avoid adverse impacts on nontarget species like fish.

Melphalan induced germ cell toxicity and dose-dependent effects of β-aminoisobutyric acid in experimental rat model: Role of oxidative stress, inflammation and apoptosis.

The success of chemotherapy regimens has led to an increase in cancer survival rate over the last decades. Melphalan has been widely used for the treatment of several types of cancers despite its gonadotoxic effects. Due to its ability to cause mutations in the spermatogonial stem cells and spermatids, melphalan can exert a negative impact on male reproductive health in young cancer survivors. β-aminoisobutyric acid (BAIBA), a myokine released by skeletal muscles, has been reported to have beneficial effects in diabetic nephropathy, cardiomyopathy and hepatic toxicity. However, the exact role of BAIBA in chemotherapy-induced germ cell toxicity is still unexplored. The present study aims to determine the dose-dependent (25, 50, and 100 mg/kg) effects of BAIBA on melphalan-induced (1.5 mg/kg) germ cell toxicity in sprague-dawley (SD) rats. The evaluation parameters included quantification of oxidative stress biomarkers, sperm count, sperm motility and head morphology, sperm and testicular DNA damage, sperm mitochondrial membrane potential, ultrastructural changes in sperms, histological and protein expression studies in testes. Melphalan treatment significantly altered all the above-mentioned parameters and the high dose (100 mg/kg) of BAIBA restored melphalan-induced toxicity in a significant manner by exerting antioxidant, anti-inflammatory and antiapoptotic effects. However, the medium dose (50 mg/kg) of BAIBA decreased the toxicity of melphalan and the low dose (25 mg/kg) of BAIBA failed to counteract the melphalan-induced male germ cell toxicity as well as the peripheral blood micronucleus induction. The antioxidant, anti-inflammatory and antiapoptotic role of BAIBA in melphalan-induced gonadal damage is a novel finding in an experimental rat model.

THE INFLUENCE OF THE KETONE DIET ON THE LEUKOCYTE FORMULA, STABILITY AND ACTIVITY OF THE GENETIC MATERIAL OF MICE

The effect of a 14-day ketogenic diet on the level of erythrocytes with micronuclei, the activity of nucleolar-forming regions in lymphocytes, and the leukocyte blood count of 8-week-old male C57BL/6 mice was studied. It was found that in animals receiving a ketone diet, the proportion of erythrocytes with Jolly bodies was 18.7 times higher than in mice in the control group receiving a standard diet. The diet did not cause changes in nucleolar activity in lymphocytic cells of the peripheral blood of experimental animals. A slight increase in the level of neutrophils in mice from the experimental group compared with the control was found, probably induced by a change in the biochemical composition of the blood (ketodiet mimics the state after fasting or heavy exercise, which may be accompanied by slight neutrophilia). A significant increase in the proportion of erythrocytes with micronuclei in the peripheral blood of animals of the experimental group may be due to a violation of cell maturation under conditions of severe deficiency of the main energy source for red blood cells — glucose and the inability to use ketone bodies as an energy substrate.

Rate of detection of erythrocytes with micronuclei in peripheral blood of rabbits in spontaneous coccidiosis

Coccidiosis is the most common disease in rabbits, causing great economic damage in rabbit farming. The aim of this work was to study the effect of coccidia on the parameters of the micronucleus test, since the authors did not come across data on the study of the mutagenic effect of Eimeria metabolites on the chromosomal apparatus of somatic cells in rabbits in the literature. For the experiment, 4 groups of rabbits, 10 heads each, with high, medium, low intensity of invasion (II) by oocysts of coccidia and healthy animals were formed. In experimental and control rabbits, blood was taken from the marginal ear vein, smears were prepared and stained with Giemsa dye. To carry out the micronucleus test, microscopy of blood preparations was performed and the frequency of occurrence of erythrocytes with micronuclei was calculated. It was found that in rabbits with low IS, the frequency of occurrence of erythrocytes with micronuclei was 1.49 + 0.10, which was 1.6 times higher than that of the control group (p &lt;0.001). In the group of rabbits with medium IS, the frequency of appearance of erythrocytes with micronuclei was 2.3 times higher than in the control group (p &lt;0.001) and was 2.15 + 0.09. The frequency of occurrence of erythrocytes with micronuclei in the group with high IS exceeded the control indicator by 3.1 times and amounted to 2.88 + 0.13 ‰. According to the results of laboratory studies, it was found that the change in the frequency of occurrence of erythrocytes with micronuclei in the peripheral blood of rabbits depends on the degree of invasion by eimeria, thereby proving the mutagenic effect of eimeria metabolites on the chromosomal apparatus of the host somatic cells.

Exposure in the tobacco fields: Genetic damage and oxidative stress in tobacco farmers occupationally exposed during harvest and grading seasons

Agricultural workers engaged in tobacco cultivation are constantly exposed to large amounts of harmful agents, such as pesticides and nicotine. Furthermore, most of the flue-cured tobacco leaves are manually graded exposing workers to agents such as tobacco-specific nitrosamines. This study aimed to evaluate genetic damage and oxidative stress in tobacco farmers occupationally exposed during the harvest and grading seasons. We obtained data on DNA damage detected in Comet assay in blood cells and micronucleus experiment with buccal cells from 241 individuals. The serum cotinine levels and nitrates were also evaluated. The Comet Assay results showed a showed an increased visual score for males and females during harvest time and tobacco grading. An increase of micronucleated and binucleated cells was observed in the grading group compared to the control and harvest groups. The oxidative stress measurements showed a clear increase of thiobarbituric acid reactive substances (TBARS) in tobacco farmers during harvest time, and trolox equivalent antioxidant capacity (TEAC) in individuals during harvest and grading time compared to the controls. Significant increases of the cotinine levels were observed during the harvest and grading period (harvest>grading), and nitrates for the grading period compared to the control. In this study, tobacco farmers presented compromised DNA integrity associated with enhanced oxidative stress levels.

Safety Assessment of Lactiplantibacillus plantarum TWK10 Based on Whole-Genome Sequencing, Phenotypic, and Oral Toxicity Analysis.

Lactiplantibacillus plantarum TWK10 (TWK10), isolated from Taiwanese pickled cabbage, has been demonstrated to exert beneficial probiotic effects in both mice and humans. Here, we comprehensively assessed the safety of TWK10 using both in vivo and in vitro approaches, including whole-genome sequence analysis, an assessment of hemolytic activity, and performing an antimicrobial susceptibility test, the Ames bacterial reverse mutation assay, the chromosomal aberration test, a rodent peripheral blood micronucleus test, and the 28-day subacute oral toxicity assay. The results showed that there was no significant increase in the incidence of reverse mutations or chromosomal aberrations following exposure to TWK10. Moreover, no significant changes were detected either in the number of reticulocytes or the incidence of micronuclei in ICR mice, and no subacute toxicity was recorded in SD rats at the oral TWK10 dosage of 2000 mg/kg body weight/day repeated for 28 days. Additionally, TWK10 exhibited no hemolytic activity and was susceptible to all the antibiotics tested, except kanamycin. However, no antimicrobial resistance genes, virulence factors, or genes involved in biogenic amine synthesis were found in the genome of TWK10. Our findings demonstrated that TWK10 has high potential of being safe for human consumption as a probiotic.

Toxicological and chemoprevention studies of Dalbergia ecastaphyllum (L.) Taub. stem, the botanical source of Brazilian red propolis.

Dalbergia ecastaphyllum (L.) Taub. is a semi-prostrate species associated with estuaries, mangroves and dunes. This plant species has great ecological and economic importance, especially concerning apiculture pasture and Brazilian red propolis production. In this study, non-clinical toxicological evaluations of the hydroalcoholic extract of D. ecastaphyllum stems (DEHE), the resin production source, were conducted. In addition, the action of DEHE on genomic instability and colon carcinogenesis was investigated. The extract's chemical profile was analysed by HPLC, and medicarpin, vestitol and neovestitol were found as major compounds. DEHE showed an IC50 equivalent to 373.2 µg/ml and LC50 equal 24.4mg/L, when evaluated using the XTT colorimetric test and the zebrafish acute toxicity assay, respectively. DEHE was neither genotoxic nor cytotoxic at the highest dose, 2000mg/kg, by peripheral blood micronucleus test. The treatments DEHE (6 and 24mg/kg) led to the reduction of micronuclei induced by doxorubicin (DXR) in mice. Furthermore, significantly higher serum levels of reduced glutathione were observed in animals treated with DEHE plus DXR, revealing an antioxidant effect. Treatments with DEHE (48mg/kg) led to a significant reduction in pre-neoplastic lesions induced by the 1,2-dimethylhydrazine (DMH) carcinogen in the rat colon. Immunohistochemical analysis revealed significantly lower levels of expression of COX-2 (86%) and PCNA (83%) in the colon of rats treated with DEHE plus DMH, concerning those treated with the carcinogen. These results indicate the involvement of anti-inflammatory and antiproliferative pathways in the protective effect of DEHE.

Potassium bromate-induced oxidative stress, genotoxicity and cytotoxicity in the blood and liver cells of mice

Potassium bromate (KBrO3) is an oxidising agent that is extensively used as a food additive, it is also a product of cosmetic and pharmaceutical relevance. The objective of this study was to evaluate the oxidative stress, genotoxicity, and apoptosis induced by KBrO3 in an experimental animal model. To study the toxic effects and oxidative stress, different doses of KBrO3 below LD50 (The half maximal lethal dose, 50, 100 and 150 mg/kg body weight) were given intraperitoneally to the mice for multiple time periods (24, 48, and 72 h). The results showed that KBrO3 significantly induces oxidative damage by increasing the levels of reactive oxygen species (ROS) and lipid peroxidase and depleted the levels of catalase (CAT), superoxide dismutase (SOD) and glutathione (GSH) enzymes in the serum and liver. Moreover, a significant increase of chromosomal aberrations in bone marrow cells and an elevated incidence of micronuclei in the peripheral blood of mice were observed. KBrO3 induces 3 ´ -OH end double-strand DNA breaks, which was evident in liver sections of the treated mice, and increases the percentage of apoptotic cells, as observed in TUNEL assays and flow cytometry analysis. The present findings indicate that KBrO3 induces oxidative stress, genotoxicity, and cytotoxicity in a dose- and time-dependent manner in mice.

Radioprotective effects of gallic acid on bone marrow cells in mice

To investigate the radioprotective effect of gallic acid(GA) on mouse bone marrow cells. Healthy male ICR mice were randomly divided into saline control group, GA control group, X-ray irradiation group and GA protection group, with 10 mice in each group. X-ray irradiation group and normal saline control group were given 0.01 mL/g normal saline gavage, GA control group and GA protection group were given 200 mg/kg GA(20 mg/mL) gavage once a day for 14 consecutive days. On the 15 th day, 4 X-ray irradiation groups and 4 GA protection groups were given one-time X-ray irradiation to the whole body of the mice, and the absorbed doses were 1.0, 2.0, 3.0 and 4.0 Gy, respectively. The saline control group and the GA control group were not irradiated. After irradiation, detected the whole blood catalase(CAT), superoxide dismutase(SOD), malondialdehyde(MDA) and micronucleus frequency of polychromatic erythrocyte in bone marrow(MN-PCE), and use flow cytometry to detect bone marrow cell cycle, early apoptosis rate and late apoptosis rate. The CAT activities in the serum of mice in the 1.0, 2.0, 3.0 and 4.0 Gy GA protection groups were 2.13, 1.74, 1.49 and 1.15 U/mL, respectively, which were significantly increased compared with the corresponding X-ray irradiation group(P&lt;0.01). SOD activities were 184.69, 156.92, 139.17 and 107.15 U/mL, which were significantly increased compared with the corresponding X-ray irradiation group(P&lt;0.01). The contents of MDA were 3.92, 4.20, 6.32 and 9.31 nmol/mL, which were significantly lower than those of the corresponding X-ray irradiation group(P&lt;0.05, P&lt;0.01). The bone marrow MN-PCE rate of the mice in the 1.0, 2.0, 3.0 and 4.0 Gy GA protection groups were 4.35‰, 8.00‰, 12.90‰ and 3.80‰, respectively, which were significantly lower than those in the corresponding X-ray irradiation group(P&lt;0.01). The proportions of G_0/G_1 phase cells of bone marrow cells in the 1.0, 2.0, 3.0 and 4.0 Gy GA protection group were 81.00%, 86.28%, 92.04% and 93.15%, respectively, which were significantly reduced compared with the corresponding X-ray irradiation group(P&lt;0.01). The proportions of G_2/M phase cells were 4.51%, 3.05%, 2.35% and 1.81%, which were significantly increased compared with the corresponding X-ray irradiation group(P&lt;0.05, P&lt;0.01). The proportions of S phase cells were 15.32%, 11.36%, 5.96% and 4.92%, which were significantly increased compared with the corresponding X-ray irradiation group(P&lt;0.01). The early apoptosis rate of bone marrow cells of mice in the 1.0, 2.0, 3.0 and 4.0 Gy GA protection groups were 3.32%, 8.96%, 12.11% and 2.26%, respectively, which were significantly reduced compared with the corresponding X-ray irradiation group(P&lt;0.01). The late apoptosis rates of bone marrow cells were 7.21%, 11.73%, 17.11% and 19.36%, which were significantly reduced compared with the corresponding X-ray irradiation group(P&lt;0.05, P&lt;0.01). GA can reduce the oxidative damage, DNA damage and bone marrow cell cycle arrest of the bone marrow cells of radiation-damaged mice, inhibit the apoptosis of bone marrow cells, and have radioprotective effects on the bone marrow cells of mice.

90-day nose-only inhalation toxicity study of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in Sprague-Dawley rats

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is one of the key tobacco-specific nitrosamines that plays an important role in human lung carcinogenesis. Repeated dose inhalation toxicity data on NNK, particularly relevant to cigarette smoking, however, is surprisingly limited. Hence, there is a lack of direct information available on the carcinogenic and potential non-carcinogenic effects of NNK via inhalational route exposure. In the present study, the subchronic inhalation toxicity of NNK was evaluated in Sprague Dawley rats. Both sexes (9–10 weeks age; 23 rats/sex/group) were exposed by nose-only inhalation to air, vehicle control (75% propylene glycol), or 0.2, 0.8, 3.2, or 7.8 mg/kg body weight (BW)/day of NNK (NNK aerosol concentrations: 0, 0, 0.0066, 0.026, 0.11, or 0.26 mg/L air) for 1 h/day for 90 consecutive days. Toxicity was evaluated by assessing body weights; food consumption; clinical pathology; histopathology; organ weights; blood, urine, and tissue levels of NNK, its major metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), and their glucuronides (reported as total NNK, tNNK, and total NNAL, tNNAL, respectively); tissue levels of the DNA adduct O6-methylguanine; blood and bone marrow micronucleus (MN) frequency; and bone marrow DNA strand breaks (comet assay). The results showed that NNK exposure caused multiple significant adverse effects, with the most sensitive endpoint being non-neoplastic lesions in the nose. Although the genotoxic biomarker O6-methylguanine was detected, genotoxicity from NNK exposure was negative in the MN and comet assays. The Lowest-Observed-Adverse-Effect-Level (LOAEL) was 0.8 mg/kg BW/day or 0.026 mg/L air of NNK for 1 h/day for both sexes. The No-Observed-Adverse-Effect-Level (NOAEL) was 0.2 mg/kg BW/day or 0.0066 mg/L air of NNK for 1 h/day for both sexes. The results of this study provide new information relevant to assessing the human exposure hazard of NNK.