County-Level Atrazine Use and Gastroschisis.

Importance: The incidence of gastroschisis, a birth defect involving the herniation of the small bowel through the abdominal wall, has increased in the US since the 1960s. The pesticide atrazine is a hypothesized cause of gastroschisis; however, examination of the association between atrazine and gastroschisis has been limited. Objective: To evaluate national trends in gastroschisis incidence, maternal and infant characteristics associated with gastroschisis, and whether county-level atrazine use is associated with gastroschisis. Design, Setting, and Participants: This retrospective, repeated cross-sectional study examined birth certificate data of all live births in the US and data on atrazine use from the US Geological Survey from January 1, 2009, through December 31, 2019. The data analysis was performed between August 5, 2021, and May 26, 2023. Exposures: County-level atrazine use. Main Outcomes and Measures: The primary outcome was gastroschisis incidence. Covariates included maternal age, race and ethnicity, body mass index (measured by weight in kilograms divided by height in meters squared), parity, insurance type, Chlamydia infection during pregnancy, smoking, and rurality. Mixed-effects logistic regression models (year fixed effects and county random effects) were constructed using different county-level atrazine exposure variables (1-, 5-, and 10-year means). Results: Between 2009 and 2019, 39 282 566 live births were identified, with 10 527 infant diagnoses of gastroschisis. Infants with gastroschisis were more likely to have mothers who identified as non-Hispanic White (61% vs 54%; P < .001), had a lower body mass index (median [IQR], 23.4 [20.8-27.2] vs 25.4 [22.0-30.8]; P < .001), were more likely to be nulliparous (median [IQR], 0 [0-1] vs 1 [0-2]; P < .001), and were more commonly covered by Medicaid (63% vs 43%; P < .001). During the study period, the rate (per 1000 live births) of gastroschisis decreased from 0.31 (95% CI, 0.29-0.33) to 0.22 (95% CI, 0.21-0.24). The median (IQR) county-level atrazine use estimates were higher among infants with gastroschisis (1 year, 1389 [IQR, 198-10 162] vs 1023 [IQR, 167-6960] kg; 5 years, 1425 [IQR, 273-9895] vs 1057 [IQR, 199-6926] kg; 10 years, 1508 [IQR, 286-10 271] vs 1113 [IQR, 200-6650] kg; P < .001). In adjusted models, higher county levels of atrazine (each 100 000-kg increase) were associated with a higher incidence of gastroschisis (1 year: adjusted odds ratio [AOR], 1.12 [95% CI, 1.01-1.24]; 5 years: AOR, 1.15 [95% CI, 1.02-1.30]; 10 years: AOR, 1.21 [95% CI, 1.07-1.38]). Conclusions and Relevance: In this cross-sectional study, higher county levels of atrazine were associated with infant diagnoses of gastroschisis. While atrazine is the second-most used herbicide in the US, numerous countries around the world have banned it out of concern for adverse effects on human health. These findings suggest that exploring alternatives to atrazine in the US may be warranted.

Exposure to the herbicide atrazine induces oxidative imbalance, morphological damage and decreased survival in juvenile fish

Synthetic herbicides have been intensively used in weed control, although often involved in environmental contamination, critically affecting non-target species. However, never was investigated the effect of commercial formulation using atrazine on developing juvenile fish exposed for 35 days. Juveniles (Astyanax altiparanae) (n = 600) were assigned to the following ATZ-exposed groups: 0 (CTR-control), 0.56 (ATZ0.56), 1.00 (ATZ1.00), 1.66 (ATZ1.66) and 11.66 (ATZ11.66) µg/L. We found a 36.6% decrease in juvenile survival rate in the ATZ11.66 group compared to control and other groups. Juveniles from ATZ11.66 also showed hyperglycemia and increased cortisol levels. Increased the imbalance oxidative with an increase in malondialdehyde (MDA) and Carbonylated proteins levels markers in muscle, gills, and liver. We also found increased activity of the antioxidant enzymes superoxide dismutase (SOD) in gills and SOD and catalase (CAT) in muscles from ATZ11.66 fish, and increased glutathione S-transferase (GST) activities in the liver from all exposed groups compared to control. The morphological consequences of this were loss of secondary lamella integrity, increased mucus-secreting cells, hyperplasia, and lamellar fusion, as well as increased aneurysms percentage. The liver showed vascular congestion associated with endothelial hyperplasia, steatosis, and a decrease in the nuclei percentage. Our results showed that exposure to a commercial formulation of ATZ at 11.66 µg/L can be causing an imbalance in the oxidative markers and morphological damages and decreased survival in a juvenile Neotropical species of great ecological relevance and commercial interest.

Prolonged atrazine exposure beginning in utero and adult uterine morphology in mice.

Through drinking water, humans are commonly exposed to atrazine, a herbicide that acts as an endocrine and metabolic disruptor. It interferes with steroidogenesis, including promoting oestrogen production and altering cell metabolism. However, its precise impact on uterine development remains unknown. This study aimed to determine the effect of prolonged atrazine exposure on the uterus. Pregnant mice (n = 5/group) received 5 mg/kg body weight/day atrazine or DMSO in drinking water from gestational day 9.5 until weaning. Offspring continued to be exposed until 3 or 6 months of age (n = 5-9/group), when uteri were collected for morphological and molecular analyses and steroid quantification. Endometrial hyperplasia and leiomyoma were evident in the uteri of atrazine-exposed mice. Uterine oestrogen concentration, oestrogen receptor expression, and localisation were similar between groups, at both ages (P > 0.1). The expression and localisation of key epithelial-to-mesenchymal transition (EMT) genes and proteins, critical for tumourigenesis, remained unchanged between treatments, at both ages (P > 0.1). Hence, oestrogen-mediated changes to established EMT markers do not appear to underlie abnormal uterine morphology evident in atrazine exposure mice. This is the first report of abnormal uterine morphology following prolonged atrazine exposure starting in utero, it is likely that the abnormalities identified would negatively affect female fertility, although mechanisms remain unknown and require further study.

Atrazine Inhalation Worsen Pulmonary Fibrosis Regulating the Nuclear Factor-Erythroid 2-Related Factor (Nrf2) Pathways Inducing Brain Comorbidities.

BACKGROUND/AIMS: Pulmonary fibrosis can be caused by genetic abnormalities, autoimmune disorders or exposure to environmental pollutants. All these causes have in common the excessive production of oxidative stress species that initiate a cascade of molecular mechanism underlying fibrosis in a variety of organs, including lungs. The chemical name of Atrazine (ATR) is 6-chloro-N-ethyl-N'-(1-methylethyl)-1,3,5-triazine-2,4-diamine, and it is the most commonly used broad-spectrum herbicide in agricultural crops. Additionally, Bleomycin is a chemotherapeutic agent often used for different lymphoma with a seriously pulmonary complication. The most accredited hypothesis that may explain the mechanism of toxicity induced by ATR or bleomycin is exactly the production of reactive oxygen species (ROS) that leads to an unbalance in the physiological anti-oxidant system. However, until today, nobody has investigated the effect of ATR exposure during pulmonary fibrosis. METHODS: Mice were subject to ATR exposure, to bleomycin injection or to both. At the end of experiment, the lungs and blood were collected. Additionally, we analyzed by different test such as open field, pole and rotarod test or other we investigated the effects of ATR or bleomycin exposure on behavior. RESULTS: Following ATR or bleomycin induction, we found a significant increase in lung damage, fibrosis, and oxidative stress. This condition was significantly worsened when the animals injected with bleomycin were also exposed to ATR. Additionally, we observed significant motor and non-motor impairment in animals exposed to ATR. CONCLUSION: Our study demonstrates that ATR exposure, decrease nuclear factor-erythroid 2-related factor (Nrf2) pathways in both lung and brain.

Atrazine Inhalation Causes Neuroinflammation, Apoptosis and Accelerating Brain Aging.

BACKGROUND: exposure to environmental contaminants has been linked to an increased risk of neurological diseases and poor outcomes. Chemical name of Atrazine (ATR) is 6-chloro-N-ethyl-N'-(1-methylethyl)-1,3,5-triazine-2,4-diamine, and it is the most commonly used broad-spectrum herbicide in agricultural crops. Several studies have demonstrated that ATR has the potential to be harmful to the brain's neuronal circuits. Until today nobody has explored the effect of ATR inhalation on young and aged mice. METHODS: young and aged mice were subject to 25 mg of ATR in a vehicle made with saline and 10% of Dimethyl sulfoxide (DMSO) every day for 28 days. At the end of experiment different behavioral test were made and brain was collected. RESULTS: exposure to ATR induced the same response in terms of behavioral alterations and motor and memory impairment in mice but in aged group was more marked. Additionally, in both young and aged mice ATR inhalations induced oxidative stress with impairment in physiological antioxidant response, lipid peroxidation, nuclear factor kappa-light-chain-enhancer of activated B cells (nf-κb) pathways activation with consequences of pro-inflammatory cytokines release and apoptosis. However, the older group was shown to be more sensitive to ATR inhalation. CONCLUSIONS: our results showed that aged mice were more susceptible compared to young mice to air pollutants exposure, put in place a minor physiologically response was seen when exposed to it.

AQP2 as a target of lycopene protects against atrazine-induced renal ionic homeostasis disturbance.

Atrazine (ATR), a ubiquitous environmental contaminant in water and soil, causes environmental nephrosis. To reveal the toxic effect of ATR on the kidney and the potential chemical nephroprotective effect of lycopene (LYC), Kun-Ming mice of specific pathogen-free (SPF) grade were treated with LYC (5 mg kg-1) and/or ATR (50 mg kg-1 or 200 mg kg-1) for 21 days. The degree of renal injury was evaluated by measuring the ion concentration, ATPase activities and the mRNA expressions/levels of associated ATPase subunits. In addition, the expression of renal aquaporins (AQPs) was analyzed. The results showed that the renal tubular epithelial cells of ATR-exposed mice were swollen, the glomeruli were significantly atrophied, and the ion concentrations were obviously changed. The activity of Na+-K+-ATPase and the transcription of its subunits were downregulated. The activity of Ca2+-Mg2+-ATPase and the transcription of its subunits were upregulated. The expression of AQPs, especially the critical AQP2, was affected. Notably, ATR-induced nephrotoxicity was significantly improved by LYC supplementation. Therefore, LYC could protect the kidney against ATR-induced nephrotoxicity via maintaining ionic homeostasis, reversing the changes in ATPase activity and controlling the expression of AQPs on the cell membrane. These results suggested that AQP2 was a target of LYC and protected against ATR-induced renal ionic homeostasis disturbance.

Developmental atrazine exposure in zebrafish produces the same major metabolites as mammals along with altered behavioral outcomes.

Atrazine (ATZ) is the second most commonly applied agricultural herbicide in the United States. Due to contamination concerns, the U.S. EPA has set the maximum contaminant level in potable water sources at 3 parts per billion (ppb; µg/l). Depending on the time of year and sampling location, water sources often exceed this limit. ATZ is an endocrine disrupting chemical in multiple species observed to target the neuroendocrine system. In this study the zebrafish vertebrate model was used to test the hypothesis that a developmental ATZ exposure generates metabolites similar to those found in mammals and alters morphology and behavior in developing larvae. Adult AB zebrafish were bred, embryos were collected, and exposed to 0, 0.3, 3, or 30 ppb ATZ from 1 to 120 h post fertilization (hpf). Targeted metabolomic analysis found that zebrafish produce the same major ATZ metabolites as mammals: desethyl atrazine (DEA), deisopropyl atrazine (DIA), and diaminochloroatrazine (DACT). The visual motor response test at 120 hpf detected hyperactivity in larvae in the 0.3 ppb treatment group and hypoactivity in the 30 ppb treatment group (p < 0.05). Further analysis into behavior during the dark and light phases showed zebrafish larvae exposed to 0.3 ppb ATZ had an increase in total distance moved in the first light phase and time spent moving in the first dark and light phases (p < 0.05). Alternatively, a decrease in total distance moved was observed in the second and third dark phases in zebrafish exposed to 30 ppb ATZ (p < 0.05). No significant differences were observed for any of the morphological measurements following ATZ exposure from 1 to 120 hpf (p > 0.05). These findings suggest that a ATZ exposure during early development generates metabolite profiles similar to mammals and leads to behavioral alterations supporting ATZ as a neurodevelopmental toxicant.

Carryover effect of atrazine and its metabolite-from treated bovine spermatozoa to the embryo's transcriptome†.

Atrazine (ATZ) is an extensively used herbicide and ubiquitous environmental contaminant. ATZ and its metabolite, diaminochlorotriazine (DACT), cause several cellular and functional alterations in spermatozoa. We aimed to examine the effect of ATZ/DACT on spermatozoon DNA integrity, fertilization competence, embryonic development, and transcriptome profile of in vitro-produced embryos derived from fertilization with pre-exposed sperm. Bovine spermatozoa exposed to ATZ (0.1 or 1 µM) or DACT (1 or 10 µM) during in vitro capacitation were used for in vitro fertilization of untreated oocytes. Cleavage and blastocyst-formation rates were evaluated 42 h and 7 days postfertilization, respectively. The association between DNA fragmentation and apoptosis (annexin V kit) was determined. Fertilization competence of annexin-positive (AV+) and annexin-negative (AV-) spermatozoa was examined. Microarray analysis was performed for 7-day blastocysts. Intracytoplasmic sperm injection was performed with control (AV+, AV-) and DACT (AV+, AV-) spermatozoa. Cleavage rates did not differ between groups and blastocyst formation tended to be higher for AV- vs. AV+ in both control and DACT groups, suggesting that acrosome reaction, rather than DNA fragmentation, underlies the reduced cleavage. Transcriptomic analysis revealed 139 and 230 differentially expressed genes in blastocysts derived from ATZ- and DACT-exposed spermatozoa, respectively, relative to controls. Proteomic analysis shown differential expression of proteins in ATZ- or DACT-treated spermatozoa, in particular proteins related to cellular processes and biological pathways. Therefore, we assume that factors delivered by the spermatozoa, regardless of DNA fragmentation, are also involved. Overall, the current study reveals a deleterious carryover effect of ATZ/DACT from the spermatozoa to the developing embryo.

Embryonic atrazine exposure and later in life behavioral and brain transcriptomic, epigenetic, and pathological alterations in adult male zebrafish.

Atrazine (ATZ), a commonly used pesticide linked to endocrine disruption, cancer, and altered neurochemistry, frequently contaminates water sources at levels above the US Environmental Protection Agency's 3 parts per billion (ppb; µg/L) maximum contaminant level. Adult male zebrafish behavior, brain transcriptome, brain methylation status, and neuropathology were examined to test the hypothesis that embryonic ATZ exposure causes delayed neurotoxicity, according to the developmental origins of health and disease paradigm. Zebrafish (Danio rerio) embryos were exposed to 0 ppb, 0.3 ppb, 3 ppb, or 30 ppb ATZ during embryogenesis (1-72 h post fertilization (hpf)), then rinsed and raised to maturity. At 9 months post fertilization (mpf), males had decreased locomotor parameters during a battery of behavioral tests. Transcriptomic analysis identified altered gene expression in organismal development, cancer, and nervous and reproductive system development and function pathways and networks. The brain was evaluated histopathologically for morphometric differences, and decreased numbers of cells were identified in raphe populations. Global methylation levels were evaluated at 12 mpf, and the body length, body weight, and brain weight were measured at 14 mpf to evaluate effects of ATZ on mature brain size. No significant difference in genome methylation or brain size was observed. The results demonstrate that developmental exposure to ATZ does affect neurodevelopment and neural function in adult male zebrafish and raises concern for possible health effects in humans due to ATZ's environmental presence and persistence. Graphical abstract.

Epigenome-wide association study for atrazine induced transgenerational DNA methylation and histone retention sperm epigenetic biomarkers for disease.

Atrazine is a common agricultural herbicide previously shown to promote epigenetic transgenerational inheritance of disease to subsequent generations. The current study was designed as an epigenome-wide association study (EWAS) to identify transgenerational sperm disease associated differential DNA methylation regions (DMRs) and differential histone retention regions (DHRs). Gestating female F0 generation rats were transiently exposed to atrazine during the period of embryonic gonadal sex determination, and then subsequent F1, F2, and F3 generations obtained in the absence of any continued exposure. The transgenerational F3 generation males were assessed for disease and sperm collected for epigenetic analysis. Pathology was observed in pubertal onset and for testis disease, prostate disease, kidney disease, lean pathology, and multiple disease. For these pathologies, sufficient numbers of individual males with only a single specific disease were identified. The sperm DNA and chromatin were isolated from adult one-year animals with the specific diseases and analyzed for DMRs with methylated DNA immunoprecipitation (MeDIP) sequencing and DHRs with histone chromatin immunoprecipitation (ChIP) sequencing. Transgenerational F3 generation males with or without disease were compared to identify the disease specific epimutation biomarkers. All pathologies were found to have disease specific DMRs and DHRs which were found to predominantly be distinct for each disease. No common DMRs or DHRs were found among all the pathologies. Epimutation gene associations were identified and found to correlate to previously known disease linked genes. This is one of the first observations of potential sperm disease biomarkers for histone retention sites. Although further studies with expanded animal numbers are required, the current study provides evidence the EWAS analysis is effective for the identification of potential pathology epimutation biomarkers for disease susceptibility.

Effect of life stage and pesticide exposure on the gut microbiota of Aedes albopictus and Culex pipiens L.

Pesticides commonly contaminate the aquatic environments inhabited by mosquito juveniles. However, their role in shaping the mosquito microbiota is not well understood. We hypothesized that environmentally relevant concentrations of atrazine, permethrin and malathion will mediate a shift in the mosquito gut bacterial community structure due to their toxic effect on the aquatic bacterial communities, and reduce mosquito gut bacterial diversity by enriching pesticide-degrading bacterial communities over susceptible taxa. Illumina MiSeq sequencing of the V3-V4 hypervariable regions of the 16 S rRNA gene was used to characterize the microbial communities of larval and adult stages of the two mosquito species and the water samples from microcosms treated with each of the pesticides, separately. Bacterial community composition differed by sample type (larval stage vs. adult stage) and water sampling date (day 3 vs. day 7), but not by pesticide treatment. In larval stages, bacterial OTU richness was highest in samples exposed to malathion, intermediate in permethrin, and lowest in controls. Bacterial richness was significantly higher in larval stages compared to adult stages for all treatments. This study provides a primer for future studies evaluating mosquito microbial responses to exposures to chemical pesticides and the possible implications for mosquito ecology.

Adipocyte epigenetic alterations and potential therapeutic targets in transgenerationally inherited lean and obese phenotypes following ancestral exposures.

The incidence of obesity has increased dramatically over the past two decades with a prevalence of approximately 40% of the adult population within the United States. The current study examines the potential for transgenerational adipocyte (fat cell) epigenetic alterations. Adipocytes were isolated from the gonadal fat pad of the great-grand offspring F3 generation 1-year old rats ancestrally exposed to DDT (dichlorodiphenyltrichloroethane), atrazine, or vehicle control in order to obtain adipocytes for DNA methylation analysis. Observations indicate that there were differential DNA methylated regions (DMRs) in the adipocytes with the lean or obese phenotypes compared to control normal (non-obese or lean) populations. The comparison of epigenetic alterations indicated that there were substantial overlaps between the different treatment lineage groups for both the lean and obese phenotypes. Novel correlated genes and gene pathways associated with DNA methylation were identified, and may aid in the discovery of potential therapeutic targets for metabolic diseases such as obesity. Observations indicate that ancestral exposures during critical windows of development can induce the epigenetic transgenerational inheritance of DNA methylation changes in adipocytes that ultimately may contribute to an altered metabolic phenotype.

Atrazine exposure shifts activity but has minimal effects on courtship in an agrobiont spider.

The behavior of many animals relies upon the input of chemical signals throughout the environment. Those animals that live in close proximity to humans may then be at risk, as the input of anthropogenic chemicals can have significant sublethal effects by masking or altering these naturally occurring signals. While the herbicide atrazine has been found to have the potential to alter such chemical information, research is lacking on how it may impact agrobiont arthropods which are the first and most direct line of exposure. Here we investigated the sublethal effects atrazine may be playing on an agrobiont wolf spider that makes up a major component of agricultural spider communities in the Eastern United States. We exposed spiders to ecologically relevant doses of atrazine and monitored general activity patterns as well as mating behaviors. We found that while sex determined a large portion of activity variation in these predators, both males and females spent more time mobile but at lower speeds in the presence of atrazine. We did not find any evidence for info-disruption based on male courtship rate and mating success, but with increasing dosage of atrazine came shortened bouts of courtship leading to copulation. These results suggest that atrazine changed activity patterns of a wolf spider, which may result in altered foraging, survival, and reproduction.

Short term changes in the abundance of nitrifying microorganisms in a soil-plant system simultaneously exposed to copper nanoparticles and atrazine.

Copper nanoparticles (NCu) may co-exist with other pollutants in agricultural soils, such as pesticides. However, this has been little evaluated yet. Thus, possible effects of the simultaneous applications of pesticides and NCu on biogeochemical cycles are expected, for example on the nitrogen cycle. Therefore, the aim of this work was to evaluate the effect of simultaneous application of the herbicide atrazine (ATZ) and NCu on the abundance of total bacteria and nitrifying communities: ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB). Moreover, the ATZ dissipation was evaluated. A soil-plant system containing ATZ at field dose (3 mg a.i. kg-1) was mixed with two doses of NCu (0.05% or 0.15% w/w). Changes in the abundance of 16S rRNA and ammonia monooxygenase (amoA) genes of AOA and AOB were evaluated by real-time quantitative PCR (qPCR) at three sampling times (1, 15 and 30 days). The residual ATZ and nitrate production were also measured. The results showed significant differences in microbial composition and abundance over the 30 days of the experiment. Particularly, an initial decrease was observed in total bacterial abundance due to the presence of ATZ and NCu respect to ATZ alone (~60%). The abundance of AOA was also remarkably reduced (~85%), but these communities gradually recovered towards the end of the experiment. Conversely, AOB abundance initially increased (>100%) and remained mainly unaltered in soil exposed to ATZ and NCu 0.15% w/w, where nitrate formation was also constant. Moreover, NCu decreased the ATZ dissipation, which was translated in a 2-fold increase on the ATZ half-life values (T1/2). This study demonstrates that the simultaneous presence of NCu and ATZ may represent a risk for the total bacteria present in soil and sensitive microorganisms such as nitrifying communities, and changes in the dissipation of the pesticide could influence this process.

Atrazine Exposure Influences Immunity in the Blue Dasher Dragonfly, Pachydiplax longipennis (Odonata: Libellulidae).

Agricultural runoff containing herbicide is known to have adverse effects on freshwater organisms. Aquatic insects are particularly susceptible, and herbicide runoff has the potential to affect immunity in this group. Here we examined the effect of ecologically relevant levels of atrazine, an herbicide commonly used in the United States, on immune function in larvae of the blue dasher dragonfly (Odonata: Libelluludae, Pachydiplax longipennis Burmeister 1839) during a long-term exposure at ecologically relevant concentrations. Larvae were exposed to concentrations of 0, 1, 5, and 10 ppb atrazine for 3 or 6 wk. Hemocyte counts, hemolymph phenyloxidase (PO) activity, cuticular PO, and gut PO were measured at the end of each trial period as indicators of immune system strength. Atrazine concentration had a significant effect on hemocyte counts after controlling for larval size. There was a significant interaction between time and concentration for hemolymph PO, cuticular PO, and a marginal interaction for gut PO. The effect of atrazine on the measured immune parameters was often nonmonotonic, with larger effects observed at intermediate concentrations. Therefore, atrazine affects both hemocyte numbers and PO activity over time in P. longipennis, and the changed immune function demonstrated in this study is likely to modify susceptibility to pathogens, alter wound healing, and may decrease available energy for growth and metamorphosis.

Atrazine-xenobiotic nuclear receptor interactions induce cardiac inflammation and endoplasmic reticulum stress in quail (Coturnix coturnix coturnix).

Atrazine (ATR) is one of the most extensively used herbicide that eventually leaches into groundwater and surface water from agricultural areas. Exposure to ATR does harm to the health of human and animals, especially the heart. However, ATR exposure caused cardiotoxicity in bird remains unclear. To evaluate ATR-exerted potential cardiotoxicity in heart, quail were exposed with 0, 50, 250, and 500 mg/kg BW/day ATR by gavage treatment for 45 days. Cardiac histopathological alternation was observed in ATR-induced quail. ATR exposure increased the Cytochrome P450s and Cytochrome b5 contents, Cytochrome P450 (CYP) enzyme system (APND, ERND, AH, and NCR) activities and the expression of CYP isoforms (CYP1B1, CYP2C18, CYP2D6, CYP3A4, CYP3A7, and CYP4B1) in quail heart. The expression of nuclear xenobiotic receptors (NXRs) was also influenced in the heart by ATR exposure. ATR exposure significantly caused the up-regulation of pro-inflammatory cytokines (TNF-α, IL-6, NF-κB, and IL-8), down-regulation of anti-inflammatory cytokines (IL-10) expression levels and increased NO content and iNOS activity. The present research provides new insights into the mechanism that ATR-induced cardiotoxicity through up-regulating the expression levels of GRP78 and XBP-1s, triggering ER stress, activating the expression of IRE1α/TRAF2/NF-κB signaling pathway related factors (IRE1α, TRAF2, IKK, and NF-κB) and inducing an inflammatory response in quail hearts. In conclusion, ATR exposure could induce cardiac inflammatory injury via activating NXRs responses, disrupting CYP homeostasis and CYP isoforms transcription, altering NO metabolism and triggering ER stress and inflammatory response by activating IRE1α/TRAF2/NF-κB signaling pathway.

Pesticides as risk factors for head and neck cancer: A review.

Humans may be exposed to pesticides such as fungicides, herbicides, and insecticides, during occupational and non-occupational activities. Pesticides could be related to cancer development mainly because of their effects on the endocrine and immune systems and their cumulative effect. The present review evaluated in current literature evidence of an association between exposure to pesticides and the occurrence of head and neck cancer (HNC). A literature search for cohort studies was conducted in the PubMed, Web of science, and Cochrane databases. Methodological quality of each study was rated with the Scottish Intercollegiate Guidelines Network (SIGN) checklist. One thousand one hundred and thirty-two studies were identified. Thirty-two were included. Most of the studies found addressed occupational exposure to pesticides and were conducted in Europe and North America. Eleven high-quality studies were found. Most of them found no association between exposure to pesticides and increased risk of HNC. Two studies found some evidence of a positive association between pesticide (malathion and atrazine) exposure and thyroid cancer. The literature review does not support a clear evidence for association between pesticides exposure and HNC. Only limited evidence points to a positive association between exposure to some pesticides and thyroid cancer. Further standardized studies based on appropriate designs are required to clarify the effect of pesticides on the genesis of HNC, considering dose, length of exposure, and type of pesticide.

The potential protective role of Akropower against Atrazine- induced humoral immunotoxicity in rabbits.

Introduction to the herbicide Atrazine (ATR) can bring about immunotoxicity, aside from other unfavorable results for the creature and human wellbeing. We went for clarifying the genotoxic mechanisms required in humoral immunotoxicity of Gesaprim® (ATR) and their constriction by Akropwer. Forty rabbits (1.5kg±20%) were utilized and appointed into 4 equal groups. group 1: control; group 2: Received Atrazine at 1/10 LD50 via food; group 3: Received Akropwer at 1ml/1l/day by means of drinking water; group 4: Received both Atrazine and Akropwer associatively by the same said dosage and course. Atrazine and Akropower exposure were accomplished for 60days. The genotoxic mechanisms of Atrazine- induced humoral immunotoxicity were explained by increased serum total protein and albumin levels, decreased RHDV antibody titer only after four weeks of vaccination and increased level of spleen Fas and Caspase-III genes expression in Atrazine-exposed rabbits. Marked splenocytes apoptosis were detected in the immunohistochemical examination by caspase-III technique and TUNEL assay. Akropower attenuated ATR-induced apoptosis through down-regulation of Fas and Caspase-III genes expression and suppression of their signaling pathway. In conclusion, induction of apoptosis by overexpression of Fas and Caspase-III genes gives a new insight into the mechanism of ATR immunotoxicity. The protective part of Akropower, on the other hand, was characterized by attenuation of Fas and Caspase-III genes mediated apoptosis.

Changes in bacterial community after application of three different herbicides.

The native soil microbiota is very important to maintain the quality of that environment, but with the intensive use of agrochemicals, changes in microbial biomass and formation of large quantities of toxic waste were observed in soil, groundwater and surface water. Thereby, the goal of this study was to evaluate if the selective pressure exerted by the presence of the herbicides atrazine, diuron and 2,4-D changes the bacterial community structure of an agricultural soil, using denaturing gradient gel electrophoresis technique. According to PERMANOVA analysis, a greater effect of the herbicide persistence time in the soil, the effect of the herbicide class and the effect of interaction between these two factors (persistence time and herbicide class) were observed. In conclusion, the results showed that the selective pressure exerted by the presence of these herbicides altered the composition of the local microbiota, being atrazine and diuron that most significantly affected the bacterial community in soil, and the herbicide 2,4-D was the one that less altered the microbial community and that bacterial community was reestablished first.

Germination of Seeds and Seedling Growth of Amaranthus retroflexus L. Following Sublethal Exposure of Parent Plants to Herbicides.

Herbicides have long-term effects on the vegetative parts and reproduction of plants; however, the carry-over effects of herbicides on the F1 generation of invasive plants remain unclear. The objectives of this work were to investigate the germination and growth of the F1 generation of A. retroflexus, an invasion plant, treated by sublethal herbicides. The results demonstrated that atrazine or tribenuron-methyl had carry-over effects on the F1 generation of A. retroflexus. Atrazine or tribenuron-methyl exposure during the vegetative and reproductive periods significantly inhibited the germination and growth of the F1 generation; a lower sublethal dose of atrazine or tribenuron-methyl did not weaken the inhibition of germination or growth of the F1 generation. Our results suggest that although herbicides have a carry-over inhibition effect on the F1 generation of invasive plants, they may have a more serious carry-over effect on native plants and cause changes in weed species composition and weed diversity.