A combination of silymarin and garlic extract enhances thyroid hormone activation and body metabolism in orally intoxicated male rats with atrazine: Impact on hepatic iodothyronine deiodinase type 1.

Atrazine is a widely applied herbicide to improve crop yield and maintain general health. It has been reported to impair thyroid function and architecture in experimental animals. Alterations in thyroid hormones disrupt normal body function and metabolism. Silymarin, a hepatoprotective flavonolignan, was found to improve thyroid function and body metabolism. Additionally, garlic displays several protective effects on body organs. Therefore, this study explored the prophylactic impact of natural compounds comprising silymarin and garlic extract on disrupted thyroid function, hepatic iodothyronine deiodinase type 1, and metabolic parameters in atrazine-intoxicated male rats. We found that daily pre- and co-treatment of atrazine-intoxicated male rats with silymarin (100 mg/kg, p.o) and/or garlic extract (10 mg/kg, p.o) significantly improved thyroid activation and hepatic functionality as evidenced by the re-establishment of T3, T3/T4, and TSH values as well as ALT and AST activities. Interestingly, individual or concurrent supplementation of the atrazine group with silymarin and garlic extract prevented the down-regulation in hepatic iodothyronine deiodinase type 1. These effects were coupled with the repletion of serum and hepatic antioxidants and the amelioration of lipid peroxidation. In addition, current natural products markedly alleviated weight gain, dyslipidemia, hyperglycemia, glucose intolerance, and insulin resistance. Notably, a cocktail of silymarin and garlic extract exerted superior protection against atrazine-triggered deterioration of thyroid, hepatic, and metabolic functioning to individual treatments. Present findings pinpoint the prophylactic and synergistic influence of silymarin and garlic extract combinatorial regimen on thyroid activation and body metabolism via enhancing antioxidant potential, maintaining hepatic function, and iodothyronine deiodinase type 1.

A mixture of mesotrione and atrazine harms adults and larvae of the predatory wasp Polistes satan.

Herbicides have been intensively used for weed control, raising concerns about their potentially adverse effects on non-target organisms. Research on the effects of these common agrochemicals on beneficial insects and the ecosystem services they provide (e.g., predation and pollination) is scarce. Therefore, we tested whether a commercial formulation comprising a mixture of mesotrione and atrazine was detrimental to adult females and larvae of the Neotropical predatory social wasp Polistes satan, which is an effective natural enemy of crop pests. Wasps were individually fed syrups contaminated with different concentrations of the herbicide above and below the maximum label rate (MLR = 12 mL/L). Survival was assessed. The locomotor activity, immune response, and midgut morphology of adults as well as the immune response of the larvae were also studied. Herbicide concentrations far above the MLR (12, 40, and 100 times) caused adult mortality, whereas lower concentrations (0.5, 1, and 6 times) did not. Herbicide exposure at 0.5 to 12 times the MLR increased adult activity. Adult exposure at 0.1 or 0.5 times the MLR did not affect melanotic encapsulation of foreign bodies but led to changes in the morphology of the midgut epithelium and peritrophic matrix. In larvae, the ingestion of herbicide at 0.1 or 0.2 times the MLR (corresponding to 9.6 and 19.2 ng of herbicide per individual) did not cause mortality but decreased their melanization-encapsulation response. Increased locomotor activity in herbicide-exposed adults can affect their foraging activity. The altered midgut morphology of adults coupled with the decreased immune response in larvae caused by herbicide exposure at realistic concentrations can increase the susceptibility of wasps to infections. Therefore, herbicides are toxic to predatory wasps.

Effects of atrazine and S-metolachlor on stream periphyton taxonomic and fatty acid compositions.

Extensive pesticide use for agriculture can diffusely pollute aquatic ecosystems through leaching and runoff events and has the potential to negatively affect non-target organisms. Atrazine and S-metolachlor are two widely used herbicides often detected in high concentrations in rivers that drain nearby agricultural lands. Previous studies focused on concentration-response exposure of algal monospecific cultures, over a short exposure period, with classical descriptors such as cell density, mortality or photosynthetic efficiency as response variables. In this study, we exposed algal biofilms (periphyton) to a concentration gradient of atrazine and S-metolachlor for 14 days. We focused on fatty acid composition as the main concentration-response descriptor, and we also measured chlorophyll a fluorescence. Results showed that atrazine increased cyanobacteria and diatom chlorophyll a fluorescence. Both herbicides caused dissimilarities in fatty acid profiles between control and high exposure concentrations, but S-metolachlor had a stronger effect than atrazine on the observed increase or reduction in saturated fatty acids (SFAs) and very long-chain fatty acids (VLCFAs), respectively. Our study demonstrates that two commonly used herbicides, atrazine and S-metolachlor, can negatively affect the taxonomic composition and fatty acid profiles of stream periphyton, thereby altering the nutritional quality of this resource for primary consumers.

Early and transitory hypoactivity and olfactory alterations after chronic atrazine exposure in female Sprague-Dawley rats.

Several studies have shown that chronic exposure to the herbicide atrazine (ATR) causes alterations in locomotor activity and markers of the dopaminergic systems of male rats. However, few studies have evaluated the sex-dependent effects of atrazine exposure. The aim of the present study was to evaluate whether chronic ATR exposure causes alterations in behavioral performance and dopaminergic systems of female rats. At weaning, two groups of rats were exposed to 1 or 10 mg ATR/kg body weight daily thorough the food, while the control group received food without ATR for 14 months. Spontaneous locomotor activity was evaluated monthly for 12 months, while anxiety, egocentric and spatial memory, motor coordination, and olfactory function tasks were evaluated between 13 and 14 months of ATR exposure. Tyrosine hydroxylase (TH) and monoamine content in brain tissue were assessed at the end of ATR treatment. Female rats treated with 1 or 10 mg ATR showed vertical hypoactivity compared to the control group only in the first month of ATR exposure. Impairments in olfactory functions were found due to ATR exposure. Nevertheless, no alterations in anxiety, spatial and egocentric memory, or motor coordination tasks were observed, while the levels of TH and dopamine and its metabolites in brain tissue were similar among groups. These results suggest that female rats could present greater sensitivity to the neurotoxic effects of ATR on spontaneous locomotor activity in the early stages of development. However, they are unaffected by chronic ATR exposure later in life compared to male rats. More studies are necessary to unravel the sex-related differences observed after chronic ATR exposure.

MAPK/NF-κB signaling mediates atrazine-induced cardiorenal syndrome and antagonism of lycopene.

Atrazine (ATZ) is the most prevalent herbicide that has been widely used in agriculture to control broadleaf weeds and improve crop yield and quality. The heavy use of ATZ has caused serious environmental pollution and toxicity to human health. Lycopene (LYC), is a carotenoid that exhibits numerous health benefits, such as prevention of cardiovascular diseases and nephropathy. However, it remains unclear that whether ATZ causes cardiorenal injury or even cardiorenal syndrome (CRS) and the beneficial role of LYC on it. To test this hypothesis, mice were treated with LYC and/or ATZ for 21 days by oral gavage. This study demonstrated that ATZ exposure caused cardiorenal morphological alterations, and several inflammatory cell infiltrations mediated by activating NF-κB signaling pathways. Interestingly, dysregulation of MAPK signaling pathways and MAPK phosphorylation caused by ATZ have been implicated in cardiorenal diseases. ATZ exposure up-regulated cardiac and renal injury associated biomarkers levels that suggested the occurrence of CRS. However, these all changes were reverted, and the phenomenon of CAR was disappeared by LYC co-treatment. Based on our findings, we postulated a novel mechanism to elucidate pesticide-induced CRS and indicated that LYC can be a preventive and therapeutic agent for treating CRS by targeting MAPK/NF-κB signaling pathways.

Effects of atrazine and curcumin exposure on TCMK-1 cells: Oxidative damage, pyroptosis and cell cycle arrest.

Atrazine (ATR), a commonly used herbicide, is highly bioaccumulative and toxic, posing a threat to a wide range of organisms. Curcumin has strong antioxidant properties. However, it is unclear whether curcumin counteracts cellular pyroptosis as well as cell cycle arrest induced by ATR exposure. Therefore, we conducted a study using TCMK-1 cells and established cell models by adding 139 µmol/L ATR and 20 µmol/L curcumin. The results showed that ATR exposure produced excessive reactive oxygen species (ROS), reduced activities of enzymes such as GSH-PX, SOD and Total Antioxidant Capacity, markedly increased the content of H2O2, disrupted the antioxidant system, activated Caspase-1, and the expression levels of the pyroptosis-related genes NLRP3, GSDMD, ASC, Caspase-1, IL-1ß and IL-18 were increased. The simultaneous excess of ROS led to DNA damage, activation of P53 led to elevated expression levels of P53 and P21, as a consequence, the expression levels of cyclinE, CDK2 and CDK4 were reduced. These results suggest that Cur can modulate ATR exposure-induced pyroptosis as well as cell cycle arrest in TCMK-1 cells by governing oxidative stress.

Effects of herbicides and fertilization on biofilms of Pampean lotic systems: A microcosm study.

We experimentally assessed the impact of the application of herbicides and fertilizers derived from agricultural activity through the individual and simultaneous addition of glyphosate, atrazine, and nutrients (nitrogen 'N' and phosphorus 'P') on the biofilm community and their resilience when the experimental factors were removed. We hypothesize that i) the presence of agrochemicals negatively affects the biofilm community leading to the simplification of the community structure; ii) the individual or simultaneous addition of herbicides and nutrients produces differential responses in the biofilm; and iii) the degree of biofilm recovery differs according to the treatment applied. Environmentally relevant concentrations of glyphosate (0.7 mgL-1), atrazine (44 µgL-1), phosphorus (1 mg P L-1 [KH2PO4]), and nitrogen (3 mg N L-1[NaNO3]) were used. Chlorophyll a, ash-free dry weight, abundance of main biofilm groups and nutrient contents in biofilm were analyzed. At initial exposure time, all treatments were dominated by Cyanobacteria; through the exposure period, it was observed a progressive replacement by Bacillariophyceae. This replacement occurred on day 3 for the control and was differentially delayed in all herbicides and/or nutrient treatments in which the abundance of cyanobacteria remains significant yet in T5. A significant correlation was observed between the abundance of cyanobacteria and the concentration of atrazine, suggesting that this group is less sensitive than diatoms. The presence of agrochemicals exerted differential effects on the different algal groups. Herbicides contributed to phosphorus and nitrogen inputs. The most frequently observed interactions between experimental factors (nutrients and herbicides) was additivity excepting for species richness (antagonistic effect). In the final recovery time, no significant differences were found between the treatments and the control in most of the evaluated parameters, evincing the resilience of the community.

Biological-based techniques for real-time water-quality studies: Assessment of non-invasive (swimming consistency and respiration) and toxicity (antioxidants) biomarkers of zebrafish.

Swimming consistency and respiration of fish are recognized as the non-invasive stress biomarkers. Their alterations could directly indicate the presence of pollutants in the water ecosystem. Since these biomarkers are a routine process for fish, it is difficult to monitor their activity manually. For this reason, experts employ engineering technologies to create sensors that can monitor the regular activities of fish. Knowing the importance of these non-invasive stress biomarkers, we developed online biological behavior monitoring system-OBBMS and online biological respiratory response monitoring system-OBRRMS to monitor real-time swimming consistency and respiratory response of fish, respectively. We continuously monitored the swimming consistency and respiration (OCR, CER and RQ) of zebrafish (control and atrazine-treatments) for 7 days using our homemade real-time biological response monitoring systems. Furthermore, we analyzed oxidative stress indicators (SOD, CAT and POD) within the vital tissues (gills, brain and muscle) of zebrafish during stipulated sampling periods. The differences in the swimming consistency and respiratory rate of zebrafish between the control and atrazine treatments could be precisely differentiated on the real-time datasets of OBBMS and OBRRMS. The zebrafish exposed to atrazine toxin showed a concentration-dependent effect (hypoactivity). The OCR and CER were increased in the atrazine treated zebrafish. Both Treatment I and II received a negative response for RQ. Atrazine toxicity let to a rise in the levels of SOD, CAT and POD in the vital tissues of zebrafish. The continuous acquisition of fish signals is achieved which is one of the main merits of our OBBMS and OBRRMS. Additionally, no special data processing was done, the real-time data sets were directly used on statistical tools and the differences between the factors (groups, photoperiods, exposure periods and their interactions) were identified precisely. Hence, our OBBMS and OBRRMS could be a promising tool for biological response-based real-time water quality monitoring studies.

Peripubertal exposure of atrazine cause decrease in exploratory activity, deficits in sociability and few alterations on brain monoaminergic systems of rats.

Atrazine is a pesticide used to control weeds in both in pre- and post-emergence crops. The chronic exposure to atrazine can lead to severe damage in animals, especially in the endocrine and reproduction systems, leading to the inclusion of this pesticide into the endocrine disrupting chemicals group. Studies with rats showed that atrazine exposure during lactation in dams caused changes in the juvenile offspring, however; there is still limited information regarding the effects of atrazine during puberty. Thus, the aim of this study is to evaluate the effects of peripubertal exposure of atrazine in rats, assessing motor activity, social behavior and neurochemical alterations. Juvenile rats were treated with different doses of atrazine (0, 10, 30 or 100 mg/kg) by gavage from postnatal day 22 to 41. Behavioral tests were conducted for the evaluation of motor activity and social behavior, and neurochemical evaluation was done in order to assess monoamine levels. Atrazine caused behavioral alterations, evidenced by decrease in the exploratory activity (p values variation between 0.05 and 0.0001) and deficits in the social behavior of both male and females as adults (p values variation between 0.01 and 0.0001). As for the monoaminergic neurotransmission, atrazine led to very few alterations on the dopamine and serotonin systems that were limited to the females (p < 0.05). Altogether, the results suggests that peripubertal exposure of atrazine cause behavioral and neurochemical alterations. More studies need to be conducted to fully understand the differences in atrazine's effects and its use should be considered carefully.

Exposure to atrazine by drinking water and the increased risk of neonatal complications in consequence: a meta-analysis.

This meta-analysis evaluates the association between atrazine (ATR) exposure and small for gestational age (SGA), preterm birth (PTB), and low birth weight (LBW). A comprehensive search was done on academic databases (e.g. PubMed, Scopus, Embase, and Google Scholar) to achieve all pertinent studies up to May 2023. A pooled odd ratio (OR) and corresponding 95% confidence interval (CI) were applied to evaluate this correlation. As a result, five eligible studies met the inclusion criteria and were included in our study, and the result of the present meta-analysis showed that ATR exposure increased the risk of SGA (OR = 1.11; 95% CI = 1.03-1.20 for highest versus lowest category of ATR), PTB (OR = 1.16; 95% CI = 1.03-1.30), and LBW (OR = 1.26; 95% CI = 1.10-1.44). This meta-analysis suggests that ATR in drinking water may be a risk factor for SGA, PTB, and LBW.

The ROS/SIRT1/STAR axis as a target for melatonin ameliorating atrazine-induced mitochondrial dysfunction and steroid disorders in granulosa cells.

The granulosa cells (GCs) of birds are essential for the reproduction and maintenance of populations in nature. Atrazine (ATR) is a potent endocrine disruptor that can interfere with reproductive function in females and Diaminochlorotriazine (DACT) is the primary metabolite of ATR in the organism. Melatonin (MT) is an endogenous hormone with antioxidant properties that plays a crucial role in development of animal germ cells. However, how ATR causes mitochondrial dysfunction, abnormal secretion of steroid hormones, and whether MT prevents ATR-induced female reproductive toxicity remains unclear. Thus, the purpose of this study is to investigate the protective effect of MT against ATR-induced female reproduction. In the present study, the GCs of quail were divided into 6 groups, as follows: C (Serum-free medium), MT (10 µM MT), A250 (250 µM ATR), MA250 (10 µM MT+250 µM ATR), D200 (200 µM DACT) and MD200 (10 µM MT+200 µM DACT), and were cultured for 24 h. The results revealed that ATR prevented GCs proliferation and decreased cell differentiation. ATR caused oxidative damage and mitochondrial dysfunction, leading to disruption of steroid synthesis, which posed a severe risk to GC's function. However, MT supplements reversed these changes. Mechanistically, our study exhibited that the ROS/SIRT1/STAR axis as a target for MT to ameliorate ATR-induced mitochondrial dysfunction and steroid disorders in GCs, which provides new insights into the role of MT in ATR-induced reproductive capacity and species conservation in birds.

Melatonin inhibits atrazine-induced mitochondrial impairment in cerebellum of mice: Modulation of cGAS-STING-NLRP3 axis-dependent cell pyroptosis.

The global prevalence of Neurological disorders has increased alarmingly in response to environmental and lifestyle changes. Atrazine (ATZ) is a difficult to degrade soil and water pollutant with well-known neurotoxicity. Melatonin (MT), an antioxidant with chemoprotective properties, has a potential therapeutic effect on cerebellar damage caused by ATZ exposure. The aim of this study was to explore the effects and underlying mechanisms of MT on the cerebellar inflammatory response and pyroptosis induced by ATZ exposure. In this study, C57BL/6J mice were treated with ATZ (170 mg/kg BW/day) and MT (5 mg/kg BW/day) for 28 days. Our results revealed that MT alleviated the histopathological changes, ultrastructural damage, oxidative stress and decrease of mitochondrial membrane potential (ΔΨm) in the cerebellum induced by ATZ exposure. ATZ exposure damaged the mitochondria leading to release of mitochondrial DNA (mtDNA) to the cytoplasm, MT activated the cyclic GMP-AMP synthetase interferon gene stimulator (cGAS-STING) axis to alleviate inflammation and pyroptosis caused by ATZ exposure. In general, our study provided new evidence that the cGAS-STING-NLRP3 axis plays an important role in the treatment of ATZ-induced cerebellar injury by MT.

Atrazine exposure caused oxidative stress in male rats and inhibited brain-pituitary-testicular functions.

Exposure to the herbicide atrazine has been shown to have deleterious effects on human and animal reproduction. To determine whether atrazine influences the brain-pituitary-testicular axis directly or indirectly, the present study examined the toxic effects of atrazine on fertility potential by assessing gonadal hormones, testicular function indices, sperm quality, and oxido-inflammatory markers in rats. Twelve animals were grouped into two groups; control and atrazine. The control group received oral administration of olive oil (2 mL/kg), while the atrazine group received 120 mg/kg of atrazine. Treatments were daily and lasted for 7 days. Upon treatment cessation, rats were necropsied for biochemical and histopathological analyses. The biochemical function indices in the rat brain, testis, and epididymis decreased significantly in the atrazine group. Atrazine exposure led to decreases in gonadal hormonal concentrations, semen quality parameters, and testicular function indices compared with the control. Furthermore, there was a marked increase in oxidative stress and inflammatory markers as well as degeneration of the histo-architecture in atrazine-treated rats. Overall, atrazine exposure impaired sperm quality, led to increased inflammation and oxidative stress, and decreased the activity of the brain-pituitary-testicular axis via endocrine disruption.

Testosterone restores TM3 and TM4 cell viability, reduces reactive oxygen species generation, and protects against atrazine-induced stereological changes in rat testes.

In this study, we performed the stereological examination of rat testes and evaluated the protective effect of testosterone against atrazine (ATZ) toxicity in TM3 Leydig and TM4 Sertoli cells. Testosterone intake in rats increased the volumetric density of the seminiferous tubules; tubular diameter; germinal epithelial height; number of spermatogonia, primary and secondary spermatocytes, round spermatids, Sertoli cells, and Leydig cells; and Johnsen scores compared with the values after ATZ treatment (p < 0.05). Furthermore, testosterone increased the viability of TM3 cells and reduced reactive oxygen species (ROS) generation in TM4 cells compared to the ATZ-treated group. In conclusion, exogenous testosterone intake maintains testicular morphometry and spermatogenesis in rats, and minimizes cell death and ROS generation in testicular cell lines exposed to ATZ. However, TM4 cells are more responsive to testosterone-mediated regulation of ROS generation induced by ATZ than TM3 cells.

Elevated parkinsonism pathological markers in dopaminergic neurons with developmental exposure to atrazine.

Atrazine (ATZ) is one of the most used herbicides in the US and a known endocrine disruptor. ATZ is frequently detected in drinking water, especially in Midwestern regions of the United States, exceeding the EPA regulation of maximum contamination level (MCL) of 3 ppb. Epidemiology studies have suggested an association between ATZ exposure and neurodegeneration. Less, however, is known about the neurotoxic mechanism of ATZ, particularly for exposures at a developmental stage. Here, we exposed floor plate progenitors (FPPs) derived from human induced pluripotent stem cells (hiPSCs) to low concentrations of ATZ at 0.3 and 3 ppb for two days followed by differentiation into dopaminergic (DA) neurons in ATZ-free medium. We then examined the morphology, activity, pathological protein aggregation, and transcriptomic changes of differentiated DA neurons. We observed significant decrease in the complexity of neurite network, increase of neuronal activity, and elevated tau- and α-synuclein (aSyn) pathologies after ATZ exposure. The ATZ-induced neuronal changes observed here align with pathological characteristics in Parkinson's disease (PD). Transcriptomic analysis further corroborates our findings; and collectively provides a strong evidence base that low-concentration ATZ exposure during development can elicit increased risk of neurodegeneration.

Understanding atrazine elimination via treatment of the enzyme-based Fenton reaction: Kinetics, mechanism, reaction pathway, and metabolites toxicity.

The degradation kinetics and mechanism of atrazine (ATZ) via an enzyme-based Fenton reaction were investigated at various substrate concentrations and pH values. Toxicological assessment was conducted on ATZ and its degradation products, and the associated reaction pathway was examined. The in situ production of hydrogen peroxide (H2O2) was monitored within the range of 3-15 mM, depending on the increase in glucose concentration, while decreasing the pH to 3.2-5.1 (initial pH of 5.8) or 6.5-7.4 (initial pH of 7.7). The degradation efficiency of ATZ was approximately 2-3 times higher at an initial pH of 5.8 with lower glucose concentrations than at an initial pH of 7.7 with higher substrate concentrations during the enzyme-based Fenton reaction. The apparent pseudo-first-order rate constant for H2O2 decomposition under various conditions in the presence of ferric citrate was 1.9-6.3 × 10-5 s-1. The •OH concentration ([•OH]ss) during the enzyme-based Fenton reaction was 0.5-4.1 × 10-14 M, and the second-order rate constant for ATZ degradation was 1.5-3.3 × 109 M-1 s-1. ATZ intrinsically hinders the growth and development of Arabidopsis thaliana, and its inhibitory effect is marginal, depending on the reaction time of the enzyme-based Fenton process. The ATZ transformation during this process occurs through dealkylation, hydroxylation, and dechlorination via •OH-mediated reactions. The degradation kinetics, mechanism, and toxicological assessment in the present study could contribute to the development and application of enzyme-based Fenton reactions for in situ pollutant abatement. Moreover, the enzyme-based Fenton reaction could be an environmentally benign and applicable approach for eliminating persistent organic matter, such as herbicides, using diverse H2O2-producing microbes and ubiquitous ferric iron with organic complexes.

Holistic Assessment Based On Hepatocyte Mitochondria: Lycopene Repairs Oxidized mtDNA to Alleviate Mitochondrial Stress Induced by Atrazine.

Atrazine (ATZ) is a highly persistent herbicide that harms organism health. Lycopene (LYC) is an antioxidant found in plants and fruits. The aim of this study is to investigate the mechanisms of atrazine-induced mitochondrial damage and lycopene antagonism in the liver. The mice were divided into seven groups by randomization: blank control (Con group), vehicle control (Vcon group), 5 mg/kg lycopene (LYC group), 50 mg/kg atrazine (ATZ1 group), ATZ1+LYC group, 200 mg/kg atrazine (ATZ2 group), and ATZ2+LYC group. The present study performed a holistic assessment based on mitochondria to show that ATZ causes the excessive fission of mitochondria and disrupts mitochondrial biogenesis. However, the LYC supplementation reverses these changes. ATZ causes increased mitophagy and exacerbates the production of oxidized mitochondrial DNA (Ox-mtDNA) and mitochondrial stress. This study reveals that LYC could act as an antioxidant to repair Ox-mtDNA and restore the disordered mitochondrial function caused by ATZ.

Effect of atrazine on testicular toxicity involves accommodative disorder of xenobiotic metabolizing enzymes system and testosterone synthesis in European quail (Coturnix coturnix).

Due to the wide use of atrazine (ATR), the concern has increased regarding the negative impact of ATR on reproduction. Nevertheless, the reproductive effects caused by different exposure concentrations and the severity of toxic damage are poorly understood. In organisms, ATR is metabolized and degraded through phase II enzyme systems, and changes in cytochrome P450 (CYP) enzymes may have a regulatory role in the harm of ATR. However, less information is available on the induction of CYPs by ATR in avian organisms, and even less on its effects on the testis. Birds are exposed to ATR mainly through food residues and contaminated water, the purpose of this study was to examine reproductive toxicity by different exposure concentrations and elaborate metabolic disorders caused by ATR in European quail (Coturnix coturnix). In this study, the quail were given ATR at 50 mg/kg, 250 mg/kg and 500 mg/kg by oral gavage for 45 days, and the testicular weight coefficients, histopathology and ultrastructure of testes, primary biochemical functions, sex steroid hormones, critical protein levels in the testosterone synthesis pathway, the expression of genes involved CYPs, gonad axis and nuclear receptors expression were investigated. Altogether, testicular coefficient decreased significantly in the high-dose group (1.22%) compared with the control group (3.03%) after 45 days of ATR exposure, and ATR is a potent CYP disruptor that acts through the NXRs and steroid receptor subfamily (APND, CAR, ERND and ERα) without a dose-dependent manner. Notably, ATR interfered with the homeostasis of hormones by triggering the expression of hormones on the gonad axis (LH and E2). These results suggest that exposure to ATR can cause testicular toxicity involving accommodative disorder of phase II enzyme and testosterone synthesis in European quail.

Unraveling the combined deleterious effects of ochratoxin A and atrazine upon broiler's health: Toxicopathological, serum biochemical and immunological perspectives.

Atrazine, a herbicide, is used for eradication of broad-leaved herbs in corn crop; and ochratoxins, particularly ochratoxin A (OTA), are major pollutants of poultry diet. Existence of both of these hazardous chemicals as residues is obvious as elucidated by various epidemiological findings. The present study was designed to investigate toxicopathological, serum biochemical and immunological alterations incurred by atrazine alone and/or, in combination with OTA in broilers. For this purpose, one-day old broiler chicks (n = 180) were purchased from a local hatching unit and were fed two levels of atrazine (50 and 150 mg/kg) and one level of OTA (100 µg/kg) in different combinations. Results of this experiment showed a significant reduction in feed intake, body weight gain, relative organ weights, serum total protein, albumin and globulin while there was a significant increase in urea and creatinine levels, decreased antibody response to sheep red blood cells, reduced lymphoproliferative response and phagocytic capacity in groups given OTA and atrazine individually in feed and these effects became more pronounced when atrazine was given in combination with OTA suggesting synergistic effects of both toxicants for each other.

Adverse developmental impacts in progeny of zebrafish exposed to the agricultural herbicide atrazine during embryogenesis.

Atrazine (ATZ) is an herbicide commonly used on crops in the Midwestern US and other select global regions. The US Environmental Protection Agency ATZ regulatory limit is 3 parts per billion (ppb; µg/L), but this limit is often exceeded. ATZ has a long half-life, is a common contaminant of drinking water sources, and is indicated as an endocrine disrupting chemical in multiple species. The zebrafish was used to test the hypothesis that an embryonic parental ATZ exposure alters protein levels leading to modifications in morphology and behavior in developing progeny. Zebrafish embryos (F1) were collected from adults (F0) exposed to 0, 0.3, 3, or 30 ppb ATZ during embryogenesis. Differential proteomics, morphology, and behavior assays were completed with offspring aged 120 or 144 h with no additional chemical treatment. Proteomic analysis identified differential expression of proteins associated with neurological development and disease; and organ and organismal morphology, development, and injury, specifically the skeletomuscular system. Head length and ratio of head length to total length was significantly increased in the F1 of 0.3 and 30 ppb ATZ groups (p < 0.05). Based on molecular pathway alterations, further craniofacial morphology assessment found decreased distance for cartilaginous structures, decreased surface area and distance between saccular otoliths, and a more posteriorly positioned notochord (p < 0.05), indicating delayed ossification and skeletal growth. The visual motor response assay showed hyperactivity in progeny of the 30 ppb treatment group for distance moved and of the 0.3 and 30 ppb treatment groups for time spent moving (p < 0.05). Due to the changes in saccular otoliths, an acoustic startle assay was completed and showed decreased response in the 0.3 and 30 ppb treatments (p < 0.05). These findings suggest that a single embryonic parental exposure alters cellular pathways in their progeny that lead to perturbations in craniofacial development and behavior.