Agricultural workplaces consist of multiple airborne contaminants and inhalation exposures induce respiratory effects in workers. Endotoxin (LPS) and glyphosate are two common airborne contaminants ...in agricultural environments. We have previously shown that exposure to a combination of LPS and glyphosate synergistically modulates immune reactions as compared to individual exposures. The immunopathogenesis of acute and chronic exposure to complex agricultural exposures including LPS and glyphosate is not known; therefore, we further investigated the lung cellular inflammatory differences in mice exposed to either a combination, or individual, LPS, and glyphosate for 1 day, 5 days, and 10 days. Exposure to a combination of LPS and glyphosate resulted in greater cellular inflammatory effects in lungs as compared to individual exposures to LPS or glyphosate. Repeated exposures to the combination of LPS and glyphosate resulted in robust infiltration of inflammatory cells in the perivascular, peribronchiolar, and alveolar regions, and increases of alveolar septal thicknesses and perivascular spaces in the lungs with intense intercellular adhesion molecule (ICAM) − 1 staining in the perivascular region, but minimal staining in the pulmonary artery endothelium.
Ethion, an organophosphorus pesticide, is used worldwide and has potential for toxicity and inflammation. There are very limited data on the pulmonary and genotoxic effects of ethion especially when ...the exposure is combined with lipopolysaccharide. Therefore, we used a mouse model to test the hypothesis that prolonged exposure to ethion alone or in conjunction with lipopolysaccharide (LPS) will cause lung inflammation and genotoxicity in a mouse model. Swiss albino (
n
= 30) were divided into a control (
n
= 10) and two treatment groups (
n
= 10; each group). The treatment groups were orally administered ethion (4 or 2 mg/kg/animal/day;
n
= 10 each) dissolved in corn oil for 90 days. After 90 days of exposure, five animals from each of the groups were challenged with 80 μg
Escherichia coli
lipopolysaccharide (LPS) intranasally and the remaining five animals with normal saline solution via the same route. Ethion at both dosages induced lung inflammation as indicated by increased (
p
< 0.05) perivascular and peribronchial accumulation of inflammatory cells along with thickening of the alveolar septal wall. Ethion at 4 mg/kg altered (
p
< 0.05) the mRNA and protein expression of TLR-9 and IL-1β in the lungs and induced genotoxicity in blood cells as determined by single cell gel electrophoresis (Comet assay). Further, both dosages of ethion in combination with
E. coli
LPS caused genotoxicity and increased (
p
< 0.05) pulmonary expression of TLR-4, TLR-9 and IL-1β. The data taken together suggest ethion induces lung inflammation and interaction between ethion and LPS increases genotoxicity in blood cells.
In the present study, we used high-throughput sequencing, miRNA-seq, to discover and explore the expression profiles of known and novel miRNAs in TLR ligand-stimulated vis-à-vis non-stimulated (i.e. ...Control) peripheral blood mononuclear cells (PBMCs) isolated from blood of healthy Murrah buffaloes. Six small RNA (sRNA) libraries were multiplexed in Ion Torrent PI chip and sequenced on Ion Proton System. The reads obtained were aligned to the Bos taurus genome (UMD3.1 assembly), which is phylogenetically closest species to buffalo (Bubalus bubalis). A total of 160 bovine miRNAs were biocomputationally identified in buffalo PBMCs and 130 putatively novel miRNAs (not enlisted in the bovine mirBase) were identified. All of these 290 miRNAs identified across the six treatment and control samples represent the repertoire of novel miRNAs for the buffalo species. The expression profiles of these miRNAs across the samples have been represented by sample dendrogram and heatmap plots. The uniquely expressed miRNAs in each treatment and control groups were identified. A few miRNAs were expressed at very high levels while the majority of them were moderately expressed. The miRNAs bta-miR-103 and -191 were found to be highly abundant and expressed in all the samples. Other abundantly expressed miRNAs include bta-miR-19b, -29b, -15a, -19a, -30d, -30b-5p and members of let family (let 7a-5p, let 7g & let 7f) in LPS and CpG treated PBMCS and bta-miR-191, -103 & -19b in Poly I:C stimulated PBMCs. Only one novel miRNA (bta-miR-11039) out of 130 identified putatively novel miRNAs, was expressed in all the six samples and differentially expressed (>2- fold) miRNAs were identified. Six of the differentially expressed miRNAs across the groups (bta-miR-421, bta-let-7i, bta-miR-138, bta-miR-21-5p, bta-miR-222 and bta-miR-27b) were subsequently confirmed by TaqMan quantitative reverse transcription polymerase chain reaction (qRT-PCR). Furthermore, the target genes of differentially expressed miRNAs were enriched for the roles in innate immunity and TLR signaling pathways. This maiden study on profiling and cataloguing of bubaline miRNAs expressed in TLR-ligand stimulated PBMCs will provide an important reference point for future studies on regulatory roles of miRNAs in immune system of buffaloes.
The use of engineered nanomaterials (ENMs) for environmental remediation, known as nanoremediation, represents a challenging and innovative solution, ensuring a quick and efficient removal of ...pollutants from contaminated sites. Although the growing interest in nanotechnological solutions for pollution remediation, with significant economic investment worldwide, environmental and human risk assessment associated with the use of ENMs is still a matter of debate and nanoremediation is seen yet as an emerging technology. Innovative nanotechnologies applied to water and soil remediation suffer for a proper environmental impact scenario which is limiting the development of specific regulatory measures and the exploitation at European level. The present paper summarizes the findings from the workshop: “Ecofriendly Nanotechnology: state of the art, future perspectives and ecotoxicological evaluation of nanoremediation applied to contaminated sediments and soils” convened during the Biannual ECOtoxicology Meeting 2016 (BECOME) held in Livorno (Italy). Several topics have been discussed and, starting from current state of the art of nanoremediation, which represents a breakthrough in pollution control, the following recommendations have been proposed: (i) ecosafety has to be a priority feature of ENMs intended for nanoremediation; ii) predictive safety assessment of ENMs for environmental remediation is mandatory; (iii) greener, sustainable and innovative nano-structured materials should be further supported; (iii) those ENMs that meet the highest standards of environmental safety will support industrial competitiveness, innovation and sustainability. The workshop aims to favour environmental safety and industrial competitiveness by providing tools and modus operandi for the valorization of public and private investments.
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•Nanotechnology represents a breakthrough for environmental remediation.•Ecosafety is a priority feature of ENMs intended for nanoremediation.•Predictive safety assessment of ENMs for environmental remediation is mandatory.•Greener and sustainable (nano) solutions are emerging.•Regulatory framework will support industrial competitiveness of the sector.
Glyphosate is an active ingredient in herbicides. Exposure to glyphosate-based herbicides has been associated with respiratory dysfunctions in agricultural workers. The ability of inhaled glyphosate ...to induce lung inflammation is not well understood. Further, the role of adhesion molecules in glyphosate-induced lung inflammation has not been studied. We evaluated lung inflammatory responses from single and repeated glyphosate exposures. Male C57BL/6 mice were intranasally exposed to glyphosate (1 μg/40 μL) for 1 day or once daily for 5 days or 10 days. Lung tissue and bronchoalveolar lavage (BAL) fluid were collected and analyzed. Repeated exposure to glyphosate for 5 days and 10 days resulted in an increase in neutrophils in BAL fluid and higher eosinophil peroxidase levels in lungs, with leukocyte infiltration further confirmed through lung histology. Repetitive exposure to glyphosate increased IL-33 and Th2 cytokines IL-5 and IL-13. A single glyphosate treatment revealed expression for ICAM-1, VCAM-1, and vWF adhesion molecules in the perivascular region of lung sections; with repeated treatment (5 and 10 days), adhesion molecule expression was found in the perivascular, peribronchiolar, and alveolar regions of the lungs. Repetitive exposure to glyphosate induced cellular inflammation in which adhesion molecules may be important to the lung inflammatory process.
A 7-year-old male with a history of blunt trauma to the abdomen and diagnosis of perinephric hematoma in contrast-enhanced computed tomography (CT) presented with increasing peri-nephric collection ...(after ~1.5 months) in the serial ultrasound examinations. The patient was referred to the department of nuclear medicine for the assessment of this collection as well as renal function. In 99mTc-diethylenetriamine pentaacetate renal scintigraphy, progressively increasing radiotracer activity was noted inferolaterally to the left kidney, separated from the same by a photopenic area. Single-photon emission computed tomography/CT revealed a peri-nephric urinoma in relation to the previously diagnosed hematoma at the lower pole; which was communicating with the pelvi-calyceal system (PCS). Not only did the renal scintigraphy aid in the diagnosis of urinoma but it was also able to show that it was communicating freely with the PCS and that the rest of the renal parenchyma was functioning adequately. This multi-faceted assessment in a single investigation allowed clinicians to opt for the conservative management despite the increasing size of urinoma in the early follow-up.
Background Pesticide residues in food and environment along with airborne contaminants like endotoxins pose a tangible threat to living beings. Fipronil, a broad-spectrum insecticide at acute doses ...in combination with endotoxin has been linked to airway inflammation. Wnt/PCP pathway plays important role in the pathogenesis of chronic inflammatory conditions by contributing to the release of downstream cytokines. However, there is no data on the PCP signaling pathway during fipronil-induced lung damage. This study aims to understand the molecular mechanisms underlying the pulmonary toxicity induced by fipronil alone or in combination with endotoxin. Methods We used a microarray approach to obtain a global view of the transcriptional responses of the lungs exposed to fipronil and endotoxin in a mice model. Lung tissues were harvested from male Swiss albino mice (n=42) following long term oral exposure to high and low doses of fipronil alone or in combination with endotoxin. The differentially expressed genes were analyzed by Ingenuity pathway analysis software to predict the top canonical pathways. The microarray data for selected genes was validated using quantitative PCR and immunohistochemistry. Results Both BAL fluid and histopathology analysis suggested lung damage and altered transcriptomic profile of lung following exposure to high and low dose of fipronil with or without endotoxin. PCP pathway was among the top upregulated canonical pathways following exposure to both doses of fipronil individually or with LPS. Low dose of fipronil increased the expression of WNT-6, MAPK-8, IL-4 and IL-17C while higher dose decreased the expression of MAPK-8 and IL-17C. The expression data verified by realtime PCR was in concordance with microarray data. Conclusion Long-term exposure to low (4.75 mg kg-1) and high (9.50 mg kg-1) dose of fipronil alone or in combination with endotoxins alters the histoarchitecture and transcriptome profile of lungs with the involvement of the PCP pathway. PCP pathway showed higher enrichment in low dose group of fipronil alone or in combination with LPS. The data from the study provides the insights of the potential damage on lungs caused by fipronil and endotoxin interaction and helps to better understand the mechanism of this complex relation.
Pesticide residues in food and environment along with airborne contaminants such as endotoxins pose health risk. Although herbicide 2,4-Dichlorophenoxyacetic acid (2,4-D) has been associated with ...increased risk of lung cancers such as small cell lung cancer (SCLC) among agricultural workers, there are no data on the SCLC signaling pathway upon 2,4-D exposure without LPS or in combination with endotoxin.
We exposed Swiss albino mice (N = 48) orally to high (9.58 mg kg
) and low (5.12 mg kg
) dosages of 2,4-D dissolved in corn oil for 90 days followed by E. coli lipopolysaccharide (LPS) or normal saline solution (80 μl/animal). Lung samples and broncho-alveolar fluid (BALF) were subjected to Total histological score (THS) and total leucocyte count (TLC) and differential leucocytes count (DLC) analyses, respectively. We used microarray and bioinformatics tools for transcriptomic analyses and differentially expressed genes were analyzed to predict the top canonical pathways followed by validation of selected genes by qRT-PCR and immunohistochemistry.
Total histological score (THS) along with BALF analyses showed lung inflammation following long term dietary exposure to high or low doses of 2,4-D individually or in combination with LPS. Microarray analysis revealed exposure to high dose of 2,4-D without or with LPS upregulated 2178 and 2142 and downregulated 1965 and 1719 genes, respectively (p < 0.05; minimum cut off 1.5 log fold change). The low dose without or with LPS upregulated 2133 and 2054 and downregulated 1838 and 1625 genes, respectively. Bioinformatics analysis showed SCLC as topmost dysregulated pathway along with differential expression of Itgb1, NF-κB1, p53, Cdk6 and Apaf1. Immunohistological and quantitative real time PCR (qRT-PCR) analyses also supported the transcriptomic data.
Taken together, the data show exposures to high and low dose of 2,4-D with/without LPS induced lung inflammation and altered pulmonary transcriptome profile with the involvement of the SCLC pathway. The data from the study provide the insights of the potential damage on lungs caused by 2,4-D and help to better understand the mechanism of this complex relation.
•Exposure to combined LPS and glyphosate generated a differential lung inflammatory response.•Repeated LPS and glyphosate exposure induced inflammation distinguishable from individual ...exposures.•Inflammation attenuated with repeated exposures but persistence inflammatory cells persisted.
Agricultural airborne work exposures are complex in nature and workplace exposures are a risk for respiratory outcomes in workers. Endotoxin and glyphosate are two common agents in agricultural exposures. While endotoxin (lipopolysaccaride, LPS) is a potent inflammatory agent it explains only a portion of the respiratory inflammatory response. The inflammatory potential when LPS is presented with another common agricultural respiratory agent, glyphosate, is not known. Methods: Mice were assigned to four treatment groups: control, LPS alone, glyphosate alone, glyphosate and LPS combined. Treatments were for 1, 5 or 10 days. Results: Five days of repeated exposure to the comintation of LPS and glyphosate resulted in higher neutrophil counts, myloperoxidase, TNF-α, IL-6, KC levels, and ICAM-1 and TLR-2 expression compared to the same length of treatment to LPS or glyphosate alone. After 10-days of exposure, inflammatory responses decreased, however leukocyte infiltration persisted along with increases in IL-4. Conclusions: Glyphosate exposure modified LPS induced lung inflammatory responses and TLR-2 may be important in the modulated inflammatory response.
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