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Project Bibliography

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Leite et al., 2019

Leite, S. B., Franco de Diana, D. M., Segovia Abreu, J. A., Avalos, D. S., Denis, M. A., Ovelar, C. C., Samaniego Royg, M. J., Thielmann Arbo, B. A., & Corvalan, R.; “DNA damage induced by exposure to pesticides in children of rural areas in Paraguay;” Indian Journal of Medical Research, 2019, 150(3), 290-296; DOI: 10.4103/ijmr.IJMR_1497_17.

ABSTRACT:

BACKGROUND & OBJECTIVES:

Chronic exposure to pesticides can damage DNA and lead to cancer, diabetes, respiratory diseases and neurodegenerative and neurodevelopment disorders. The objective of this study was to determine the frequency of DNA damage through the comet assay and micronucleus (MN) test in two groups of children, under 10 yr of age living in rural Paraguay and in relation to pesticide exposure.

METHODS:

Two groups of 5 to 10 yr old children were formed; the exposed group (group A, n=43), born and currently living in a community dedicated to family agriculture and surrounded by transgenic soybean crops, and the control group (group B, n=41), born and living in a community dedicated to family agriculture with biological control of pests. For each child, 2000 cells were studied for the MN test and 200 cells for the comet assay.

RESULTS:

The comparison between exposed and control children revealed significant differences in biomarkers studied for the measurement of genetic damage (cell death and DNA damage). The median of MN was higher in the exposed group (6 vs. 1) (P <0.001). Binucleated cells (2.9 vs. 0.5, P <0.001); broken eggs (5.5 vs. 1.0, P <0.001); karyorrhexis (6.7 vs. 0.5, P <0.001); kariolysis (14.0 vs. 1.0, P <0.001); pyknosis (7.4 vs. 1.2, P <0.001) and condensed chromatin (25.5 vs. 7.0, P <0.001) were significantly higher in the exposed group. The values of tail length (59.1 vs 37.2 mum); tail moment (TM) (32.8 vs. 14.4 mum); TM olive (15.5 vs. 6); % DNA tail (45.2 vs. 27.6) and % DNA head (54.8 vs. 72.4), were significantly different between the two groups.

INTERPRETATIONS & CONCLUSIONS:

In children exposed to pesticides, a greater genotoxic and cytotoxic effect was observed compared to non-exposed children. Our findings suggest that monitoring of genetic toxicity in population exposed to pesticides and agrochemicals should be done.

FULL TEXT


Sherwin et al., 2019

Sherwin, E., Bordenstein, S. R., Quinn, J. L., Dinan, T. G., & Cryan, J. F.; “Microbiota and the social brain;” Science, 2019, 366(6465); DOI: 10.1126/science.aar2016.

ABSTRACT:

Sociability can facilitate mutually beneficial outcomes such as division of labor, cooperative care, and increased immunity, but sociability can also promote negative outcomes, including aggression and coercion. Accumulating evidence suggests that symbiotic microorganisms, specifically the microbiota that reside within the gastrointestinal system, may influence neurodevelopment and programming of social behaviors across diverse animal species. This relationship between host and microbes hints that host-microbiota interactions may have influenced the evolution of social behaviors. Indeed, the gastrointestinal microbiota is used by certain species as a means to facilitate communication among conspecifics. Further understanding of how microbiota influence the brain in nature may be helpful for elucidating the causal mechanisms underlying sociability and for generating new therapeutic strategies for social disorders in humans, such as autism spectrum disorders (ASDs). FULL TEXT


Lajmanovich et al., 2019

Lajmanovich, R. C., Peltzer, P. M., Attademo, A. M., Martinuzzi, C. S., Simoniello, M. F., Colussi, C. L., Cuzziol Boccioni, A. P., & Sigrist, M.; “First evaluation of novel potential synergistic effects of glyphosate and arsenic mixture on Rhinella arenarum (Anura: Bufonidae) tadpoles;” Heliyon, 2019, 5(10), e02601; DOI: 10.1016/j.heliyon.2019.e02601.

ABSTRACT:

The toxicity of glyphosate-based herbicide (GBH) and arsenite (As(III)) as individual toxicants and in mixture (50:50 v/v, GBH-As(III)) was determined in Rhinella arenarum tadpoles during acute (48 h) and chronic assays (22 days). In both types of assays, the levels of enzymatic activity [Acetylcholinesterase (AChE), Carboxylesterase (CbE), and Glutathione S-transferase (GST)] and the levels of thyroid hormones (triiodothyronine; T3 and thyroxine; T4) were examined. Additionally, the mitotic index (MI) of red blood cells (RBCs) and DNA damage index were calculated for the chronic assay. The results showed that the LC50 values at 48 h were 45.95 mg/L for GBH, 37.32 mg/L for As(III), and 30.31 mg/L for GBH-As(III) (with similar NOEC = 10 mg/L and LOEC = 20 mg/L between the three treatments). In the acute assay, Marking’s additive index (S = 2.72) indicated synergistic toxicity for GBH-As(III). In larvae treated with GBH and As(III) at the NOEC-48h (10 mg/L), AChE activity increased by 36.25% and 33.05% respectively, CbE activity increased by 22.25% and 39.05 % respectively, and GST activity increased by 46.75% with the individual treatment with GBH and by 131.65 % with the GBH-As(III) mixture. Larvae exposed to the GBH-As(III) mixture also showed increased levels of T4 (25.67 %). In the chronic assay at NOEC-48h/8 (1.25 mg/L), As(III) and GBH-As(III) inhibited AChE activity (by 39.46 % and 35.65%, respectively), but did not alter CbE activity. In addition, As(III) highly increased (93.7 %) GST activity. GBH-As(III) increased T3 (97.34%) and T4 (540.93%) levels. Finally, GBH-As(III) increased the MI of RBCs and DNA damage. This study demonstrated strong synergistic toxicity of the GBH-As(III) mixture, negatively altering antioxidant systems and thyroid hormone levels, with consequences on RBC proliferation and DNA damage in treated R. arenarum tadpoles. FULL TEXT


Ichikawa et al., 2019

Ichikawa, G., Kuribayashi, R., Ikenaka, Y., Ichise, T., Nakayama, S. M. M., Ishizuka, M., Taira, K., Fujioka, K., Sairenchi, T., Kobashi, G., Bonmatin, J. M., & Yoshihara, S.; “LC-ESI/MS/MS analysis of neonicotinoids in urine of very low birth weight infants at birth;” Plos One, 2019, 14(7), e0219208; DOI: 10.1371/journal.pone.0219208.

ABSTRACT:

OBJECTIVES:

Neonicotinoid insecticides are widely used systemic pesticides with nicotinic acetylcholine receptor agonist activity that are a concern as environmental pollutants. Neonicotinoids in humans and the environment have been widely reported, but few studies have examined their presence in fetuses and newborns. The objective of this study is to determine exposure to neonicotinoids and metabolites in very low birth weight (VLBW) infants.

METHODS:

An analytical method for seven neonicotinoids and one neonicotinoid metabolite, N-desmethylacetamiprid (DMAP), in human urine using LC-ESI/MS/MS was developed. This method was used for analysis of 57 urine samples collected within 48 hours after birth from VLBW infants of gestational age 23-34 weeks (male/female = 36/21, small for gestational age (SGA)/appropriate gestational age (AGA) = 6/51) who were admitted to the neonatal intensive care unit of Dokkyo Hospital from January 2009 to December 2010. Sixty-five samples collected on postnatal day 14 (M/F = 37/22, SGA/AGA = 7/52) were also analyzed.

RESULTS:

DMAP, a metabolite of acetamiprid, was detected in 14 urine samples collected at birth (24.6%, median level 0.048 ppb) and in 7 samples collected on postnatal day 14 (11.9%, median level 0.09 ppb). The urinary DMAP detection rate and level were higher in SGA than in AGA infants (both p<0.05). There were no correlations between the DMAP level and infant physique indexes (length, height, and head circumference SD scores).

CONCLUSION:

These results provide the first evidence worldwide of neonicotinoid exposure in newborn babies in the early phase after birth. The findings suggest a need to examine potential neurodevelopmental toxicity of neonicotinoids and metabolites in human fetuses.

FULL TEXT


Qiu et al., 2020

Qiu, Shengnan, Fu, Huiyang, Zhou, Ruiying, Yang, Zheng, Bai, Guangdong, & Shi, Baoming; “Toxic effects of glyphosate on intestinal morphology, antioxidant capacity and barrier function in weaned piglets;” Ecotoxicology and Environmental Safety, 2020, 187; DOI: 10.1016/j.ecoenv.2019.109846.

ABSTRACT:

At present, the public is paying more attention to the adverse effects of pesticides on human and animal health and the environment. Glyphosate is a broad-spectrum pesticide that is widely used in agricultural production. In this manuscript, the effects of diets containing glyphosate on intestinal morphology, intestinal immune factors, intestinal antioxidant capacity and the mRNA expression associated with the Nrf2 signaling pathway were investigated in weaned piglets. Twenty-eight healthy female hybrid weaned piglets (Duroc × Landrace × Yorkshire) were randomly selected with an average weight of 12.24 ± 0.61 kg. Weaned piglets were randomly assigned into 4 treatment groups and fed a basal diet supplemented with 0, 10, 20, and 40 mg/kg glyphosate for a 35-day feeding trial. We found that glyphosate had no effect on intestinal morphology. In the duodenum, glyphosate increased the activities of CAT and SOD (linear, P < 0.05) and increased the levels of MDA (linear and quadratic, P < 0.05). In the duodenum, glyphosate remarkably increased the relative mRNA expression levels of Nrf2 (linear and quadratic, P < 0.05) and NQO1 (linear and quadratic, P < 0.05) and reduced the relative mRNA expression levels of GPx1, HO-1 and GCLM (linear and quadratic, P < 0.05). In the jejunum, glyphosate remarkably increased the relative mRNA expression levels of Nrf2 (linear and quadratic, P < 0.05) and decreased the relative mRNA expression levels of GCLM (linear and quadratic, P < 0.05). Glyphosate increased the mRNA expression levels of IL-6 in the duodenum (linear and quadratic, P < 0.05) and the mRNA expression levels of IL-6 in the jejunum (linear, P < 0.05). Glyphosate increased the mRNA expression of NF-κB in the jejunum (linear, P = 0.05). Additionally, the results demonstrated that glyphosate linearly decreased the ZO-1 mRNA expression levels in the jejunum and the mRNA expression of claudin-1 in the duodenum (P < 0.05). In the duodenum, glyphosate increased the protein expression levels of Nrf2 (linear, P = 0.025). Overall, glyphosate exposure may result in oxidative stress in the intestines of piglets, which can be alleviated by enhancing the activities of antioxidant enzymes and self-detoxification. FULL TEXT


Daisley et al., 2018

Daisley, B. A., Trinder, M., McDowell, T. W., Collins, S. L., Sumarah, M. W., & Reid, G.; “Microbiota-Mediated Modulation of Organophosphate Insecticide Toxicity by Species-Dependent Interactions with Lactobacilli in a Drosophila melanogaster Insect Model;” Applied and Environmental Microbiology, 2018, 84(9); DOI: 10.1128/AEM.02820-17.

ABSTRACT:

Despite the benefits to the global food supply and agricultural economies, pesticides are believed to pose a threat to the health of both humans and wildlife. Chlorpyrifos (CP), a commonly used organophosphate insecticide, has poor target specificity and causes acute neurotoxicity in a wide range of species via the suppression of acetylcholinesterase. This effect is exacerbated 10- to 100-fold by chlorpyrifos oxon (CPO), a principal metabolite of CP. Since many animal-associated symbiont microorganisms are known to hydrolyze CP into CPO, we used a Drosophila melanogaster insect model to investigate the hypothesis that indigenous and probiotic bacteria could affect CP metabolism and toxicity. Antibiotic-treated and germfree D. melanogaster insects lived significantly longer than their conventionally reared counterparts when exposed to 10 muM CP. Drosophila melanogaster gut-derived Lactobacillus plantarum, but not Acetobacterindonesiensis, was shown to metabolize CP. Liquid chromatography tandem-mass spectrometry confirmed that the L. plantarum isolate preferentially metabolized CP into CPO when grown in CP-spiked culture medium. Further experiments showed that monoassociating germfree D. melanogaster with the L. plantarum isolate could reestablish a conventional-like sensitivity to CP. Interestingly, supplementation with the human probiotic Lactobacillus rhamnosus GG (a strain that binds but does not metabolize CP) significantly increased the survival of the CP-exposed germfree D. melanogaster This suggests strain-specific differences in CP metabolism may exist among lactobacilli and emphasizes the need for further investigation. In summary, these results suggest that (i) CPO formation by the gut microbiota can have biologically relevant consequences for the host, and (ii) probiotic lactobacilli may be beneficial in reducing in vivo CP toxicity.IMPORTANCE An understudied area of research is how the microbiota (microorganisms living in/on an animal) affects the metabolism and toxic outcomes of environmental pollutants such as pesticides. This study focused specifically on how the microbial biotransformation of chlorpyrifos (CP; a common organophosphate insecticide) affected host exposure and toxicity parameters in a Drosophila melanogaster insect model. Our results demonstrate that the biotransformation of CP by the gut microbiota had biologically relevant and toxic consequences on host health and that certain probiotic lactobacilli may be beneficial in reducing CP toxicity. Since inadvertent pesticide exposure is suspected to negatively impact the health of off-target species, these findings may provide useful information for wildlife conservation and environmental sustainability planning. Furthermore, the results highlight the need to consider microbiota composition differences between beneficial and pest insects in future insecticide designs. More broadly, this study supports the use of beneficial microorganisms to modulate the microbiota-mediated biotransformation of xenobiotics. FULL TEXT


Xia et al., 2018

Xia, X., Sun, B., Gurr, G. M., Vasseur, L., Xue, M., & You, M.; “Gut Microbiota Mediate Insecticide Resistance in the Diamondback Moth, Plutella xylostella (L.);” Frontiers in Microbiology, 2018, 9, 25; DOI: 10.3389/fmicb.2018.00025.

ABSTRACT:

The development of insecticide resistance in insect pests is a worldwide concern and elucidating the underlying mechanisms is critical for effective crop protection. Recent studies have indicated potential links between insect gut microbiota and insecticide resistance and these may apply to the diamondback moth, Plutella xylostella (L.), a globally and economically important pest of cruciferous crops. We isolated Enterococcus sp. (Firmicutes), Enterobacter sp. (Proteobacteria), and Serratia sp. (Proteobacteria) from the guts of P. xylostella and analyzed the effects on, and underlying mechanisms of insecticide resistance. Enterococcus sp. enhanced resistance to the widely used insecticide, chlorpyrifos, in P. xylostella, while in contrast, Serratia sp. decreased resistance and Enterobacter sp. and all strains of heat-killed bacteria had no effect. Importantly, the direct degradation of chlorpyrifos in vitro was consistent among the three strains of bacteria. We found that Enterococcus sp., vitamin C, and acetylsalicylic acid enhanced insecticide resistance in P. xylostella and had similar effects on expression of P. xylostella antimicrobial peptides. Expression of cecropin was down-regulated by the two compounds, while gloverin was up-regulated. Bacteria that were not associated with insecticide resistance induced contrasting gene expression profiles to Enterococcus sp. and the compounds. Our studies confirmed that gut bacteria play an important role in P. xylostella insecticide resistance, but the main mechanism is not direct detoxification of insecticides by gut bacteria. We also suggest that the influence of gut bacteria on insecticide resistance may depend on effects on the immune system. Our work advances understanding of the evolution of insecticide resistance in this key pest and highlights directions for research into insecticide resistance in other insect pest species. FULL TEXT


Koppel et al., 2017

Koppel, N., Maini Rekdal, V., & Balskus, E. P.; “Chemical transformation of xenobiotics by the human gut microbiota;” Science, 2017, 356(6344); DOI: 10.1126/science.aag2770.

ABSTRACT:

The human gut microbiota makes key contributions to the metabolism of ingested compounds (xenobiotics), transforming hundreds of dietary components, industrial chemicals, and pharmaceuticals into metabolites with altered activities, toxicities, and lifetimes within the body. The chemistry of gut microbial xenobiotic metabolism is often distinct from that of host enzymes. Despite their important consequences for human biology, the gut microbes, genes, and enzymes involved in xenobiotic metabolism are poorly understood. Linking these microbial transformations to enzymes and elucidating their biological effects is undoubtedly challenging. However, recent studies demonstrate that integrating traditional and emerging technologies can enable progress toward this goal. Ultimately, a molecular understanding of gut microbial xenobiotic metabolism will guide personalized medicine and nutrition, inform toxicology risk assessment, and improve drug discovery and development. FULL TEXT


Larsen et al., 2017

Larsen, A. E., Gaines, S. D., & Deschenes, O.; “Agricultural pesticide use and adverse birth outcomes in the San Joaquin Valley of California;” Nature Communications, 2017, 8(1), 302; DOI: 10.1038/s41467-017-00349-2.

ABSTRACT:

Virtually all agricultural communities worldwide are exposed to agricultural pesticides. Yet, the health consequences of such exposure are poorly understood, and the scientific literature remains ambiguous. Using individual birth and demographic characteristics for over 500 000 birth observations between 1997-2011 in the agriculturally dominated San Joaquin Valley, California, we statistically investigate if residential agricultural pesticide exposure during gestation, by trimester, and by toxicity influences birth weight, gestational length, or birth abnormalities. Overall, our analysis indicates that agricultural pesticide exposure increases adverse birth outcomes by 5-9%, but only among the population exposed to very high quantities of pesticides (e.g., top 5th percentile, i.e., ~4200 kg applied over gestation). Thus, policies and interventions targeting the extreme right tail of the pesticide distribution near human habitation could largely eliminate the adverse birth outcomes associated with agricultural pesticide exposure documented in this study.The health consequences of exposure to pesticides are uncertain and subject to much debate. Here, the effect of exposure during pregnancy is investigated in an agriculturally dominated residential area, showing that an increase in adverse birth outcomes is observed with very high levels of pesticide exposure. FULL TEXT


Mesnage, 2019

Mesnage, Robin, “Effects of dietary exposures to pesticide residues on the gut microbiome,” 2019, Presented 10/30/2019 at the London Microbiome Meeting 2019, Great Hall, King’s College London Strand Campus.

SUMMARY:

The gut microbiota: a major player in the toxicity of environmental pollutants?

FULL TEXT


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