151 research outputs found
Transcriptome profile analysis reflects rat liver and kidney damage following chronic ultra-low dose Roundup exposure
No full textBACKGROUND: Glyphosate-based herbicides (GBH) are the major pesticides used worldwide. Converging evidence suggests that GBH, such as Roundup, pose a particular health risk to liver and kidneys although low environmentally relevant doses have not been examined. To address this issue, a 2-year study in rats administering 0.1 ppb Roundup (50 ng/L glyphosate equivalent) via drinking water (giving a daily intake of 4 ng/kg bw/day of glyphosate) was conducted. A marked increased incidence of anatomorphological and blood/urine biochemical changes was indicative of liver and kidney structure and functional pathology. In order to confirm these findings we have conducted a transcriptome microarray analysis of the liver and kidneys from these same animals.
RESULTS: The expression of 4224 and 4447 transcript clusters (a group of probes corresponding to a known or putative gene) were found to be altered respectively in liver and kidney (p < 0.01, q < 0.08). Changes in gene expression varied from -3.5 to 3.7 fold in liver and from -4.3 to 5.3 in kidneys. Among the 1319 transcript clusters whose expression was altered in both tissues, ontological enrichment in 3 functional categories among 868 genes were found. First, genes involved in mRNA splicing and small nucleolar RNA were mostly upregulated, suggesting disruption of normal spliceosome activity. Electron microscopic analysis of hepatocytes confirmed nucleolar structural disruption. Second, genes controlling chromatin structure (especially histone-lysine N-methyltransferases) were mostly upregulated. Third, genes related to respiratory chain complex I and the tricarboxylic acid cycle were mostly downregulated. Pathway analysis suggests a modulation of the mTOR and phosphatidylinositol signalling pathways. Gene disturbances associated with the chronic administration of ultra-low dose Roundup reflect a liver and kidney lipotoxic condition and increased cellular growth that may be linked with regeneration in response to toxic effects causing damage to tissues. Observed alterations in gene expression were consistent with fibrosis, necrosis, phospholipidosis, mitochondrial membrane dysfunction and ischemia, which correlate with and thus confirm observations of pathology made at an anatomical, histological and biochemical level.
CONCLUSION: Our results suggest that chronic exposure to a GBH in an established laboratory animal toxicity model system at an ultra-low, environmental dose can result in liver and kidney damage with potential significant health implications for animal and human populations
Toxicity of Pesticides on Health and Environment
No full textPublic policy is regularly shaken by health crises or unexpected discoveries; future directions in toxicology assessment are therefore urgently needed. Convergent evidences suggest endocrine or nervous disrupting effects of pesticides, as well as effects on wildlife and the environment. These effects are amplified by the use of surfactants and/or combinations of different active principles. The usual concepts of regulatory toxicology are challenged by endocrine, nervous or immune disruption, or epigenetic effects. Indeed, most pollutants alter cell-cell communication systems to promote chronic diseases. They may accumulate in the food chain. Mixtures effects with other pollutants may change their bioavailability and their toxicity. The lack of scientific knowledge in these matters has large costs for public health. This Research Topic focuses on the toxic effects of pesticides associated with large scale cultivation of genetically modified (GM) plants
Long-term fasting improves lipoprotein-associated atherogenic risk in humans
No full textPurpose
Dyslipidemia is a major health concern associated with an increased risk of cardiovascular mortality. Long-term fasting (LF) has been shown to improve plasma lipid profile. We performed an in-depth investigation of lipoprotein composition.
Methods
This observational study included 40 volunteers (50% men, aged 32–65 years), who underwent a medically supervised fast of 14 days (250 kcal/day). Changes in lipid and lipoprotein levels, as well as in lipoprotein subclasses and particles, were measured by ultracentrifugation and nuclear magnetic resonance (NMR) at baseline, and after 7 and 14 fasting days.
Results
The largest changes were found after 14 fasting days. There were significant reductions in triglycerides (TG, − 0.35 ± 0.1 mmol/L), very low-density lipoprotein (VLDL)-TG (− 0.46 ± 0.08 mmol/L), VLDL-cholesterol (VLDL-C, − 0.16 ± 0.03 mmol/L) and low-density lipoprotein (LDL)-C (− 0.72 ± 0.14 mmol/L). Analysis of LDL subclasses showed a significant decrease in LDL1-C (− 0.16 ± 0.05 mmol/L), LDL2-C (− 0.30 ± 0.06 mmol/L) and LDL3-C (− 0.27 ± 0.05 mmol/L). NMR spectroscopy showed a significant reduction in large VLDL particles (− 5.18 ± 1.26 nmol/L), as well as large (− 244.13 ± 39.45 nmol/L) and small LDL particles (− 38.45 ± 44.04 nmol/L). A significant decrease in high-density lipoprotein (HDL)-C (− 0.16 ± 0.04 mmol/L) was observed. By contrast, the concentration in large HDL particles was significantly raised. Apolipoprotein A1 decreased significantly whereas apolipoprotein B, lipoprotein(a), fibrinogen and high-sensitivity C-reactive protein were unchanged.
Conclusion
Our results suggest that LF improves lipoprotein levels and lipoprotein subclasses and ameliorates the lipoprotein-associated atherogenic risk profile, suggesting a reduction in the cardiovascular risk linked to dyslipidemia
Republished study: long-term toxicity of a Roundup herbicide and a Roundup-tolerantgenetically modified maize
No full textThe health effects of a Roundup-tolerant NK603 genetically modified (GM) maize (from 11% in the diet), cultivated with or without Roundup application and Roundup alone (from 0.1 ppb of the full pesticide containing glyphosate and adjuvants) in drinking water, were evaluated for 2 years in rats. This study constitutes a follow-up investigation of a 90-day feeding study conducted by Monsanto in order to obtain commercial release of this GMO, employing the same rat strain and analyzing biochemical parameters on the same number of animals per group as our investigation. Our research represents the first chronic study on these substances, in which all observations including tumors are reported chronologically. Thus, it was not designed as a carcinogenicity study. We report the major findings with 34 organs observed and 56 parameters analyzed at 11 time points for most organs
Co-formulants in glyphosate-based herbicides disrupt aromatase activity in human cells below toxic levels
No full textPesticide formulations contain declared active ingredients and co-formulants presented as inert and confidential compounds. We tested the endocrine disruption of co-formulants in six glyphosate-based herbicides (GBH), the most used pesticides worldwide. All co-formulants and formulations were comparably cytotoxic well below the agricultural dilution of 1% (18-2000 times for co-formulants, 8-141 times for formulations), and not the declared active ingredient glyphosate (G) alone. The endocrine-disrupting effects of all these compounds were measured on aromatase activity, a key enzyme in the balance of sex hormones, below the toxicity threshold. Aromatase activity was decreased both by the co-formulants alone (polyethoxylated tallow amine—POEA and alkyl polyglucoside—APG) and by the formulations, from concentrations 800 times lower than the agricultural dilutions; while G exerted an effect only at 1/3 of the agricultural dilution. It was demonstrated for the first time that endocrine disruption by GBH could not only be due to the declared active ingredient but also to co-formulants. These results could explain numerous in vivo results with GBHs not seen with G alone; moreover, they challenge the relevance of the acceptable daily intake (ADI) value for GBHs exposures, currently calculated from toxicity tests of the declared active ingredient alone.Fil: Defarge, Nicolas. Universite de Caen Basse Normandie; Francia. CRIIGEN; FranciaFil: Takács, Eszter. National Agricultural Research and Innovation Centre; HungríaFil: Lozano, Verónica Laura. Universite de Caen Basse Normandie; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Mesnage, Robin. Universite de Caen Basse Normandie; Francia. CRIIGEN; FranciaFil: de Vendômois, Joël Spiroux. CRIIGEN; FranciaFil: Séralini, Gilles Eric. Universite de Caen Basse Normandie; Francia. CRIIGEN; FranciaFil: Székács, András. National Agricultural Research and Innovation Centre; Hungrí
Long-term fasting induces a remodelling of fatty acid composition in erythrocyte membranes
No full textIntroduction: Long-term fasting (LF) activates an adaptative response to switch metabolic fuels from food glucose to lipids stored in adipose tissues. The increase in free fatty acid (FFA) oxidation during fasting triggers health benefits. We questioned if the changes in lipid metabolism during LF could affect lipids in cell membranes in humans. We thus analysed the FA composition in erythrocyte membranes (EM) during 12.6 ± 3.5 days of LF and 1 month after food reintroduction. Methods: A total of 98 subjects out of three single-arm interventional studies underwent a medical supervised long-term fasting (12.6 ± 3.5 days) programme. The distribution pattern of 26 FA as well as the HS-Omega-3 Index were assessed in the EM using gas chromatography. Results: Eighteen of 26 FA showed significant changes. Within the group of saturated FA, myristic (14:0) and stearic acid (18:0) decreased while palmitic (16:0) and arachid acid (20:0) increased. While most monounsaturated FA increased, trans fatty acids decreased or remained unchanged. Within the polyunsaturated FA, arachidonic (20:4n6) and docosahexaenoic (22:6n3) acid increased, while linoleic (18:2n6), alpha-linolenic (18:3n3) and eicosapentaenoic acid (20:5n3) decreased. Consequently, the HS-Omega-3 Index increased. 11 out of the 18 FA with significant changes returned to baseline levels 1 month afterwards. Levels of linoleic and alpha-linolenic acid increased over baseline levels. Conclusions: Long-term fasting triggers changes in the FA composition of EM
Environmental Health Is Overlooked in Longevity Research
No full textAging is a multifactorial process influenced by genetic predisposition and lifestyle choices. Environmental exposures are too often overlooked. Environmental pollutants—ranging from airborne particulate matter and heavy metals to endocrine disruptors and microplastics—accelerate biological aging. Oxidative stress is a major molecular initiating event, driving inflammation and toxicity across biological levels. We detail the mechanisms by which pollutants enhance reactive oxygen species (ROS) production. This oxidative stress inflicts damage on DNA, proteins, and lipids, accelerating telomere shortening, dysregulating autophagy, and ultimately driving epigenetic age acceleration. For instance, exposure to polycyclic aromatic hydrocarbons, benzene, and pesticides has been associated with increased DNA methylation age. Early-life exposures and lifestyle factors such as tobacco and alcohol consumption further contribute to accelerated biological aging. The cumulative loss of healthy life years caused by these factors can conceivably reach between 5 and 10 years per person. Addressing pollutant-induced accelerated aging through regulatory measures, lifestyle changes, and therapeutic interventions is essential to mitigate their detrimental impacts, ultimately extending healthspan and improving quality of life in aging populations
Reproducibility Analysis of Wood et al., 2023
No full textThis repository contains the analytical code and output for the analyses reported in Guo et al., 2025.
Such analyses pertain to the reproducibility and verification of Table 2 and Figure 2 of the article:
Wood, Eleanor, Sabine Hein, Robin Mesnage, Filipe Fernandes, Nimaya Abhayaratne, Yifan Xu, Zicheng Zhang, Lynne Bell, Claire Williams, and Ana Rodriguez-Mateos. 2023. “Wild Blueberry (Poly) Phenols Can Improve Vascular Function and Cognitive Performance in Healthy Older Individuals: A Double-Blind Randomized Controlled Trial.” The American Journal of Clinical Nutrition 117 (6): 1306–19. https://pubmed.ncbi.nlm.nih.gov/36972800/
Mammalian toxicity of herbicides used in intensive GM crop farming
No full textThe toxicity of major herbicides on mammalian physiology is reviewed, with a focus on herbicides associated with agricultural systems employing genetically modified crops: glyphosate, 2, 4-D, dicamba, glufosinate, quizalofop, sulfonylurea, imidazolinones, mesotrione, and isoxaflutole. Other products used in intensive agriculture worldwide are discussed: paraquat, atrazine, metolachlor, acetochlor, and alachlor. The frequent withdrawal of toxic ingredients creates the impression that herbicides are increasingly safe, but also implies that their initial assessment was insufficient. We highlight knowledge and technical gaps in the determination of safety thresholds: long-term effects of herbicides and their combinations at environmental levels (i.e., real-life exposure scenarios), epigenetics effects, and impacts on the gut microbiome are insufficiently tested. Most of the studies are focused on a few usual suspects (glyphosate, 2, 4-D, atrazine), and the toxicology of some major herbicides remains underexplored. This amplifies the inescapable gap between the introduction of a new herbicide and the detection of its health effects.</p
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