Bibliography Tag: oxidative stress

Eaton et al., 2022

Eaton JL, Cathey AL, Fernandez JA, Watkins DJ, Silver MK, Milne GL, Velez-Vega C, Rosario Z, Cordero J, Alshawabkeh A, Meeker JD; “The association between urinary glyphosate and aminomethyl phosphonic acid with biomarkers of oxidative stress among pregnant women in the PROTECT birth cohort study;” Ecotoxicology and Environmental Safety, 2022, 233:113300; DOI: 10.1016/j.ecoenv.2022.113300.

Background: Glyphosate is a widely used herbicide in global agriculture. Glyphosate and its primary environmental degradate, aminomethyl phosphonic acid (AMPA), have been shown to disrupt endocrine function and induce oxidative stress in in vitro and animal studies. To our knowledge, these relationships have not been previously characterized in epidemiological settings. Elevated urinary levels of glyphosate and AMPA may be indicative of health effects caused by previous exposure via multiple mechanisms including oxidative stress.

Methods: Glyphosate and AMPA were measured in 347 urine samples collected between 16 and 20 weeks gestation and 24-28 weeks gestation from pregnant women in the PROTECT birth cohort. Urinary biomarkers of oxidative stress, comprising 8-isoprostane-prostaglandin-F2α (8-iso-PGF2α), its metabolite 2,3-dinor-5,6-dihydro-15-F2 t-isoprostane (8-isoprostane metabolite) and prostaglandin-F2α (PGF2α), were also measured. Linear mixed effect models assessed the association between exposures and oxidative stress adjusting for maternal age, smoking status, alcohol consumption, household income and specific gravity. Potential nonlinear trends were also assessed using tertiles of glyphosate and AMPA exposure levels.

Results: No significant differences in exposure or oxidative stress biomarker concentrations were observed between study visits. An interquartile range (IQR) increase in AMPA was associated with 9.5% (95% CI: 0.5-19.3%) higher 8-iso-PGF2α metabolite concentrations. Significant linear trends were also identified when examining tertiles of exposure variables. Compared to the lowest exposure group, the second and third tertiles of AMPA were significantly associated with 12.8% (0.6-26.5%) and 15.2% (1.8-30.3%) higher 8-isoprostane metabolite, respectively. An IQR increase in glyphosate was suggestively associated with 4.7% (-0.9 to 10.7%) higher 8-iso-PGF2α.

Conclusions: Urinary concentrations of the main environmental degradate of glyphosate, AMPA, were associated with higher levels of certain oxidative stress biomarkers. Associations with glyphosate reflected similar trends, although findings were not as strong. Additional research is required to better characterize the association between glyphosate exposure and biomarkers of oxidative stress, as well as potential downstream health consequences.


Lopez-Yañez Blanco et al., 2022

Lopez-Yañez Blanco A, Díaz-López KM, Vilchis-Gil J, Diaz-Garcia H, Gomez-Lopez J, Medina-Bravo P, Granados-Riveron JT, Gallardo JM, Klünder-Klünder M, Sánchez-Urbina R.; “Diet and Maternal Obesity Are Associated with Increased Oxidative Stress in Newborns: A Cross-Sectional Study.” Nutrients, 2022; 14(4):746; DOI:10.3390/nu14040746.


Overweight and obesity have become a world-health public problem, mainly for developing countries. Both health conditions have a higher prevalence among women of childbearing age. Physiopathology, overweight and obesity are characterized by a chronic oxidative stress status, which has deleterious effects on mothers and children. Hence, we determine whether the qualities of diet during pregnancy and maternal pregestational body mass index (BMI) are associated with increased oxidative stress markers in mothers and newborns. Two hundred forty-two (242) mother-newborn pairs were classified according to their pregestational BMI. Information on food intake was collected using a food frequency questionnaire in the third trimester of pregnancy. Levels of Malondialdehyde (MDA) and Nitric Oxide (NO) were measured in plasma from mothers at the end of the third trimester of pregnancy and from cord blood at birth. MDA and NO levels in mother–newborn pairs with maternal pregestational overweight or obesity were higher than in mother–newborn pairs with pregestational normal weight. For women (and newborns) who had a higher intake of fruit and vegetables, the levels of NO and MDA were lower. Lastly, women with pregestational obesity had lower fruit and vegetable intake during pregnancy and higher levels of oxidative stress and in their newborns. FULL TEXT

Mesnage et al., 2021D

Robin Mesnage, Mariam Ibragim, Daniele Mandrioli, Laura Falcioni, Eva Tibaldi, Fiorella Belpoggi, Inger Brandsma, Emma Bourne, Emanuel Savage, Charles A Mein, Michael N Antoniou; “Comparative Toxicogenomics of Glyphosate and Roundup Herbicides by Mammalian Stem Cell-Based Genotoxicity Assays and Molecular Profiling in Sprague-Dawley Rats”, Toxicological Sciences, 2021; DOI: 10.1093/toxsci/kfab143.


Whether glyphosate-based herbicides (GBHs) are more potent than glyphosate alone at activating cellular mechanisms, which drive carcinogenesis remain controversial. As GBHs are more cytotoxic than glyphosate, we reasoned they may also be more capable of activating carcinogenic pathways. We tested this hypothesis by comparing the effects of glyphosate with Roundup GBHs both in vitro and in vivo. First, glyphosate was compared with representative GBHs, namely MON 52276 (European Union), MON 76473 (United Kingdom), and MON 76207 (United States) using the mammalian stem cell-based ToxTracker system. Here, MON 52276 and MON 76473, but not glyphosate and MON 76207, activated oxidative stress and unfolded protein responses. Second, molecular profiling of liver was performed in female Sprague-Dawley rats exposed to glyphosate or MON 52276 (at 0.5, 50, and 175 mg/kg bw/day glyphosate) for 90 days. MON 52276 but not glyphosate increased hepatic steatosis and necrosis. MON 52276 and glyphosate altered the expression of genes in liver reflecting TP53 activation by DNA damage and circadian rhythm regulation. Genes most affected in liver were similarly altered in kidneys. Small RNA profiling in liver showed decreased amounts of miR-22 and miR-17 from MON 52276 ingestion. Glyphosate decreased miR-30, whereas miR-10 levels were increased. DNA methylation profiling of liver revealed 5727 and 4496 differentially methylated CpG sites between the control and glyphosate and MON 52276 exposed animals, respectively. Apurinic/apyrimidinic DNA damage formation in liver was increased with glyphosate exposure. Altogether, our results show that Roundup formulations cause more biological changes linked with carcinogenesis than glyphosate. FULL TEXT

Ledda et al., 2021

Ledda C, Cannizzaro E, Cinà D, Filetti V, Vitale E, Paravizzini G, Di Naso C, Iavicoli I, Rapisarda V. “Oxidative stress and DNA damage in agricultural workers after exposure to pesticides.” Journal of Occupational Medicine and Toxicology. 2021 Jan 7;16(1):1. DOI: 10.1186/s12995-020-00290-z.


BACKGROUND: Recent epidemiological studies on workers describe that exposure to pesticides can induce oxidative stress by increased production of free radicals that can accumulate in the cell and damage biological macromolecules, for example, RNA, DNA, DNA repair proteins and other proteins and/or modify antioxidant defense mechanisms, as well as detoxification and scavenger enzymes. This study aimed to assess oxidative stress and DNA damage among workers exposed to pesticides.

METHODS: For this purpose, 52 pesticide exposed workers and 52 organic farmers were enrolled. They were assessed: the pesticide exposure, thiobarbituric acid reactive substances (TBARS), total glutathione (TG), oxidized glutathione levels (GSSG), and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG), levels.

RESULTS: Correlation between pesticide exposure was positively associated with high TBARS and 8-oxodG levels (p < 0.001). A negative association was founded with TG and GSSG and pesticide exposure.

CONCLUSIONS: The present investigation results seem to indicate a mild augment in oxidative stress associated with pesticide exposure, followed by an adaptive response to increase the antioxidant defenses to prevent sustained oxidative adverse effects stress. FULL TEXT

Lee et al., 2017

Lee KM, Park SY, Lee K, Oh SS, Ko SB. “Pesticide metabolite and oxidative stress in male farmers exposed to pesticide.” Annals of Occupational and Environmental Medicine. 2017 Feb 28;29:5, DOI: 10.1186/s40557-017-0162-3.


BACKGROUND: The objective of this study was to measure malondialdehyde (MDA) and isoprostane which has been used as an index of lipid injury, 8-hydroxy-2′-deoxyguanosine (8-OHdG), which has been used as an index of DNA damage, and dialkyl-phosphate (DAP), which has been used to quantify pesticide exposure, and to investigate the relationship between pesticide exposure and oxidative stress.

METHODS: This study was a cross-sectional study that evaluated 84 male farmers exposure to pesticide. In this study, 8-OHdG, isoprostane, and MDA were measured as oxidative stress indices, and dialkyl-phosphate (dimethylphosphate(DMP), diethylphosphate(DEP), dimethylthiophosphate(DMTP), and diethylthiophosphate (DETP)) excreted in the urine was also measured to evaluate pesticide exposure. A linear regression analysis was performed to investigate the relationship between pesticide metabolites, and oxidative stress biomarkers.

RESULTS: A Correlation analysis was performed for pesticide exposure month (PEI), cumulative exposure index (CEI), and DAP as well as the concentration of the oxidative stress biomarkers. The PEM significantly and positively correlated to the levels of 8-OHdG, isoprostane, CEI, and DMP. CEI showed a correlation to 8-OHdG and PEM. DMP, DEP, and DETP showed a positive correlation to 8-OHdG, isoprostane, and MDA. A correlation analysis was adjusted some demographic characteristics, such as age, smoking, drinking, and exercise to determine the relationship between pesticide exposure and oxidative stress. The 8-OHdG, isoprostane, and MDA levels were significantly related to the DMP (ß = 0.320), DEP (ß = 0.390), and DETP (ß = 0.082); DMP (ß = 0.396), DEP (ß = 0.508), and DETP (ß = 0.504); and DMP (ß = 0.432), DEP (ß = 0.508), and DETP (ß = 0.329) levels, respectively.

CONCLUSIONS: The concentration between oxidative stress biomarkers and the pesticide metabolite were a positive correlation. Indicators of oxidative stress was associated with a pesticide metabolite DMP, DEP, and DETP. Therefore, Pesticide exposure and oxidative stress were relevant. FULL TEXT

Ndonwi et al., 2019

Ndonwi EN, Atogho-Tiedeu B, Lontchi-Yimagou E, Shinkafi TS, Nanfa D, Balti EV, Indusmita R, Mahmood A, Katte JC, Mbanya A, Matsha T, Mbanya JC, Shakir A, Sobngwi E. “Gestational Exposure to Pesticides Induces Oxidative Stress and Lipid Peroxidation in Offspring that Persist at Adult Age in an Animal Model.” Toxicological Research, 2019 Jul;35(3):241-248; DOI: 10.5487/TR.2019.35.3.241.


Pesticide exposure may induce biochemical alterations including oxidative stress and lipid peroxidation. However, in the context of developmental origin of health and disease, putative trans-generational effect of exposure to pesticides are insufficiently studied. We therefore aimed to evaluate the biochemical effect of gestational exposure to four pesticides on female Wistar rats and their offspring at adult age. We studied 30 female nulliparous Wistar rats divided into 5 equal groups. Group 1 served as the control group and received distilled water while group 2, 3, 4 and 5 received orally pesticide 1 (imidacloprid), pesticide 2 (chlorpyrifos), pesticide 3 (imidacloprid + lambda cyhalothrin) and pesticide 4 (oxamyl) respectively once daily throughout gestation at a dose equivalent to 1/10 lethal dose 50. The mothers were followed up until one month post gestation. The offspring were followed up from birth until adult age (12 weeks). In all animals at each time point we evaluated malondialdehyde (MDA), oxidative stress and liver function enzymes. There was similar variation of total body weight in all the groups during and after gestation. However, Female Wistar rats of the exposed groups had significant alterations in liver SOD (-30.8% to +64.1%), catalase (-38.8% to -85.7%) and GSH (-29.2% to -86.5%) and; kidney catalase (> 100%), GSH (> 100%). Moreover, MDA, alanine transaminase (ALT) and aspartate transaminase (AST) levels were significantly higher in pesticide exposed rats compared to the control group. Similar alterations in antioxidant enzymes, MDA and liver function enzymes were observed in offspring of treated rats evidenced at weaning and persisting until adult age. Exposure to pesticides causes oxidative stress and lipid peroxidation in exposed female Wistar rats and their offspring. The persistence in offspring at adult age suggests transgenerational adverse effects. FULL TEXT

Coullery et al., 2020

Coullery, R., Pacchioni, A. M., & Rosso, S. B.; “Exposure to glyphosate during pregnancy induces neurobehavioral alterations and downregulation of Wnt5a-CaMKII pathway;” Reproductive Toxicology, 2020, 96, 390-398; DOI: 10.1016/j.reprotox.2020.08.006.


Glyphosate-based formulations are the most popular herbicide used around the world. These herbicides are widely applied in agriculture to control weeds on genetically modified crops. Although there is much evidence showing that glyphosate-based herbicides induce toxic effect on reproductive and hepatic systems, and also cause oxidative damage on cells, studies from recent years revealed that the nervous system may represent a key target for their toxicity. In the present work, we evaluated the effect of glyphosate (without adjuvants) in neonate rats after gestational exposure. Particularly, we examined whether glyphosate during gestation affected the nervous system function at early development. Pregnant Wistar rats were treated with 24 or 35mg/kg of pure glyphosate every 48h and neurobehavioral studies were performed. Our results indicated that gestational exposure to glyphosate induced changes in reflexes development, motor activity and cognitive function, in a dose-dependent manner. To go further, we evaluated whether prenatal exposure to glyphosate affected the Ca(+2)-mediated Wnt non-canonical signaling pathway. Results indicated that embryos exposed to glyphosate showed an inhibition of Wnt5a-CaMKII signaling pathway, an essential cascade controlling the formation and integration of neural circuits. Taken together, these findings suggest that gestational exposure to glyphosate leads to a downregulation of Wnt/Ca(+2) pathway that could induce a developmental neurotoxicity evidenced by deficits at behavioral and cognitive levels in rat pups. FULL TEXT

Mesnage et al., 2021B

Mesnage, R., Teixeira, M., Mandrioli, D., Falcioni, L., Ibragim, M., Ducarmon, Q. R., Zwittink, R. D., Amiel, C., Panoff, J. M., Bourne, E., Savage, E., Mein, C. A., Belpoggi, F., & Antoniou, M. N.; “Multi-omics phenotyping of the gut-liver axis reveals metabolic perturbations from a low-dose pesticide mixture in rats;” Communications Biology, 2021, 4(1), 471; DOI: 10.1038/s42003-021-01990-w.


Health effects of pesticides are not always accurately detected using the current battery of regulatory toxicity tests. We compared standard histopathology and serum biochemistry measures and multi-omics analyses in a subchronic toxicity test of a mixture of six pesticides frequently detected in foodstuffs (azoxystrobin, boscalid, chlorpyrifos, glyphosate, imidacloprid and thiabendazole) in Sprague-Dawley rats. Analysis of water and feed consumption, body weight, histopathology and serum biochemistry showed little effect. Contrastingly, serum and caecum metabolomics revealed that nicotinamide and tryptophan metabolism were affected, which suggested activation of an oxidative stress response. This was not reflected by gut microbial community composition changes evaluated by shotgun metagenomics. Transcriptomics of the liver showed that 257 genes had their expression changed. Gene functions affected included the regulation of response to steroid hormones and the activation of stress response pathways. Genome-wide DNA methylation analysis of the same liver samples showed that 4,255 CpG sites were differentially methylated. Overall, we demonstrated that in-depth molecular profiling in laboratory animals exposed to low concentrations of pesticides allows the detection of metabolic perturbations that would remain undetected by standard regulatory biochemical measures and which could thus improve the predictability of health risks from exposure to chemical pollutants. FULL TEXT

Tang et al., 2021

Tang, J., Wang, W., Jiang, Y., & Chu, W.; “Diazinon exposure produces histological damage, oxidative stress, immune disorders and gut microbiota dysbiosis in crucian carp (Carassius auratus gibelio);” Environmental Pollution, 2021, 269, 116129; DOI: 10.1016/j.envpol.2020.116129.


Diazinon is a common organophosphate pesticide widely used to control parasitic infections in agriculture. Excessive use of diazinon can have adverse effects on the environment and aquatic animal health. In the present study, the toxic effects of diazinon on the histology, antioxidant, innate immune and intestinal microbiota community composition of crucian carp (Carassius auratus gibelio) were investigated. The results showed that diazinon at the tested concentration (300 mug/L) induced gill and liver histopathological damages. Hepatic total superoxide dismutase (T-SOD), catalase (CAT), and glutathione S-transferase (GST) activities significantly decreased (P < 0.05) by 32.47%, 65.33% and 37.34%, respectively. However, the liver tissue malondialdehyde (MDA) content significantly (P < 0.05) increased by 138.83%. The 300 mug/L diazinon significantly (P < 0.05) downregulated the gene expression of TLR4, MyD88, NF-kB p100 and IL-8 but had no significant effect TNF-alpha (P = 0.8239). In addition, the results demonstrated that diazinon exposure could affect the intestinal microbiota composition and diversity. Taken together, the results of this study indicated that diazinon exposure can cause damage to crucian carp, induce histopathological damage in gill and liver tissues, oxidative stress in the liver, and innate immune disorders and alter intestinal microbiota composition and diversity.

Abdel-Halim and Osman, 2020

Abdel-Halim, K. Y., & Osman, S. R.; “Cytotoxicity and Oxidative Stress Responses of Imidacloprid and Glyphosate in Human Prostate Epithelial WPM-Y.1 Cell Line;” Journal of Toxicology, 2020, 2020, 4364650; DOI: 10.1155/2020/4364650.


Insecticide imidacloprid and herbicide glyphosate have a broad spectrum of applicable use in the agricultural sector of Egypt. Their ability to induce in vitro cytotoxic and oxidative stress on normal human cells (prostate epithelial WPM-Y.1 cell line) was evaluated with the methyl tetrazolium test (MTT) and histopathological investigation. Cell viability was evaluated with an MTT test for 24 h. The median inhibition concentration (IC50) values were 0.023 and 0.025 mM for imidacloprid and glyphosate, respectively. Sublethal concentrations: 1/10 and 1/50 of IC50 and IC50 levels significantly induced an increase in the lactate dehydrogenase (LDH) activity and malondialdehyde (MDA) level compared with the untreated cells. Rapid decrease in the glutathione (GSH) content and glutathione-S-transferase (GST) activity was induced. Significant increases were recorded in activities of catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR), respectively, compared with the control group. Transmission electron microscopic (TEM) investigation showed significant defects in the cells following pesticide treatments for 24 h. Therefore, it is concluded that imidacloprid and glyphosate are very toxic in vitro assays and able to induce apoptotic effects as well as oxidative stress. So, these findings provide a scenario of multibiomarkers to achieve the imposed risks of pesticides at low doses. FULL TEXT