Cited by 208Pesticide Exposure and ToxicityParaquat toxicity studies and treatmentsDrug-Induced Hepatotoxicity and Protection

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Oxidative stress responses of rats exposed to Roundup and its active ingredient glyphosate

El-Shenawy, Nahla S.·2009·Environmental Toxicology and Pharmacology

DOI 10.1016/j.etap.2009.06.001

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Abstract

Glyphosate is the active ingredient and polyoxyethyleneamine, the major component, is the surfactant present in the herbicide Roundup formulation. The objective of this study was to analyze potential cytotoxicity of the Roundup and its fundamental substance (glyphosate). Albino male rats were intraperitoneally treated with sub-lethal concentration of Roundup (269.9mg/kg) or glyphosate (134.95mg/kg) each 2 days, during 2 weeks. Hepatotoxicity was monitored by quantitative analysis of the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) activities, total protein, albumin, triglyceride and cholesterol. Creatinine and urea were used as the biochemical markers of kidney damages. The second aim of this study to investigate how glyphosate alone or included in herbicide Roundup affected hepatic reduced glutathione (GSH) and lipid peroxidation (LPO) levels of animals as an index of antioxidant status and oxidative stress, respectively, as well as the serum nitric oxide (NO) and alpha tumour necrosis factor (TNF-α) were measured. Treatment of animals with Roundup induced the leakage of hepatic intracellular enzymes, ALT, AST and ALP suggesting irreversible damage in hepatocytes starting from the first week. It was found that the effects were different on the enzymes in Roundup and glyphosate-treated groups. Significant time-dependent depletion of GSH levels and induction of oxidative stress in liver by the elevated levels of LPO, further confirmed the potential of Roundup to induce oxidative stress in hepatic tissue. However, glyphosate caused significant increases in NO levels more than Roundup after 2 weeks of treatment. Both treatments increased the level of TNF-α by the same manner. The results suggest that excessive antioxidant disruptor and oxidative stress is induced with Roundup than glyphosate.

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RETRACTED: Safety Evaluation and Risk Assessment of the Herbicide Roundup and Its Active Ingredient, Glyphosate, for Humans
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BackgroundResultInfluential
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Background
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Background
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Background
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Oxidative stress induced by Roundup in rat liver and brain: attenuation by zinc sulfate
Djaber, N., Khelef, Y., Ounaceur, L. S., Moubine, B. N., Rouag, M., Berrouague, S., Amara, H., Taïbi, F., Boumendjel, M., Boumendjel, A., et al. (2022) · Comparative Clinical Pathology · doi:10.1007/s00580-022-03327-3 · Cited by 5
“1 3 The dose of RDP was selected on the basis of a previous study of El-Shenawy (2009), with 1/18 of LD50 (269.9 mg/ kg bw).”
MethodInfluential
Can glyphosate’s disruption of the gut microbiome and induction of sulfate deficiency explain the epidemic in gout and associated diseases in the industrialized world?
Seneff, S., Causton, N. J., Nigh, G., Koenig, G., & Avalon, D. (2017) · Journal of Biological Physics and Chemistry · doi:10.4024/04se17a.jbpc.17.02 · Cited by 5
Influence of the soil organic matter content on voltammetric determination of derivatised glyphosate in herbicide contaminated soils
Daňhel, A., Moreira, J. C., Jacob, S. D. C., & Barek, J. (2011) · Collection of Czechoslovak Chemical Communications · doi:10.1135/cccc2011086 · Cited by 5
Maternal exposure to glyphosate increased the risk of adverse neurodevelopmental outcomes in rodent offspring: A systematic review
Marins, K., Bianco, C. D., da Silva, A. H., & Zamoner, A. (2024) · Environmental Pollution · doi:10.1016/j.envpol.2024.125086 · Cited by 4
Glyphosate and Anencephaly: Death by A Thousand Cuts
Seneff, S. (2017) · Journal of Neurology and Neurobiology · doi:10.16966/2379-7150.140 · Cited by 6
Oxidative Stress: A Potential Link Between Pesticide Exposure and Early-Life Neurological Disorders
Mani, S., Jain, A., Gulati, A., Tyagi, S., Pal, K. V., Jaiswal, H., & Singh, M. (2021) · Molecular and integrative toxicology · doi:10.1007/978-3-030-83446-3_10 · Cited by 3
Influences of Glyphosate Contaminations and Concentrate Feed on Performance, Blood Parameters, Blood Cell Functionality and DNA Damage Properties in Fattening Bulls
Heymann, A.-K., Schnabel, K., Billenkamp, F., Bühler, S., Frahm, J., Kersten, S., Meyer, U., von Soosten, D., & Dänicke, S. (2023) · Animals · doi:10.3390/ani13091499 · Cited by 4
Involvement of glyphosate in disruption of biotransformation P450 enzymes and hepatic lipid metabolism in chicken
Fathi, M. A., Shen, D., Abdelsalam, A. M., & Li, C. (2023) · Animal Biotechnology · doi:10.1080/10495398.2023.2214601 · Cited by 4
“52 As a result, it is crucial to investigate the impact of glyphosate on the levels of immune gene expression, such as cytokines and transcription factor in the chicken liver.”
Background
Protective Effect of Andrographis paniculata Against Atrazine Induced Renotoxicity in Albino Rats
Iosr, P., & Shirisha, K. (2013) · IOSR Journal of Pharmacy (IOSRPHR) · doi:10.6084/m9.figshare.875302.v1 · Cited by 4
“This process, if out of control, can alter essential cell functions and lead to cell death (Kappus 1987) [7].”
Background
Glyphosate-Induced Metabolic and Immune Modulation in Hepatoma Cells: Identification of Key Genes as Diagnostic and Therapeutic Targets Using an In Silico Systems Biology Approach
Mishra, D. (2026) · Journal of Xenobiotics · doi:10.3390/jox16020051 · Cited by 3
“…has been evaluated through alterations in standard liver function tests that include serum alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase activities, along with measurements of serum lipoproteins, albumin, total protein, triglyceride and cholesterol [18,19].”
Protective Role of Adansonia digitata Extract Against Glyphosate-induced Hepatorenal Toxicity in Adult Male Wistar Rats
Ini, A. T., Makena, W., Usman, I. M., Aminu, A., & Gadzama, M. N. (2022) · Iranian Journal of Toxicology · doi:10.32598/ijt.16.2.920.1 · Cited by 3
“This could explain that glyphosate disrupts the liver cell membranes and kidneys glomeruli [21, 22].”
Background
Potential hazards of glyphosate on rabbit retina
Aly, E., Morsy, S. A., Ibrahim, A., Mahmoud, S. S., & Kamal, G. (2017) · Journal of The Arab Society for Medical Research · doi:10.4103/jasmr.jasmr_10_17 · Cited by 3
Acute toxicity of cyprodinil, glyphosate isopropylamine salt, and indoxacarb pesticides in narrow-clawed crayfish, Pontastacus leptodactylus (Eschscholtz, 1823)
Taştan, Y., & Sönmez, A. Y. (2025) · Environmental Toxicology and Chemistry · doi:10.1093/etojnl/vgaf131 · Cited by 2
Urine glyphosate levels and kidney function outcomes in a cohort study of workers in El Salvador and Nicaragua
Rodgers, K. M., Fimbres, J., Amador, J. J., Jarquin, E., García, P., López-Pilarte, D., Keogh, S. A., Petropoulos, Z. E., Reynolds, M., Kannan, K., et al. (2026) · Journal of Exposure Science & Environmental Epidemiology · doi:10.1038/s41370-026-00913-3 · Cited by 2
Chemoprotective Potentials of Selected Dietary Supplements in Glyphosate-based Herbicide-induced Nephrotoxicity and Dyslipidemia in Albino Wistar Rats
Ujowundu, C. O., Eberechukw, A., Ujowundu, F. N., Anna, O. A., Onyemuche Shadrack, O., If, N. A., & Olu, N. M. (2019) · Asian Journal of Biological Sciences · doi:10.3923/ajbs.2019.320.327 · Cited by 2
Glyphosate-induced changes in the expression of galanin and GALR1, GALR2 and GALR3 receptors in the porcine small intestine wall
Palus, K., Chmielewska‐Krzesińska, M., Jana, B., & Całka, J. (2024) · Scientific Reports · doi:10.1038/s41598-024-59581-8 · Cited by 2
“Further studies of rats showed sublethal doses of glyphosate to increase malondialdehyde (MDA) levels in the liver 27 , whereas its long-term administration in low doses results in a higher level of MDA in the brain, plasma, kidneys and liver 28 .”
Background
Dual-Hit: Glyphosate exposure at NOAEL level negatively impacts birth and glia-behavioural measures in heterozygous shank3 mutants
Sakkaki, S., Cresto, N., Chancel, R., Jaulmes, M., Zub, E., Blaquière, M., Sicard, P., Maurice, T., Ellero‐Simatos, S., Gamet‐Payrastre, L., et al. (2023) · Environment International · doi:10.1016/j.envint.2023.108201 · Cited by 2
HEMATOLOGICAL AND BIOCHEMICAL CHANGES INDUCED BY CHLORPYRIFOSE AND GLYPHOSATE IN MALE ALBINO RAT'S AND AMELIORATIVE EFFECT OF VITAMIN C
Salem, M., El-zawahry, E.-Y. I., Rasheid, H. E., & Nabeeh, A. (2018) · Al-Azhar Bulletin of Science · doi:10.21608/absb.2018.33760 · Cited by 2
“Glyphosate herbicides ingestion develops acute kidney injury; the kidney may also be an organ for excretion of glyphosate components (El-Shenawy 2009).”
BackgroundResult
Probiotic Bifidobacterium longum Subsp. longum 51A Protects Mice from Genotoxic and Metabolic Alterations Induced by Subchronic Exposure to a Low-Dose Pesticide Cocktail
Souza, M. M. D., de Almeida, V. M., Cruz, C. S., Rocha, V. D. M., Leocádio, P. C. L., Pires, S. A., Oliveira, M. D. V., Brumate, T., de Paiva, M. J. N., Alvarez-Leite, J. I., et al. (2025) · ACS Omega · doi:10.1021/acsomega.5c04121 · Cited by 1
Multigenerational effects of perinatal glyphosate exposure in rats: Developmental alterations, increased mortality and oxidative imbalance
Almirón, A., Lorenz, V., Attademo, A. M., Demonte, L. D., Repetti, M. R., Durando, M., & Milesi, M. M. (2026) · Environmental Toxicology and Pharmacology · doi:10.1016/j.etap.2026.105065 · Cited by 1
C60 Fullerene Promotes Restoration of Kidney Function After Chronic Glyphosate Intoxication
Abramchuk, O., Nozdrenko, D., Prylutska, S., Pronko, I., Maliuk, M., Vareniuk, І., Cherepanov, V. V., Korzhyk, O., Ritter, U., Prylutskyy, Y., et al. (2026) · Molecules · doi:10.3390/molecules31152697 · Cited by 1
Changes in Hepatic Metabolism of Rattus norvegicus Infected to Angiostrongylus cantonensis (Nematoda) and Exposed to Glyphosate-Based Herbicide
Programa de Pós-Graduação em Biologia Parasitária, I. O. C.-F., Braga, B. V., García, J. S., Laboratório de Biologia e Parasitologia de Mamíferos Silvestres Reservatórios, I. O. C.-F., Simões, R. O., Silva, J. S. P., Castro, L. S., Silva, C. H., Instituto de Ciência e Tecnologia em Biomodelos-FIOCRUZ, R. D. J., Maldonado Júnior, A., et al. (2021) · Annals of Agricultural & Crop Sciences · doi:10.26420/annagriccropsci.2021.1092 · Cited by 1
“It has been shown that the effects of glyphosate-based herbicides on total serum protein levels can vary in rodent models, with or without change depending on the concentration of herbicide used in the trials [53,54].”
Background
EVALUATION OF STRESS OF ENVIRONMENTAL RELEVANT CONCENTRATION OF GLYPHOSATE PESTICIDE ON LAMELLIDENS MARGINALIS
Mundhe, A., & Pandit, S. V. (2022) · Pollution Research · doi:10.53550/pr.2022.v41i03.038 · Cited by 1
Mecanismos envolvidos na excitotoxicidade glutamatérgica induzida pela exposição aguda ou crônica ao Roundup® sobre o hipocampo de ratos imaturos
Cattani, D. (2013) · LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) · Cited by 1
EXPOSURE TO GLYPHOSATE OR ROUNDUP ™ DURING ZEBRAFISH EMBRYOGENESIS DIFFERENTIALLY AFFECTS METABOLISM AND SWIMMING BEHAVIOURSPreprint
Lacroix, R., Ibhazehiebo, K., Kaushik, G., & Kurrasch, D. M. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.10.03.510731 · Cited by 1
“…has been evidenced to disrupt mitochondrial metabolism and provokes oxidative damage, as well as activate oxidative stress and compensatory cellular stress response pathways in rats and fish, respectively (Larsen et al., 2012; Olorunsogo et al., 1979; Webster and Santos, 2015; El-Shenawy, 2009).”
Background
Distribución espacial de la enfermedad renal crónica no especificada según el área cultivada y la temperatura del ambiente en El Salvador
Vandervort, D. R., López, D. L., Orantes, C., & Rodríguez, D. S. (2014) · MEDICC Review
Utilizing Chemoproteomic Platforms to Elucidate Toxicological Mechanisms
Ford, B. (2019) · eScholarship (California Digital Library)
Removal of dissolved glyphosate from waters by adsorption under the influence of metals
Herath, M. G. A. D. (2019) · doi:10.32657/10356/137655
Associação de dados clínicos e laboratoriais de residentes da área rural com exposição crônica ao glifosato
Costa, L. F., Borba, B. G., dos Santos, M. D., Selicani, M. L., Silvério, A. P., Machado, S. C., & Silvério, A. C. P. (2021) · Research Society and Development · doi:10.33448/rsd-v10i1.12214
Estudo experimental dos efeitos da exposição repetida ao glifosato sobre o comportamento de ratos
Rialto, T. C. R. (2019) · doi:10.11606/d.60.2019.tde-20092021-200250
Chemicals: pesticides
Felsot, A. S. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-813724-6.00020-7
Developmental Exposure to a Glyphosate-Based Herbicide Induces Long-Term Impairments in the Melatonin Endocrine System and Oxidative Damage in the Striatum of Adult RatsPreprint
Karlsson, O., Pierozan, P., Cattani, D., Zamoner, A., & Brittebo, E. B. (2022) · SSRN Electronic Journal · doi:10.2139/ssrn.4051430
Therapeutic Suitability of Functional Phyto‐Oils Against Oral and MDR‐Pathogens Through Nanotechnology
Sahoo, A., Swain, S. S., Jena, A. K., & Panda, M. (2022) · Wiley eBooks · doi:10.1002/9781119905059.ch6
Impact de l’exposition au glyphosate sur la neuroplasticité – de la mère à la descendance
Charlier, T. D. (2024) · Cahiers de Nutrition et de Diététique · doi:10.1016/j.cnd.2023.12.006
Additional file 2 of Single-cell transcriptome analysis reveals liver injury induced by glyphosate in mice
Wu, J., Sun, X., Wu, C., Hong, X., Xie, L., Shi, Z., Zhao, L., Du, Q., Xiao, W. L., Sun, J., et al. (2023) · Figshare · doi:10.6084/m9.figshare.22605205
Morphology of the hypopharyngeal gland of the stingless bee Scaptotrigona postica (Apidae: Meliponini) and the effects of pesticides
Sousa, R. G. D. A., & Brito, P. V. D. A. (2024) · Apidologie · doi:10.1007/s13592-024-01118-z
“An alternative explanation for the low levels of protein in the Roundup group is the production of free radicals provoked by glyphosate, the active ingredient in Roundup, that may lead to a decrease in protein synthesis (El-Shenawy 2009).”
AVALIAÇÃO DAS SUBSTÂNCIAS QUÍMICAS PRESENTES NO TRIGO E SEUS EFEITOS NA SAÚDE HUMANA
de Oliveira, M. L. S., Magnavita, A. P. A., Lisboa, C. S., Borges, J. D. O., Lopes, A. C., da Silva, J. A., & Alves, F. Q. (2024) · Revista Foco · doi:10.54751/revistafoco.v17n11-028
Association of glyphosate exposure with kidney function impairment in the adolescents and young adults’ population in the U.S. National Health and Nutrition Examination Survey, 2013 to 2016
Zhu, Y., Hu, Y., Zhou, Q., Ruan, L., Zhou, S., Xia, B., & Wang, F. (2024) · Paediatrics & Child Health · doi:10.1093/pch/pxae111
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Hamdaoui, L., Feki, H. E., Amor, M. B., Oudadesse, H., Atwan, M., Alshammari, A. M., Brahmi, F., Ben‐Nasr, H., Badraoui, R., & Rebaï, T. (2025) · Toxics · doi:10.3390/toxics13090752
“…oxidative stress, increase lipid peroxidation, deplete antioxidant defenses, and trigger inflammatory infiltration in the thyroid gland and other tissues, conditions that are known to impair thyroid follicular function, alter peripheral deiodination, and disturb thyroid hormone transport [3,17,65].”
Neurological alterations in adult female rats developmentally exposed to a glyphosate-based herbicide: Potential role of the immune system
Gallegos, C. E., Bartos, M., Gumilar, F., Jodar, D. N. N., Lencinas, I., Bras, C., García, B. N., Delbés, J. A., Domínguez, S., & Baier, C. J. (2025) · Toxicology · doi:10.1016/j.tox.2025.154279
Additional file 1 of Single-cell transcriptome analysis reveals liver injury induced by glyphosate in mice
Wu, J., Sun, X., Wu, C., Hong, X., Xie, L., Shi, Z., Zhao, L., Du, Q., Xiao, W., Sun, J., et al. (2023) · Figshare · doi:10.6084/m9.figshare.22605202
Associations of urinary glyphosate with sarcopenia and muscle mass: Insights from NHANES
Kang, Z., Huang, J., & Liu, H. (2026) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2026.119679
Naringenin alleviates roundup-induced cytoarchitectural derangement of rat hypothalamic-pituitary-adrenal axis via modulating Sirt1/NF-κB/Nrf2 and p38-MAPK/p53 signaling pathways
Mandour, D. A., Aziz, N. M. A., El‐Shetry, E. S., & Ahmed, A. F. A. (2026) · Tissue and Cell · doi:10.1016/j.tice.2026.103492
Développement d'un procédé de traitement de matrices d'origine viticole polluées par des herbicides par couplage bioaugmentation/phytoremédiation : sélection d'un triplet bactéries - sorbant - plante testé en microcosme
Bois, P. (2010) · theses.fr (ABES) · doi:10.70675/5a7324d6zd05bz4b79zb0d0zaa854d0c7d8d
Détermination des effets potentiels du glyphosate sur le comportement social et sexuel et sur le développement du système neuroendocrinien sous-jacent
Dechartres, J. (2019) · theses.fr (ABES) · doi:10.70675/44a21582z7230z4ec1zbe78za9dddf7e615b
Modulation of P2X7-driven purinergic signaling and NLRP3 inflammasome activation underlies the hepatoprotective effects of coenzyme Q10 against glyphosate-based herbicide exposure
Mutluay, D., Yakut, S., TENEKECİ, G. Y., Akı, R. H., Denk, B., & Kara, A. (2026) · Purinergic Signalling · doi:10.1007/s11302-026-10152-8
“The marked elevations in ALT, AST, and ALP observed following GBH exposure in our study clearly indicate a hepatocellular response consistent with previous reports on glyphosate-based herbicides [9, 38].”
A New Nitroimidazole-Based Drug Attenuates Skeletal Myositis and Overcomes Benznidazole Resistance in Experimental Chagas Disease
Lima, G. D. D. A., Gonçalves-Santos, E., Benedetti, M. D., Silva, T. D., Pinheiro, A., Pelinsari, S. M., dos Reis, L. F. C., Gonçalves, R. V., Caldas, I. S., Franco, L. L., et al. (2026) · ACS Pharmacology & Translational Science · doi:10.1021/acsptsci.6c00179

Authors: El-Shenawy, N. S.
Venue: Environmental Toxicology and Pharmacology
Publisher: Elsevier BV
Published: 2009-11
Volume: 28
Issue: 3
Pages: 379-385
ISSN: 1382-6689 (ISSN-L)
DOI: 10.1016/j.etap.2009.06.001
OpenAlex: W2158634663
Cited by: 207
References: 39
Citations by year: 2026: 16 · 2025: 10 · 2024: 13 · 2023: 16 · 2022: 24 · 2021: 18 · 2020: 18 · 2019: 24 · 2018: 9 · 2017: 12 · 2016: 11 · 2015: 3 · 2014: 16 · 2013: 11 · 2012: 4
FWCI: 2.43
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Environmental Toxicology and Pharmacology (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pesticide Exposure and Toxicity
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Paraquat toxicity studies and treatments
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
Keywords: glyphosate, Roundup, herbicide toxicity, oxidative stress, hepatotoxicity, reduced glutathione, lipid peroxidation, nitric oxide, TNF-α, antioxidant status, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, kidney injury, rats

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Oxidative stress responses of rats exposed to Roundup and its active ingredient glyphosate

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