Hepatic and Renal Histopathological Changes and Oxidant-Sensitive Fluorescence After 28-Day Glyphosate Exposure in Mice Glyphosate-Induced Hepatic and Renal Injury
International Journal of Medical Toxicology and Forensic Medicine,
Vol. 16 (2026),
1 January 2026
,
Page 1-7
https://doi.org/10.22037/ijmtfm.v16.53790
Abstract
Background: Repeated glyphosate exposure may affect hepatic and renal tissue integrity and redox homeostasis. This study evaluated histopathological changes and oxidant-sensitive fluorescence after a defined 28-day exposure in mice.
Methods: Twenty-four male Swiss albino mice received glyphosate by oral gavage at 50 mg/kg daily for 28 days or saline (n=12/group). We assessed liver and kidney sections for necrosis and inflammation using a semi-quantitative 0–3 scale. Dichlorofluorescein diacetate (DCFH-DA) probe oxidation was measured in tissue homogenates and normalized to protein. Histopathological scores were summarized descriptively; continuous fluorescence outcomes were evaluated using exploratory summary-data Welch comparisons with Holm adjustment.
Results: Mean liver and kidney inflammation scores were 2.0±0.6 and 1.8±0.5 in exposed mice, compared with 0.5±0.3 and 0.5±0.2 in controls. Corresponding necrosis scores were 1.5±0.5 and 1.3±0.4, whereas controls showed none. Liver fluorescence was 2.0±0.5 versus 0.0±0.1 units/mg protein, and kidney fluorescence was 1.8±0.6 versus 0.0±0.1. Mean differences were 2.00 (95% confidence interval [CI], 1.68–2.32) and 1.80 (95% CI, 1.42–2.18), respectively; both Holm-adjusted P values were <0.001.
Conclusion: Under the tested conditions, 28-day glyphosate exposure was associated with hepatic and renal histopathological injury and increased DCFH-DA probe oxidation. The concurrent findings are consistent with altered tissue redox activity but do not identify a specific reactive oxygen species or establish a causal mechanism.
- Alveolar Bone, Fish Oil, Mackerel, Osteoblast, Osteoclast, Osteocyte, Tooth Extraction, Toxicity
How to Cite
References
[1] Benbrook CM. Trends in glyphosate herbicide use in the United States and globally. Environ Sci Eur. 2016;28(1):3. [DOI: 10.1186/s12302-016-0070-0]
[2] Antier C, Kudsk P, Reboud X, Ulber L, Baret PV, Messéan A. Glyphosate use in the European agricultural sector and a framework for its further monitoring. Sustainability. 2020;12(14):5682. [DOI: 10.3390/su12145682]
[3] Martins-Gomes C, Silva TL, Andreani T, Silva AM. Glyphosate vs. glyphosate-based herbicides exposure: a review on their toxicity. J Xenobiot. 2022;12(1):21-40. [DOI: 10.3390/jox12010003]
[4] Marino M, Mele E, Viggiano A, Nori SL, Meccariello R, Santoro A. Pleiotropic outcomes of glyphosate exposure: from organ damage to effects on inflammation, cancer, reproduction and development. Int J Mol Sci. 2021;22(22):12606. [DOI: 10.3390/ijms222212606]
[5] Larsen K, Najle R, Lifschitz A, Virkel G. Effects of sub-lethal exposure of rats to the herbicide glyphosate in drinking water: glutathione transferase enzyme activities, levels of reduced glutathione and lipid peroxidation in liver, kidneys and small intestine. Environ Toxicol Pharmacol. 2012;34(3):811-8. [DOI: 10.1016/j.etap.2012.08.003]
[6] Peillex C, Pelletier M. The impact and toxicity of glyphosate and glyphosate-based herbicides on health and immunity. J Immunotoxicol. 2020;17(1):163-74. [DOI: 10.1080/1547691X.2020.1804400]
[7] Kryston TB, Georgiev AB, Pissis P, Georgakilas AG. Role of oxidative stress and DNA damage in human carcinogenesis. Mutat Res. 2011;711(1-2):193-201. [DOI: 10.1016/j.mrfmmm.2010.12.016]
[8] Ogura S, Shimosawa T. Oxidative stress and organ damage. Curr Hypertens Rep. 2014;16(8):452. [DOI: 10.1007/s11906-014-0452-5]
[9] Qi L, Dong YM, Chao H, Zhao P, Ma SL, Li G. Glyphosate-based herbicide disrupts energy metabolism and activates inflammatory response through oxidative stress in mouse liver. Chemosphere. 2023;315:137751. [DOI: 10.1016/j.chemosphere.2023.137751]
[10] Tang J, Hu P, Li Y, Win-Shwe TT, Li C. Ion imbalance is involved in the mechanisms of liver oxidative damage in rats exposed to glyphosate. Front Physiol. 2017;8:1083. [DOI: 10.3389/fphys.2017.01083]
[11] Jasper R, Locatelli GO, Pilati C, Locatelli C. Evaluation of biochemical, hematological and oxidative parameters in mice exposed to the herbicide glyphosate-Roundup. Interdiscip Toxicol. 2012;5(3):133-40. [DOI: 10.2478/v10102-012-0022-5]
[12] Wang R, Chen J, Ding F, Zhang L, Wu X, Wan Y, et al. Renal tubular injury induced by glyphosate combined with hard water: the role of cytosolic phospholipase A2. Ann Transl Med. 2021;9(2):130. [DOI: 10.21037/atm-20-7739]
[13] Nacano BRM, Convento MB, de Oliveira AS, Castino R, Castino B, Razvickas CV, et al. Effects of glyphosate herbicide ingestion on kidney function in rats on a balanced diet. J Bras Nefrol. 2024;46(2):e20230043. [DOI: 10.1590/2175-8239-JBN-2023-0043en]
[14] El-Shenawy NS. Oxidative stress responses of rats exposed to Roundup and its active ingredient glyphosate. Environ Toxicol Pharmacol. 2009;28(3):379-85. [DOI: 10.1016/j.etap.2009.06.001]
[15] Milić M, Žunec S, Micek V, Kašuba V, Mikolić A, Tariba Lovaković B, et al. Oxidative stress, cholinesterase activity, and DNA damage in the liver, whole blood, and plasma of Wistar rats following a 28-day exposure to glyphosate. Arh Hig Rada Toksikol. 2018;69(2):154-68. [DOI: 10.2478/aiht-2018-69-3114]
[16] Bonini MG, Rota C, Tomasi A, Mason RP. The oxidation of 2′,7′-dichlorofluorescin to reactive oxygen species: a self-fulfilling prophecy? Free Radic Biol Med. 2006;40(6):968-75. [DOI: 10.1016/j.freeradbiomed.2005.10.042]
[17] Forman HJ, Augusto O, Brigelius-Flohe R, Dennery PA, Kalyanaraman B, Ischiropoulos H, et al. Even free radicals should follow some rules: a guide to free radical research terminology and methodology. Free Radic Biol Med. 2015;78:233-5. [DOI: 10.1016/j.freeradbiomed.2014.10.504]
[18] Gibson-Corley KN, Olivier AK, Meyerholz DK. Principles for valid histopathologic scoring in research. Vet Pathol. 2013;50(6):1007-15. [DOI: 10.1177/0300985813485099]
[19] Street JM, Souza ACP, Alvarez-Prats A, Horino T, Hu X, Yuen PST, et al. Automated quantification of renal fibrosis with Sirius Red and polarization contrast microscopy. Physiol Rep. 2014;2(7):e12088. [DOI: 10.14814/phy2.12088]
- Abstract Viewed: 0 times
- 53790 Downloaded: 0 times