Dig1 protects against cell death provoked by glyphosate-based herbicides in human liver cell lines
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BACKGROUND: Worldwide used pesticides containing different adjuvants like Roundup formulations, which are glyphosate-based herbicides, can provoke some in vivo toxicity and in human cells. These pesticides are commonly found in the environment, surface waters and as food residues of Roundup tolerant genetically modified plants. In order to know their effects on cells from liver, a major detoxification organ, we have studied their mechanism of action and possible protection by precise medicinal plant extracts called Dig1. METHODS: The cytotoxicity pathways of four formulations of glyphosate-based herbicides were studied using human hepatic cell lines HepG2 and Hep3B, known models to study xenobiotic effects. We monitored mitochondrial succinate dehydrogenase activity and caspases 3/7 for cell mortality and protection by Dig1, as well as cytochromes P450 1A1, 1A2, 3A4 and 2C9 and glutathione-S-transferase to approach the mechanism of actions. RESULTS: All the four Roundup formulations provoke liver cell death, with adjuvants having stronger effects than glyphosate alone. Hep3B are 3-5 times more sensitive over 48 h. Caspases 3/7 are greatly activated in HepG2 by Roundup at non-cytotoxic levels, and some apoptosis induction by Roundup is possible together with necrosis. CYP3A4 is specifically enhanced by Roundup at doses 400 times less than used in agriculture (2%). CYP1A2 is increased to a lesser extent together with glutathione-S-transferase (GST) down-regulation. Dig 1, non cytotoxic and not inducing caspases by itself, is able to prevent Roundup-induced cell death in a time-dependant manner with an important efficiency of up to 89%, within 48 h. In addition, we evidenced that it prevents Caspases 3/7 activation and CYP3A4 enhancement, and not GST reduction, but in turn it slightly inhibited CYP2C9 when added before Roundup. CONCLUSION: Roundup is able to provoke intracellular disruption in hepatic cell lines at different levels, but a mixture of medicinal plant extracts Dig1 can protect to some extent human cell lines against this pollutants. All this system constitutes a tool for studying liver intoxication and detoxification.
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The ultrastructural findings are consistent with the well-documented toxic effect of very low dilutions of R on apoptosis, mitochondrial function, and cell membrane degradation inducing necrosis of hepatocytes and other cell lines.
“This is consistent with the well-documented toxic effect of very low dilutions of R on apoptosis, mitochondrial function, and cell membrane degradation inducing necrosis of hepatocytes, and other cell lines (Benachour and Seralini, 2009;Benachour et al., 2007;Gasnier et al., 2010;Peixoto, 2005).”
From RETRACTED: Long term toxicity of a Roundup herbicide and a Roundup-tolerant genetically modified maize (2012) · cites this paper as Gasnier et al., 2010
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HISTOPATHOLOGICAL EFFECTS OF GLYPHOSATE HERBICIDE ON DIFFERENT ORGANS OF MALE AND FEMALE ALBINO RATS
El–Abd, N. (2015) · Journal of Plant Protection and Pathology /Journal of Plant Protection and Pathology · doi:10.21608/jppp.2015.75448 · Cited by 1 · see citing works
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Peters, L. P. (2011) · doi:10.11606/d.11.2011.tde-28062011-151621 · Cited by 1 · see citing works
Игоревна, М. Д., Rakitskii, V. N., Fomina, M. A., Kiryushin, V. A., & Motalova, T. V. (2020) · Health Care of the Russian Federation · doi:10.46563/0044-197x-2020-64-6-351-357
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- Authors
- Gasnier, C., Benachour, N., Clair, E., Travert, C., Langlois, F., Laurant, C., Decroix-Laporte, C., & Séralini, G.-E.
- Affiliations
- Université de Caen Normandie (FR)
- Venue
- Journal of Occupational Medicine and Toxicology
- Published
- 2010-10-27
- Volume
- 5
- Issue
- 1
- Pages
- 29-29
- ISSN
- 1745-6673 (ISSN-L)
- PMC
- PMC2987375
- OpenAlex
- W2139673280
- Cited by
- 49
- References
- 50
- Citations by year
- 2025: 3 · 2023: 3 · 2022: 3 · 2021: 5 · 2020: 3 · 2019: 2 · 2018: 6 · 2017: 2 · 2016: 4 · 2015: 5 · 2014: 4 · 2013: 1 · 2012: 5
- FWCI
- 3.45
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Journal of Occupational Medicine and Toxicology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Fondation Denis Guichard
- Région Normandie
- Topics
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Pesticide Exposure and Toxicity
- Health Sciences › Medicine › Surgery › Paraquat toxicity studies and treatments
- Physical Sciences › Environmental Science › Pollution › Pesticide and Herbicide Environmental Studies
- Keywords
- glyphosate-based herbicides, Roundup, herbicide adjuvants, hepatotoxicity, hepatocyte death, apoptosis, necrosis, caspase-3/7 activation, CYP3A4, CYP1A2, glutathione S-transferase, medicinal plant extracts, HepG2 cells, Hep3B cells, xenobiotic detoxification, pesticide toxicity
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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