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      Glyphosate-induced changes in the expression of galanin and GALR1, GALR2 and GALR3 receptors in the porcine small intestine wall

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          Abstract

          Glyphosate is the active ingredient of glyphosate-based herbicides and the most commonly used pesticide in the world. The goal of the present study was to verify whether low doses of glyphosate (equivalent to the environmental exposure) evoke changes in galanin expression in intramural neurons in the small intestine in pigs and to quantitatively determine changes in the level of galanin receptor encoding mRNA (GALR1, GALR2, GALR3) in the small intestine wall. The experiment was conducted on 15 sexually immature gilts divided into three study groups: control (C)—animals receiving empty gelatin capsules; experimental 1 (G1)—animals receiving a low dose of glyphosate (0.05 mg/kg b.w./day); experimental 2 (G2)—animals receiving a higher dose of glyphosate (0.5 mg/kg b.w./day) orally in gelatine capsules for 28 days. Glyphosate ingestion led to an increase in the number of GAL-like immunoreactive intramural neurons in the porcine small intestine. The results of RT-PCR showed a significant increase in the expression of mRNA, which encodes the GAL-receptors in the ileum, a decreased expression in the duodenum and no significant changes in the jejunum. Additionally, intoxication with glyphosate increased the expression of SOD2-encoding mRNA in the duodenum and decreased it in the jejunum and ileum, but it did not affect SOD1 expression. The results suggest that it may be a consequence of the cytotoxic and/or neurotoxic properties of glyphosate and/or its ability to induce oxidative stress.

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          The enteric nervous system and neurogastroenterology.

          Neurogastroenterology is defined as neurology of the gastrointestinal tract, liver, gallbladder and pancreas and encompasses control of digestion through the enteric nervous system (ENS), the central nervous system (CNS) and integrative centers in sympathetic ganglia. This Review provides a broad overview of the field of neurogastroenterology, with a focus on the roles of the ENS in the control of the musculature of the gastrointestinal tract and transmucosal fluid movement. Digestion is controlled through the integration of multiple signals from the ENS and CNS; neural signals also pass between distinct gut regions to coordinate digestive activity. Moreover, neural and endocrine control of digestion is closely coordinated. Interestingly, the extent to which the ENS or CNS controls digestion differs considerably along the digestive tract. The importance of the ENS is emphasized by the life-threatening effects of certain ENS neuropathies, including Hirschsprung disease and Chagas disease. Other ENS disorders, such as esophageal achalasia and gastroparesis, cause varying degrees of dysfunction. The neurons in enteric reflex pathways use a wide range of chemical messengers that signal through an even wider range of receptors. These receptors provide many actual and potential targets for modifying digestive function.
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            Concerns over use of glyphosate-based herbicides and risks associated with exposures: a consensus statement

            The broad-spectrum herbicide glyphosate (common trade name “Roundup”) was first sold to farmers in 1974. Since the late 1970s, the volume of glyphosate-based herbicides (GBHs) applied has increased approximately 100-fold. Further increases in the volume applied are likely due to more and higher rates of application in response to the widespread emergence of glyphosate-resistant weeds and new, pre-harvest, dessicant use patterns. GBHs were developed to replace or reduce reliance on herbicides causing well-documented problems associated with drift and crop damage, slipping efficacy, and human health risks. Initial industry toxicity testing suggested that GBHs posed relatively low risks to non-target species, including mammals, leading regulatory authorities worldwide to set high acceptable exposure limits. To accommodate changes in GBH use patterns associated with genetically engineered, herbicide-tolerant crops, regulators have dramatically increased tolerance levels in maize, oilseed (soybeans and canola), and alfalfa crops and related livestock feeds. Animal and epidemiology studies published in the last decade, however, point to the need for a fresh look at glyphosate toxicity. Furthermore, the World Health Organization’s International Agency for Research on Cancer recently concluded that glyphosate is “probably carcinogenic to humans.” In response to changing GBH use patterns and advances in scientific understanding of their potential hazards, we have produced a Statement of Concern drawing on emerging science relevant to the safety of GBHs. Our Statement of Concern considers current published literature describing GBH uses, mechanisms of action, toxicity in laboratory animals, and epidemiological studies. It also examines the derivation of current human safety standards. We conclude that: (1) GBHs are the most heavily applied herbicide in the world and usage continues to rise; (2) Worldwide, GBHs often contaminate drinking water sources, precipitation, and air, especially in agricultural regions; (3) The half-life of glyphosate in water and soil is longer than previously recognized; (4) Glyphosate and its metabolites are widely present in the global soybean supply; (5) Human exposures to GBHs are rising; (6) Glyphosate is now authoritatively classified as a probable human carcinogen; (7) Regulatory estimates of tolerable daily intakes for glyphosate in the United States and European Union are based on outdated science. We offer a series of recommendations related to the need for new investments in epidemiological studies, biomonitoring, and toxicology studies that draw on the principles of endocrinology to determine whether the effects of GBHs are due to endocrine disrupting activities. We suggest that common commercial formulations of GBHs should be prioritized for inclusion in government-led toxicology testing programs such as the U.S. National Toxicology Program, as well as for biomonitoring as conducted by the U.S. Centers for Disease Control and Prevention.
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              Conclusion on the peer review of the pesticide risk assessment of the active substance glyphosate

              (2015)
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                Author and article information

                Contributors
                katarzyna.palus@uwm.edu.pl
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                17 April 2024
                17 April 2024
                2024
                : 14
                : 8905
                Affiliations
                [1 ]Department of Clinical Physiology, Faculty of Veterinary Medicine, University of Warmia and Mazury, ( https://ror.org/05s4feg49) Oczapowskiego 13, 10-719 Olsztyn, Poland
                [2 ]Department of Pathophysiology, Forensic Veterinary Medicine and Administration, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, ( https://ror.org/05s4feg49) Oczapowskiego 13, 10-719 Olsztyn, Poland
                [3 ]GRID grid.433017.2, ISNI 0000 0001 1091 0698, Division of Reproductive Biology, , Institute of Animal Reproduction and Food Research of the Polish Academy of Sciences, ; Tuwima 10, 10-078 Olsztyn, Poland
                Article
                59581
                10.1038/s41598-024-59581-8
                11024183
                38632282
                a4c90da1-55b7-4be0-a762-e4916326b082
                © The Author(s) 2024

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 11 September 2023
                : 12 April 2024
                Funding
                Funded by: the National Science Centre in Poland
                Award ID: 2020/04/X/NZ7/00338
                Award Recipient :
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                Article
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                © Springer Nature Limited 2024

                Uncategorized
                galanin,galanin receptors,glyphosate,enteric nervous system,small intestine,neurophysiology

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