Protective effects of boric acid against glyphosate-induced gastrointestinal toxicity in rats: insights from oxidative stress, inflammatory and histopathological markers
Yıl 2025,
Cilt: 10 Sayı: 3, 121 - 129, 30.09.2025
Tuba Doğan
,
Ömercan Alat
,
İsmail Bolat
Öz
Glyphosate (GLY), a widely used herbicide, has been associated with gastrointestinal toxicity primarily via oxidative stress and inflammation. This study aimed to evaluate the protective role of boric acid (BA) against GLY-induced stomach and intestinal injury in rats. Adult male Sprague-Dawley rats were divided into control, GLY-treated, BA-treated, and GLY+BA co-treated groups. Both GLY (150 mg/kg/day) and BA (100 mg/kg/day) were administered orally for 7 consecutive days. Gastrointestinal tissues were assessed for oxidative stress markers including superoxide dismutase (SOD) and catalase (CAT), as well as gene expression via real-time polymerase chain reaction (PCR). Inflammatory markers tumor necrosis factor-alpha (TNF-α) and nuclear factor kappa B (NF-κB) were analyzed by Western blot. Histopathological evaluations were performed using hematoxylin-eosin (H&E) staining, and oxidative DNA damage was assessed by immunohistochemical detection of 8-hydroxy-2'-deoxyguanosine (8-OHdG). GLY exposure significantly increased TNF-α and NF-κB expression while downregulating SOD and CAT levels, leading to mucosal injury and marked histopathological alterations. In the GLY+BA group, histopathological evaluation revealed reduced mucosal damage and substantial preservation of glandular architecture. These results suggest that BA confers protection against GLY-induced gastrointestinal toxicity, likely through its antioxidant and anti-inflammatory properties.
Etik Beyan
All experimental procedures involving animals have been approved by the Atatürk University Local Ethics Committee for Animal Experiments (Approval Number: 2025/06/118).
Kaynakça
-
Battisti, L., Potrich, M., Sampaio, A. R., de Castilhos Ghisi, N., Costa-Maia, F. M., Abati, R., … & Sofia, S. H. (2021). Is glyphosate toxic to bees? A meta-analytical review. Science of The Total Environment, 767, 145397. https://doi.org/10.1016/J.SCITOTENV.2021.145397
-
Martins-Gomes, C., Silva, T. L., Andreani, T., & Silva, A. M. (2022). Glyphosate vs. glyphosate-based herbicides exposure: A review on their toxicity. Journal of Xenobiotics, 12, 21-40. https://doi.org/10.3390/JOX12010003
-
de Maria Serra, F., Parizi, J. L. S., de Mello Odorizzi, G. A. S., Sato, G. M. R. H., Patrão, I. B., Chagas, P. H. N., … & Nai, G. A. (2021). Subchronic exposure to a glyphosate-based herbicide causes dysplasia in the digestive tract of Wistar rats. Environmental Science and Pollution Research, 28, 61477-61496. https://doi.org/10.1007/s11356-021-15051-6
-
Tang, Q., Tang, J., Ren, X., & Li, C. (2020). Glyphosate exposure induces inflammatory responses in the small intestine and alters gut microbial composition in rats. Environmental Pollution, 261, 114129. https://doi.org/10.1016/J.ENVPOL.2020.114129
-
Benbrook, C. M. (2019). How did the US EPA and IARC reach diametrically opposed conclusions on the genotoxicity of glyphosate-based herbicides? Environmental Sciences Europe, 31(2), 1-16. https://doi.org/10.1186/s12302-018-0184-7
-
Tarazona, J. V., Court-Marques, D., Tiramani, M., Reich, H., Pfeil, R., Istace, F., & Crivellente, F. (2017). Glyphosate toxicity and carcinogenicity: A review of the scientific basis of the European Union assessment and its differences with IARC. Archives of Toxicology, 91, 2723-2743. https://doi.org/10.1007/s00204-017-1962-5
-
Dogan, T., Yildirim, B.A., & Kapakin, K.A.T. (2024). Investigation of the effects of crocin on inflammation, oxidative stress, apoptosis, NF-κB, TLR-4 and Nrf-2/ HO-1 pathways in gentamicin-induced nephrotoxicity in rats. Environmental Toxicology and Pharmacology, 106, 104374. https://doi.org/10.1016/J.ETAP.2024.104374
-
Dai, H., Wang, J., Li, Y., & Lv, Z. (2024). Hawthorn-leaf flavonoid alleviate intestinal health and microbial dysbiosis problems induced by glyphosate. Ecotoxicology and Environmental Safety, 284, 116901. https://doi.org/10.1016/J.ECOENV.2024.116901
-
Mazuryk, J., Klepacka, K., Kutner, W., & Sharma, P. S. (2024). Glyphosate: Hepatotoxicity, nephrotoxicity, hemotoxicity, carcinogenicity, and clinical cases of endocrine, reproductive, cardiovascular, and pulmonary system intoxication. ACS Pharmacology and Translational Science, 7(5), 1205-1236. https://doi.org/10.1021/acsptsci.4c00046
-
Cengiz, M., Ayhanci, A., Akkemik, E., Şahin, İ. K., Gür, F., Bayrakdar, A., … & Gür, B. (2022). The role of Bax/ Bcl-2 and Nrf2-Keap-1 signaling pathways in mediating the protective effect of boric acid on acrylamide-induced acute liver injury in rats. Life Sciences, 307, 120864. https://doi.org/10.1016/J.LFS.2022.120864
-
İlhan, A. O., Can, B., Kar, F., Gündoğdu, A. Ç., Söğüt, İ., & Kanbak, G. (2023). An investigation into the protective effects of various doses of boric acid on liver, kidney, and brain tissue damage caused by high levels of acute alcohol consumption. Biological Trace Element Research, 201(11), 5346-5357. https://doi.org/10.1007/s12011-023-03699-9
-
Aktas Senocak, E., Utlu, N., Kurt, S., Kucukler, S., & Kandemir, F. M. (2024). Sodium pentaborate prevents acetaminophen-induced hepatorenal injury by suppressing oxidative stress, lipid peroxidation, apoptosis, and inflammatory cytokines in rats. Biological Trace Element Research, 202(3), 1164-1173. https://doi.org/10.1007/s12011-023-03755-4
-
Adewale, O. O., Adebisi, O. A., Ojurongbe, T. A., Adekomi, D. A., Babatunde, I. O., & Adebayo, E. O. (2023). Xylopia aethiopica suppresses markers of oxidative stress, inflammation, and cell death in the brain of Wistar rats exposed to glyphosate. Environmental Science and Pollution Research, 30, 60946-60957. https://doi.org/10.1007/s11356-023-26470-y
-
Livak, K. J. & Schmittgen, T. D. (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method. Methods, 25(4), 402-408. https://doi.org/10.1006/METH.2001.1262
-
Bass, J. J., Wilkinson, D. J., Rankin, D., Phillips, B. E., Szewczyk, N. J., Smith, K., & Atherton, P. J. (2017). An overview of technical considerations for Western blotting applications to physiological research. Scandinavian Journal of Medicine and Science in Sports, 27(1), 4-25. https://doi.org/10.1111/SMS.12702
-
Bolat, M., Celebi, F., Sengul, E., Cinar, I., Yildirim, S., & Bolat, I. (2025). Investigation of the protective effect of beta caryophyllene against indomethacin-induced gastric ulcer in rats: In vivo and in vitro study. Naunyn- Schmiedeberg’s Archives of Pharmacology, (2025). https://doi.org/10.1007/S00210-025-04269-7
-
Danisman, B., Cicek, B., Yildirim, S., Bolat, I., Kantar, D., Golokhvast, K. S., … & Taghizadehghalehjoughi, A. (2023). Carnosic acid ameliorates indomethacin-induced gastric ulceration in rats by alleviating oxidative stress and inflammation. Biomedicines, 11(3), 829. https://doi.org/10.3390/BIOMEDICINES11030829
-
Benedetti A. L., Vituri, C. D. L., Trentin, A.G., Domingues, M. A. C., & Alvarez-Silva, M. (2004). The effects of sub-chronic exposure of Wistar rats to the herbicide Glyphosate-Biocarb®. Toxicology Letters, 153(2), 227- 232. https://doi.org/10.1016/J.TOXLET.2004.04.008
-
Astiz, M., de Alaniz, M. J. T., & Marra, C. A. (2009). Antioxidant defense system in rats simultaneously intoxicated with agrochemicals. Environmental Toxicology and Pharmacology, 28(3), 465-473. https://doi.org/10.1016/J.ETAP.2009.07.009
-
Mesnage, R., Phedonos, A., Biserni, M., Arno, M., Balu, S., Corton, J. C., … & Antoniou, M. N. (2017). Evaluation of estrogen receptor alpha activation by glyphosate-based herbicide constituents. Food and Chemical Toxicology, 108(Part A) 30-42. https://doi.org/10.1016/J.FCT.2017.07.025
-
Winstone, J. K., Pathak, K. V., Winslow, W., Piras, I. S., White, J., Sharma, R., & Velazquez, R. (2022). Glyphosate infiltrates the brain and increases pro-inflammatory cytokine TNFα: Implications for neurodegenerative disorders. Journal of Neuroinflammation, 19, 193. https://doi.org/10.1186/S12974-022-02544-5
-
Scorei, R. I. & Rotaru, P. (2011). Calcium fructoborate- Potential anti-inflammatory agent. Biological Trace Element Research, 143, 1223-1238. https://doi.org/10.1007/S12011-011-8972-6
-
Jabbar, A. A. J., Alamri, Z. Z., Abdulla, M. A., Salehen, N. A., Ibrahim, I. A. A., Hassan, R. R., &… Almutawif, Y. A. (2024). Boric acid (boron) attenuates AOM-induced colorectal cancer in rats by augmentation of apoptotic and antioxidant mechanisms. Biological Trace Element Research, 202, 2702-2719. https://doi.org/10.1007/S12011-023-03864-0
-
Karimkhani, H., Ozkoc, M., Shojaolsadati, P., Uzuner, K., Burukoglu Donmez, D., & Kanbak, G. (2021). Protective effect of boric acid and omega-3 on myocardial infarction in an experimental rat model. Biological Trace Element Research, 199, 2612-2620. https://doi.org/10.1007/S12011-020-02360-Z
-
Bolognesi, C., Bonatti, S., Degan, P., Gallerani, E., Peluso, M., Rabboni, R., … & Abbondandolo, A. (1997). Genotoxic activity of glyphosate and its technical formulation roundup. Journal of Agricultural and Food Chemistry, 45(5), 1957-1962. https://doi.org/10.1021/jf9606518
Sıçanlarda glifosat kaynaklı gastrointestinal toksisiteye karşı borik asidin koruyucu etkileri: Oksidatif stres, inflamasyon ve histopatolojik belirteçler üzerinden bulgular
Yıl 2025,
Cilt: 10 Sayı: 3, 121 - 129, 30.09.2025
Tuba Doğan
,
Ömercan Alat
,
İsmail Bolat
Öz
Yaygın olarak kullanılan bir herbisit olan glifosat (GLY), öncelikle oksidatif stres ve inflamasyon yoluyla gastrointestinal toksisite ile ilişkilendirilmektedir. Bu çalışma, sıçanlarda GLY kaynaklı mide ve bağırsak hasarına karşı borik asidin (BA) koruyucu rolünü değerlendirmeyi amaçlamıştır. Yetişkin erkek Sprague-Dawley sıçanları kontrol, GLY ile tedavi edilen, BA ile tedavi edilen ve GLY+BA birlikte tedavi edilen gruplara ayrıldı. Hem GLY (150 mg/kg/gün) hem de BA (100 mg/kg/gün) 7 ardışık gün boyunca oral olarak uygulanmıştır. Gastrointestinal dokular, süperoksit dismutaz (SOD) ve katalaz (CAT) dahil olmak üzere oksidatif stres belirteçleri ve gerçek zamanlı polimeraz zincir reaksiyonu (PCR) yoluyla gen ekspresyonu açısından değerlendirilmiştir. İnflamatuar belirteçler olan tümör nekroz faktörü-alfa (TNF-α) ve nükleer faktör kappa B (NF-κB), Western blot ile analiz edilmiştir. Histopatolojik değerlendirmeler hematoksilen-eozin (H&E) boyama kullanılarak gerçekleştirilmiş ve oksidatif DNA hasarı, 8-hidroksi-2'-deoksiguanozin (8-OHdG) immünohistokimyasal tespiti ile değerlendirilmiştir. GLY maruziyeti, TNF-α ve NF-κB ekspresyonunu anlamlı olarak artırırken, SOD ve CAT seviyelerini düşürerek mukozal hasara ve belirgin histopatolojik değişikliklere yol açmıştır. GLY+BA grubunda, histopatolojik değerlendirme mukozal hasarın azaldığını ve glandüler yapının anlamlı olarak korunduğunu ortaya koymuştur. Bu sonuçlar, BA'nın muhtemelen antioksidan ve anti-inflamatuar özellikleri sayesinde GLY kaynaklı gastrointestinal toksisiteye karşı koruma sağladığını göstermektedir.
Etik Beyan
Hayvanlar üzerinde yapılan tüm deneysel işlemler Atatürk Üniversitesi Hayvan Deneyleri Yerel Etik Kurulu tarafından onaylanmıştır (Onay Numarası: 2025/06/118).
Kaynakça
-
Battisti, L., Potrich, M., Sampaio, A. R., de Castilhos Ghisi, N., Costa-Maia, F. M., Abati, R., … & Sofia, S. H. (2021). Is glyphosate toxic to bees? A meta-analytical review. Science of The Total Environment, 767, 145397. https://doi.org/10.1016/J.SCITOTENV.2021.145397
-
Martins-Gomes, C., Silva, T. L., Andreani, T., & Silva, A. M. (2022). Glyphosate vs. glyphosate-based herbicides exposure: A review on their toxicity. Journal of Xenobiotics, 12, 21-40. https://doi.org/10.3390/JOX12010003
-
de Maria Serra, F., Parizi, J. L. S., de Mello Odorizzi, G. A. S., Sato, G. M. R. H., Patrão, I. B., Chagas, P. H. N., … & Nai, G. A. (2021). Subchronic exposure to a glyphosate-based herbicide causes dysplasia in the digestive tract of Wistar rats. Environmental Science and Pollution Research, 28, 61477-61496. https://doi.org/10.1007/s11356-021-15051-6
-
Tang, Q., Tang, J., Ren, X., & Li, C. (2020). Glyphosate exposure induces inflammatory responses in the small intestine and alters gut microbial composition in rats. Environmental Pollution, 261, 114129. https://doi.org/10.1016/J.ENVPOL.2020.114129
-
Benbrook, C. M. (2019). How did the US EPA and IARC reach diametrically opposed conclusions on the genotoxicity of glyphosate-based herbicides? Environmental Sciences Europe, 31(2), 1-16. https://doi.org/10.1186/s12302-018-0184-7
-
Tarazona, J. V., Court-Marques, D., Tiramani, M., Reich, H., Pfeil, R., Istace, F., & Crivellente, F. (2017). Glyphosate toxicity and carcinogenicity: A review of the scientific basis of the European Union assessment and its differences with IARC. Archives of Toxicology, 91, 2723-2743. https://doi.org/10.1007/s00204-017-1962-5
-
Dogan, T., Yildirim, B.A., & Kapakin, K.A.T. (2024). Investigation of the effects of crocin on inflammation, oxidative stress, apoptosis, NF-κB, TLR-4 and Nrf-2/ HO-1 pathways in gentamicin-induced nephrotoxicity in rats. Environmental Toxicology and Pharmacology, 106, 104374. https://doi.org/10.1016/J.ETAP.2024.104374
-
Dai, H., Wang, J., Li, Y., & Lv, Z. (2024). Hawthorn-leaf flavonoid alleviate intestinal health and microbial dysbiosis problems induced by glyphosate. Ecotoxicology and Environmental Safety, 284, 116901. https://doi.org/10.1016/J.ECOENV.2024.116901
-
Mazuryk, J., Klepacka, K., Kutner, W., & Sharma, P. S. (2024). Glyphosate: Hepatotoxicity, nephrotoxicity, hemotoxicity, carcinogenicity, and clinical cases of endocrine, reproductive, cardiovascular, and pulmonary system intoxication. ACS Pharmacology and Translational Science, 7(5), 1205-1236. https://doi.org/10.1021/acsptsci.4c00046
-
Cengiz, M., Ayhanci, A., Akkemik, E., Şahin, İ. K., Gür, F., Bayrakdar, A., … & Gür, B. (2022). The role of Bax/ Bcl-2 and Nrf2-Keap-1 signaling pathways in mediating the protective effect of boric acid on acrylamide-induced acute liver injury in rats. Life Sciences, 307, 120864. https://doi.org/10.1016/J.LFS.2022.120864
-
İlhan, A. O., Can, B., Kar, F., Gündoğdu, A. Ç., Söğüt, İ., & Kanbak, G. (2023). An investigation into the protective effects of various doses of boric acid on liver, kidney, and brain tissue damage caused by high levels of acute alcohol consumption. Biological Trace Element Research, 201(11), 5346-5357. https://doi.org/10.1007/s12011-023-03699-9
-
Aktas Senocak, E., Utlu, N., Kurt, S., Kucukler, S., & Kandemir, F. M. (2024). Sodium pentaborate prevents acetaminophen-induced hepatorenal injury by suppressing oxidative stress, lipid peroxidation, apoptosis, and inflammatory cytokines in rats. Biological Trace Element Research, 202(3), 1164-1173. https://doi.org/10.1007/s12011-023-03755-4
-
Adewale, O. O., Adebisi, O. A., Ojurongbe, T. A., Adekomi, D. A., Babatunde, I. O., & Adebayo, E. O. (2023). Xylopia aethiopica suppresses markers of oxidative stress, inflammation, and cell death in the brain of Wistar rats exposed to glyphosate. Environmental Science and Pollution Research, 30, 60946-60957. https://doi.org/10.1007/s11356-023-26470-y
-
Livak, K. J. & Schmittgen, T. D. (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method. Methods, 25(4), 402-408. https://doi.org/10.1006/METH.2001.1262
-
Bass, J. J., Wilkinson, D. J., Rankin, D., Phillips, B. E., Szewczyk, N. J., Smith, K., & Atherton, P. J. (2017). An overview of technical considerations for Western blotting applications to physiological research. Scandinavian Journal of Medicine and Science in Sports, 27(1), 4-25. https://doi.org/10.1111/SMS.12702
-
Bolat, M., Celebi, F., Sengul, E., Cinar, I., Yildirim, S., & Bolat, I. (2025). Investigation of the protective effect of beta caryophyllene against indomethacin-induced gastric ulcer in rats: In vivo and in vitro study. Naunyn- Schmiedeberg’s Archives of Pharmacology, (2025). https://doi.org/10.1007/S00210-025-04269-7
-
Danisman, B., Cicek, B., Yildirim, S., Bolat, I., Kantar, D., Golokhvast, K. S., … & Taghizadehghalehjoughi, A. (2023). Carnosic acid ameliorates indomethacin-induced gastric ulceration in rats by alleviating oxidative stress and inflammation. Biomedicines, 11(3), 829. https://doi.org/10.3390/BIOMEDICINES11030829
-
Benedetti A. L., Vituri, C. D. L., Trentin, A.G., Domingues, M. A. C., & Alvarez-Silva, M. (2004). The effects of sub-chronic exposure of Wistar rats to the herbicide Glyphosate-Biocarb®. Toxicology Letters, 153(2), 227- 232. https://doi.org/10.1016/J.TOXLET.2004.04.008
-
Astiz, M., de Alaniz, M. J. T., & Marra, C. A. (2009). Antioxidant defense system in rats simultaneously intoxicated with agrochemicals. Environmental Toxicology and Pharmacology, 28(3), 465-473. https://doi.org/10.1016/J.ETAP.2009.07.009
-
Mesnage, R., Phedonos, A., Biserni, M., Arno, M., Balu, S., Corton, J. C., … & Antoniou, M. N. (2017). Evaluation of estrogen receptor alpha activation by glyphosate-based herbicide constituents. Food and Chemical Toxicology, 108(Part A) 30-42. https://doi.org/10.1016/J.FCT.2017.07.025
-
Winstone, J. K., Pathak, K. V., Winslow, W., Piras, I. S., White, J., Sharma, R., & Velazquez, R. (2022). Glyphosate infiltrates the brain and increases pro-inflammatory cytokine TNFα: Implications for neurodegenerative disorders. Journal of Neuroinflammation, 19, 193. https://doi.org/10.1186/S12974-022-02544-5
-
Scorei, R. I. & Rotaru, P. (2011). Calcium fructoborate- Potential anti-inflammatory agent. Biological Trace Element Research, 143, 1223-1238. https://doi.org/10.1007/S12011-011-8972-6
-
Jabbar, A. A. J., Alamri, Z. Z., Abdulla, M. A., Salehen, N. A., Ibrahim, I. A. A., Hassan, R. R., &… Almutawif, Y. A. (2024). Boric acid (boron) attenuates AOM-induced colorectal cancer in rats by augmentation of apoptotic and antioxidant mechanisms. Biological Trace Element Research, 202, 2702-2719. https://doi.org/10.1007/S12011-023-03864-0
-
Karimkhani, H., Ozkoc, M., Shojaolsadati, P., Uzuner, K., Burukoglu Donmez, D., & Kanbak, G. (2021). Protective effect of boric acid and omega-3 on myocardial infarction in an experimental rat model. Biological Trace Element Research, 199, 2612-2620. https://doi.org/10.1007/S12011-020-02360-Z
-
Bolognesi, C., Bonatti, S., Degan, P., Gallerani, E., Peluso, M., Rabboni, R., … & Abbondandolo, A. (1997). Genotoxic activity of glyphosate and its technical formulation roundup. Journal of Agricultural and Food Chemistry, 45(5), 1957-1962. https://doi.org/10.1021/jf9606518