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Effects of boric acid on reproductive hormones and utero-ovarian tissues in female rats: A dose-response study

Yıl 2025, Cilt: 10 Sayı: 4, 150 - 155, 31.12.2025

Öz

Boric acid is a widely used form of boron, and its potential as a therapeutic agent is being increasingly investigated. This study aimed to evaluate the dose-dependent effects of oral boric acid administration on reproductive hormone levels and the histopathological architecture of ovarian and uterine tissues in female rats. Twenty-four young adult female rats were randomly divided into four groups: control, low-dose boric acid (10 mg/kg), medium-dose boric acid (100 mg/kg), and high-dose boric acid (1000 mg/kg). Boric acid or saline was administered orally once daily for 21 days. Serum estradiol and progesterone levels were measured and ovarian and uterine tissues were examined histopathologically. Low and medium doses of boric acid did not significantly alter estradiol or progesterone levels compared to controls (p>0.05). However, high-dose boric acid administration significantly decreased estradiol levels while increasing progesterone levels (p<0.05). Histological evaluation revealed dose-dependent pathological changes, including edema, vascular congestion, follicular degeneration in the ovaries, and hyperplasia of endometrial glands in the uterus, particularly prominent at high doses. Boric acid exposure at high doses could disrupt the hormonal balance and induce significant structural damage in reproductive tissues, suggesting a potential risk to female reproductive health. These findings emphasize the necessity for cautious evaluation of boric acid exposure levels, particularly given its widespread industrial and medical applications.

Kaynakça

  • Ince, S., Keles, H., Erdogan, M., Hazman, O., & Kucukkurt, I. (2012). Protective effect of boric acid against carbon tetrachloride-induced hepatotoxicity in mice, Drug and Chemical Toxicology, 35(3), 285-292. https://doi.org/10.3109/01480545.2011.607825
  • Karabağ Çoban, F., & Kuru, B. (2019). Effect of boron on trace element level and oxidative stress in paracetamol induced hepatotoxicity model. Journal of Boron, 4(2), 92-99. https://doi.org/10.30728/boron.518606
  • Koçak, Ö. F., Atila, A., Halıcı, Z., & Albayrak, M. (2022). Boron determination in serum and plasma of rats administered boron citrate. Journal of Boron, 7(2), 482-486. https://doi.org/10.30728/boron.1078402
  • Khaliq, H., Zhong, J., & Peng, K.-M. (2018). The physiological role of boron on health. Biological Trace Element Research, 186(1), 31-51. https://doi.org/10.1007/s12011-018-1284-3
  • Parikh, D., & Gohil, P. (2014). Role of estrogen and progesterone in human disorders: An overview. International Journal of Pharma Research & Review, 3(3), 62-71.
  • Estevez-Fregoso, E., Kilic, A., Rodríguez-Vera, D., Nicanor-Juárez, L. E., Romero-Rizo, C. E. M., Farfán-García, E. D., & Soriano-Ursúa, M. A. (2023). Effects of boron-containing compounds on liposoluble hormone functions. Inorganics, 11(2), 84. https://doi.org/10.3390/inorganics11020084
  • Faccio, L., Da Silva, A. S., Tonin, A. A., França, R. T., Gressler, L. T., Copetti, M. M., … & Monteiro, S. G. (2013). Serum levels of LH, FSH, estradiol and progesterone in female rats experimentally infected by Trypanosoma evansi. Experimental Parasitology, 135(1), 110-115. https://doi.org/10.1016/j.exppara.2013.06.008
  • Bello, M., Guadarrama-García, C., Velasco-Silveyra, L. M., Farfán-García, E. D., & Soriano-Ursúa, M. A. (2018). Several effects of boron are induced by uncoupling steroid hormones from their transporters in blood. Medical Hypotheses, 118, 78-83. https://doi.org/10.1016/j.mehy.2018.06.024
  • Sheng, M. H. C., Taper, L. J., Veit, H., Thomas, E. A., Ritchey, S. J., & Lau, K. H. W. (2001). Dietary boron supplementation enhances the effects of estrogen on bone mineral balance in ovariectomized rats. Biological Trace Element Research, 81, 29-45. https://doi.org/10.1385/BTER:81:1:29
  • Duydu, Y., Başaran, N., Üstündağ, A., Aydın, S., Ündeğer, Ü., Ataman, … & Bolt, H. M. (2016). Is boric acid toxic to reproduction in humans? Assessment of the animal reproductive toxicity data and epidemiological study results. Current Drug Delivery, 13(3), 324-329. https://doi.org/10.2174/1567201812666151029101514
  • Ku, W. W., & Chapin, R. E. (1994). Mechanism of the testicular toxicity of boric acid in rats: In vivo and in vitro studies. Environmental Health Perspectives, 102(Suppl 7), 99-105. https://doi.org/10.1289/ehp.94102s799
  • Bolt, H. M., Başaran, N., & Duydu, Y. (2020). Effects of boron compounds on human reproduction. Archives of Toxicology, 94, 717-724. https://doi.org/10.1007/s00204-020-02700-x
  • Hadrup, N., Frederiksen, M., & Sharma, A. K. (2021). Toxicity of boric acid, borax and other boron containing compounds: A review. Regulatory Toxicology and Pharmacology, 121, 104873. https://doi.org/10.1016/j.yrtph.2021.104873
  • Özdemir, Ç., Arslan, M., Küçük, A., Yığman, Z., & Dursun, A. D. (2023). Therapeutic efficacy of boric acid treatment on brain tissue and cognitive functions in rats with experimental Alzheimer’s disease. Drug Design, Development and Therapy, 17, 1453-1462. https://doi.org/10.2147/DDDT.S405963
  • Luna, L. G. (1968). Manual of histologic staining methods of the Armed Forces Institute of Pathology (3rd ed.). McGraw-Hill Book Company.
  • Başeğmez, M., & Doğan, M. F. (2024). Effects of boric acid on oxidant-antioxidant, proinflammatory cytokine levels, and biochemical parameters in aged rats. Pamukkale Medical Journal, 17(2), 369-379. https://doi.org/10.31362/patd.1438593
  • Wang, Y., Zhao, Y., & Chen, X. (2008). Experimental study on the estrogen-like effect of boric acid. Biological Trace Element Research, 121(2), 160-170. https://doi.org/10.1007/s12011-007-8041-3
  • Endo, Y., Iijima, T., Yamakoshi, Y., Fukasawa, H., Miyaura, C., Inada, M., … & Itai, A. (2001). Potent estrogen agonists based on carborane as a hydrophobic skeletal structure: A new medicinal application of boron clusters. Chemistry & Biology, 8(4), 341-355. https://doi.org/10.1016/S1074-5521(01)00016-3
  • Sheng, M. H.-C., Taper, L. J., Veit, H., Qian, H., Ritchey, S. J., & Lau, K.-H. W. (2001). Dietary boron supplementation enhanced the action of estrogen, but not that of parathyroid hormone, to improve trabecular bone quality in ovariectomized rats. Biological Trace Element Research, 82, 109-123. https://doi.org/10.1385/BTER:82:1-3:109
  • Chapin, R. E., & Ku, W. W. (1994). The reproductive toxicity of boric acid. Environmental Health Perspectives, 102(Suppl. 7), 87-91. https://doi.org/10.2307/3431969
  • Pizzorno, L. (2015). Nothing boring about boron. Integrative Medicine: A Clinician's Journal, 14(4), 35-48.
  • Agoreyo, F., & Onwegbu, V. (2015). Quantitative evaluation of serum progesterone levels in the three trimesters of pregnancy in albino rat. Journal of Applied Sciences and Environmental Management, 19(1), 77-79. https://doi.org/10.4314/jasem.v19i1.10
  • Westwood, F. R. (2008). The female rat reproductive cycle: A practical histological guide to staging. Toxicologic Pathology, 36(3), 375-384. https://doi.org/10.1177/0192623308315665
  • Lovick, T. A., & Zangrossi Jr., H. (2021). Effect of estrous cycle on behavior of females in rodent tests of anxiety. Frontiers in Psychiatry, 12, 711065. https://doi.org/10.3389/fpsyt.2021.711065
  • Naghii, M. R., Mofid, M., Asgari, A. R., Hedayati, M., & Daneshpour, M. S. (2011). Comparative effects of daily and weekly boron supplementation on plasma steroid hormones and proinflammatory cytokines. Journal of Trace Elements in Medicine and Biology, 25(1), 54-58. https://doi.org/10.1016/j.jtemb.2010.10.001
  • Duydu, Y., Başaran, N., Aydın, S., Üstündağ, A., Yalçin, C. Ö., Anlar, H. G., … & Bolt, H. M. (2018). Evaluation of FSH, LH, testosterone levels and semen parameters in male boron workers under extreme exposure conditions. Archives of Toxicology, 92, 3051-3059. https://doi.org/10.1007/s00204-018-2296-7
  • Karaman, E., & Yavuz, A. (2024). Boric acid protects the uterus and fallopian tubes from cyclophosphamideınduced toxicity in a rat model. Pharmaceuticals, 17(12), 1716. https://doi.org/10.3390/ph17121716
  • Aydın, M., Çağlayan, N., Kara, Ö., & Kara, M. (2025). Protective effect of boric acid on ovarian damage caused by endotoxaemia. Journal of Obstetrics and Gynaecology Research, 51(8), e70055. https://doi.org/10.1111/jog.70055
  • Watson, A. T. D., Sutherland, V. L., Cunny, H., Miller-Pinsler, L., Furr, J., Hebert, C., … & McIntyre, B. S. (2020). Postnatal effects of gestational and lactational gavage exposure to boric acid in the developing Sprague Dawley rat. Toxicological Sciences, 176(1), 65-73. https://doi.org/10.1093/toxsci/kfaa061
  • Duydu, Y., Başaran, N., Üstündağ, A., Aydın, S., Yalçın, C. Ö., Anlar, H. … & Bolt, H. M. (2018). Birth weights of newborns and pregnancy outcomes of environmentally boron-exposed females in Turkey. Archives of Toxicology, 92, 2475-2485. https://doi.org/10.1007/s00204-018-2238-4
  • Büyükgüzel, E., Büyükgüzel, K., Snela, M., Erdem, M., Radtke, K., Ziemnicki, K., & Adamski, Z. (2013). Effect of boric acid on antioxidant enzyme activity, lipid peroxidation, and ultrastructure of mid-gut and fat body of Galleria mellonella. Cell Biology and Toxicology, 29, 117-129. https://doi.org/10.1007/s10565-013-9240-7

Borik asidin dişi sıçanlarda üreme hormonları ve uterus-ovaryum dokuları üzerindeki etkileri: Doz-yanıt çalışması

Yıl 2025, Cilt: 10 Sayı: 4, 150 - 155, 31.12.2025

Öz

Borik asit, yaygın olarak kullanılan bir bor formu olup terapötik ajan olarak potansiyeli giderek daha fazla araştırılmaktadır. Bu çalışma, oral borik asit uygulamasının doz bağımlı etkilerini dişi sıçanlarda üreme hormon düzeyleri ile over ve uterus dokularının histopatolojik yapısı üzerinde değerlendirmeyi amaçlamıştır. Yirmi dört genç dişi sıçan rastgele olarak dört gruba ayrılmıştır: Kontrol, düşük doz borik asit (10 mg/kg), orta doz borik asit (100 mg/kg) ve yüksek doz borik asit (1000 mg/kg). Borik asit veya salin solüsyonu, 21 gün boyunca günde bir kez oral yolla uygulandı. Serum östradiol ve progesteron düzeyleri ölçüldü, over ve uterus dokuları histopatolojik olarak incelendi. Düşük ve orta doz borik asit uygulamaları, kontrol grubuna kıyasla östradiol ve progesteron düzeylerinde anlamlı değişiklik oluşturmadı (p>0,05). Ancak yüksek doz borik asit uygulaması, östradiol düzeylerini anlamlı olarak azaltırken progesteron düzeylerini artırdı (p<0,05). Histopatolojik değerlendirmede, doza bağlı olarak over dokusunda ödem, vasküler konjesyon ve foliküler dejenerasyon gözlendi. Uterus dokusunda ise özellikle yüksek dozlarda belirgin endometriyal bez hiperplazisi ve şiddetli vasküler hiperemi tespit edildi. Yüksek doz borik asit maruziyeti, hormonal dengeyi değiştirerek ve üreme dokularında belirgin yapısal hasara yol açabileceğinden, kadın üreme sağlığı açısından potansiyel risk oluşturabileceği sonucuna varılmıştır. Bu bulgular, borik asidin yaygın endüstriyel ve tıbbi uygulamaları göz önünde bulundurularak, maruziyet düzeylerinin dikkatle değerlendirilmesi gerekliliğini vurgulamaktadır.

Kaynakça

  • Ince, S., Keles, H., Erdogan, M., Hazman, O., & Kucukkurt, I. (2012). Protective effect of boric acid against carbon tetrachloride-induced hepatotoxicity in mice, Drug and Chemical Toxicology, 35(3), 285-292. https://doi.org/10.3109/01480545.2011.607825
  • Karabağ Çoban, F., & Kuru, B. (2019). Effect of boron on trace element level and oxidative stress in paracetamol induced hepatotoxicity model. Journal of Boron, 4(2), 92-99. https://doi.org/10.30728/boron.518606
  • Koçak, Ö. F., Atila, A., Halıcı, Z., & Albayrak, M. (2022). Boron determination in serum and plasma of rats administered boron citrate. Journal of Boron, 7(2), 482-486. https://doi.org/10.30728/boron.1078402
  • Khaliq, H., Zhong, J., & Peng, K.-M. (2018). The physiological role of boron on health. Biological Trace Element Research, 186(1), 31-51. https://doi.org/10.1007/s12011-018-1284-3
  • Parikh, D., & Gohil, P. (2014). Role of estrogen and progesterone in human disorders: An overview. International Journal of Pharma Research & Review, 3(3), 62-71.
  • Estevez-Fregoso, E., Kilic, A., Rodríguez-Vera, D., Nicanor-Juárez, L. E., Romero-Rizo, C. E. M., Farfán-García, E. D., & Soriano-Ursúa, M. A. (2023). Effects of boron-containing compounds on liposoluble hormone functions. Inorganics, 11(2), 84. https://doi.org/10.3390/inorganics11020084
  • Faccio, L., Da Silva, A. S., Tonin, A. A., França, R. T., Gressler, L. T., Copetti, M. M., … & Monteiro, S. G. (2013). Serum levels of LH, FSH, estradiol and progesterone in female rats experimentally infected by Trypanosoma evansi. Experimental Parasitology, 135(1), 110-115. https://doi.org/10.1016/j.exppara.2013.06.008
  • Bello, M., Guadarrama-García, C., Velasco-Silveyra, L. M., Farfán-García, E. D., & Soriano-Ursúa, M. A. (2018). Several effects of boron are induced by uncoupling steroid hormones from their transporters in blood. Medical Hypotheses, 118, 78-83. https://doi.org/10.1016/j.mehy.2018.06.024
  • Sheng, M. H. C., Taper, L. J., Veit, H., Thomas, E. A., Ritchey, S. J., & Lau, K. H. W. (2001). Dietary boron supplementation enhances the effects of estrogen on bone mineral balance in ovariectomized rats. Biological Trace Element Research, 81, 29-45. https://doi.org/10.1385/BTER:81:1:29
  • Duydu, Y., Başaran, N., Üstündağ, A., Aydın, S., Ündeğer, Ü., Ataman, … & Bolt, H. M. (2016). Is boric acid toxic to reproduction in humans? Assessment of the animal reproductive toxicity data and epidemiological study results. Current Drug Delivery, 13(3), 324-329. https://doi.org/10.2174/1567201812666151029101514
  • Ku, W. W., & Chapin, R. E. (1994). Mechanism of the testicular toxicity of boric acid in rats: In vivo and in vitro studies. Environmental Health Perspectives, 102(Suppl 7), 99-105. https://doi.org/10.1289/ehp.94102s799
  • Bolt, H. M., Başaran, N., & Duydu, Y. (2020). Effects of boron compounds on human reproduction. Archives of Toxicology, 94, 717-724. https://doi.org/10.1007/s00204-020-02700-x
  • Hadrup, N., Frederiksen, M., & Sharma, A. K. (2021). Toxicity of boric acid, borax and other boron containing compounds: A review. Regulatory Toxicology and Pharmacology, 121, 104873. https://doi.org/10.1016/j.yrtph.2021.104873
  • Özdemir, Ç., Arslan, M., Küçük, A., Yığman, Z., & Dursun, A. D. (2023). Therapeutic efficacy of boric acid treatment on brain tissue and cognitive functions in rats with experimental Alzheimer’s disease. Drug Design, Development and Therapy, 17, 1453-1462. https://doi.org/10.2147/DDDT.S405963
  • Luna, L. G. (1968). Manual of histologic staining methods of the Armed Forces Institute of Pathology (3rd ed.). McGraw-Hill Book Company.
  • Başeğmez, M., & Doğan, M. F. (2024). Effects of boric acid on oxidant-antioxidant, proinflammatory cytokine levels, and biochemical parameters in aged rats. Pamukkale Medical Journal, 17(2), 369-379. https://doi.org/10.31362/patd.1438593
  • Wang, Y., Zhao, Y., & Chen, X. (2008). Experimental study on the estrogen-like effect of boric acid. Biological Trace Element Research, 121(2), 160-170. https://doi.org/10.1007/s12011-007-8041-3
  • Endo, Y., Iijima, T., Yamakoshi, Y., Fukasawa, H., Miyaura, C., Inada, M., … & Itai, A. (2001). Potent estrogen agonists based on carborane as a hydrophobic skeletal structure: A new medicinal application of boron clusters. Chemistry & Biology, 8(4), 341-355. https://doi.org/10.1016/S1074-5521(01)00016-3
  • Sheng, M. H.-C., Taper, L. J., Veit, H., Qian, H., Ritchey, S. J., & Lau, K.-H. W. (2001). Dietary boron supplementation enhanced the action of estrogen, but not that of parathyroid hormone, to improve trabecular bone quality in ovariectomized rats. Biological Trace Element Research, 82, 109-123. https://doi.org/10.1385/BTER:82:1-3:109
  • Chapin, R. E., & Ku, W. W. (1994). The reproductive toxicity of boric acid. Environmental Health Perspectives, 102(Suppl. 7), 87-91. https://doi.org/10.2307/3431969
  • Pizzorno, L. (2015). Nothing boring about boron. Integrative Medicine: A Clinician's Journal, 14(4), 35-48.
  • Agoreyo, F., & Onwegbu, V. (2015). Quantitative evaluation of serum progesterone levels in the three trimesters of pregnancy in albino rat. Journal of Applied Sciences and Environmental Management, 19(1), 77-79. https://doi.org/10.4314/jasem.v19i1.10
  • Westwood, F. R. (2008). The female rat reproductive cycle: A practical histological guide to staging. Toxicologic Pathology, 36(3), 375-384. https://doi.org/10.1177/0192623308315665
  • Lovick, T. A., & Zangrossi Jr., H. (2021). Effect of estrous cycle on behavior of females in rodent tests of anxiety. Frontiers in Psychiatry, 12, 711065. https://doi.org/10.3389/fpsyt.2021.711065
  • Naghii, M. R., Mofid, M., Asgari, A. R., Hedayati, M., & Daneshpour, M. S. (2011). Comparative effects of daily and weekly boron supplementation on plasma steroid hormones and proinflammatory cytokines. Journal of Trace Elements in Medicine and Biology, 25(1), 54-58. https://doi.org/10.1016/j.jtemb.2010.10.001
  • Duydu, Y., Başaran, N., Aydın, S., Üstündağ, A., Yalçin, C. Ö., Anlar, H. G., … & Bolt, H. M. (2018). Evaluation of FSH, LH, testosterone levels and semen parameters in male boron workers under extreme exposure conditions. Archives of Toxicology, 92, 3051-3059. https://doi.org/10.1007/s00204-018-2296-7
  • Karaman, E., & Yavuz, A. (2024). Boric acid protects the uterus and fallopian tubes from cyclophosphamideınduced toxicity in a rat model. Pharmaceuticals, 17(12), 1716. https://doi.org/10.3390/ph17121716
  • Aydın, M., Çağlayan, N., Kara, Ö., & Kara, M. (2025). Protective effect of boric acid on ovarian damage caused by endotoxaemia. Journal of Obstetrics and Gynaecology Research, 51(8), e70055. https://doi.org/10.1111/jog.70055
  • Watson, A. T. D., Sutherland, V. L., Cunny, H., Miller-Pinsler, L., Furr, J., Hebert, C., … & McIntyre, B. S. (2020). Postnatal effects of gestational and lactational gavage exposure to boric acid in the developing Sprague Dawley rat. Toxicological Sciences, 176(1), 65-73. https://doi.org/10.1093/toxsci/kfaa061
  • Duydu, Y., Başaran, N., Üstündağ, A., Aydın, S., Yalçın, C. Ö., Anlar, H. … & Bolt, H. M. (2018). Birth weights of newborns and pregnancy outcomes of environmentally boron-exposed females in Turkey. Archives of Toxicology, 92, 2475-2485. https://doi.org/10.1007/s00204-018-2238-4
  • Büyükgüzel, E., Büyükgüzel, K., Snela, M., Erdem, M., Radtke, K., Ziemnicki, K., & Adamski, Z. (2013). Effect of boric acid on antioxidant enzyme activity, lipid peroxidation, and ultrastructure of mid-gut and fat body of Galleria mellonella. Cell Biology and Toxicology, 29, 117-129. https://doi.org/10.1007/s10565-013-9240-7
Toplam 31 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular İnorganik Kimya (Diğer)
Bölüm Araştırma Makalesi
Yazarlar

Mehmet Başeğmez 0000-0002-9994-1251

Nurcan Doğan 0009-0006-9287-3280

Hasan Hüseyin Demirel 0000-0002-4795-2266

Muhammed Fatih Doğan 0000-0003-4628-2771

Gönderilme Tarihi 9 Ağustos 2025
Kabul Tarihi 27 Ekim 2025
Yayımlanma Tarihi 31 Aralık 2025
Yayımlandığı Sayı Yıl 2025 Cilt: 10 Sayı: 4

Kaynak Göster

APA Başeğmez, M., Doğan, N., Demirel, H. H., Doğan, M. F. (2025). Effects of boric acid on reproductive hormones and utero-ovarian tissues in female rats: A dose-response study. Journal of Boron, 10(4), 150-155. https://doi.org/10.30728/boron.1761512