Research Article
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Eisenia foetida (Sav.) coelomic fluid protect human umbilical vein endothelial cells against metformin-induced cell toxicity

Year 2025, Issue: Online First

Elif Kale Bakır , Asuman Deveci Özkan , Özlem Aksoy , Yonca Yüzügüllü Karakuş

https://doi.org/10.23902/trkjnat.1598922

Abstract

The coelomic fluid of the red California earthworm Eisenia foetida (Sav.) includes a number of bioactive substances with antitumor and protective effects, thus making the fluid to also act as a defensive agent for the organism. Eisenia foetida coelomic fluid can be used as an alternative medication, for it is readily available and has few adverse effects. Metformin are widely used for managing type 2 diabetes mellitus by improving insulin sensitivity and reducing hepatic glucose production; however, therapeutic dose-related adverse effects have been reported. The present investigation aims to determine, for the first time, the protective effects of E. foetida coelomic fluid against possible metformin toxicity at the molecular and cellular levels. Metformin-induced cell toxicity was conducted following E. foetida coelomic fluid pre-treatment in Human Umbilical Vein Endothelial Cells (HUVEC). In addition to cell and nuclear morphology observation, a decrease in reactive oxygen species and apoptotic cell rate was determined. According to the obtained findings, the coelomic fluid of E. foetida preserved cell viability and morphology, reduced reactive oxygen species and apoptosis cell death, and enhanced anti-apoptotic mRNA expressions. When treating diseases, medical support and adjunct therapies should be taken into account. In this sense, our present preliminary in vitro findings showed that E. foetida coelomic fluid might has great additional treatment potential, and further molecular and animal studies to support this effect are needed.

Keywords

Guanidine Type-2 Diabetes California worm HUVEC Cell viability

Ethical Statement

Since the article does not contain any studies with human or animal subject, its approval to the ethics committee was not required.

References

  • 1. Abad, K., Kien, C. & Ganta, K. 2020. A Unique Case of Metformin-associated Severe Lactic Acidosis Without Preexisting Renal Disease: Perspectives on Prolonged Dialysis and Education for Prevention. Cureus, 12(4): e7564. https://doi.org/10.7759/cureus.7564
  • 2. Abutaleb, A. & Kottilil, S. 2020. Hepatitis A. Gastroenterology Clinics of North America, 49(2): 191-199. https://doi.org/10.1016/j.gtc.2020.01.002
  • 3. Adeva-Andany, M., López-Ojén, M., Funcasta-Calderón, R., Ameneiros-Rodríguez, E., Donapetry-García, C., Vila-Altesor, M. & Rodríguez-Seijas, J. 2014. Comprehensive review on lactate metabolism in human health. Michondrion, 17: 76-100. https://doi.org/10.1016/j.mi-.2014.05.007
  • 4. Bennis, Y., Bodeau, S., Batteux, B., Gras-Champel, V., Masmoudi, K., Maizel, J., De Broe, M. E., Lalau, J. D. & Lemaire-Hurtel, A. S. 2020. A Study of Associations Between Plasma Metformin Concentration, Lactic Acidosis, and Mortality in an Emergency Hospitalization Context. Critical Care Medicine, 48(12): e1194-e1202. https://doi.org/10.1097/CCM.0000000000004589
  • 5. Biyyani, R.S.R.S., Battula, S., Erhardt, C.A. & Korkor, K. 2009. Metformin-induced cholangiohepatitis. Case Reports, 2009: bcr0920080950. https://doi.org/10.1136/bcr.09.2008.0950
  • 6. Blough, B., Moreland, A. & Mora, A. 2015. Metformin-Induced Lactic Acidosis with Emphasis on the Anion Gap. Baylor University Medical Center Proceedings, 28(1): 31-33. https://doi.org/10.1080/08998280.2015.11929178
  • 7. Cone, C.J., Bachyrycz, A.M. & Murata, G.H. 2010. Hepaxicity associated with metformin therapy in treatment of type 2 diabetes mellitus with nonalcoholic fatty liver disease. The Annals of Pharmacotherapy, 44(10): 1655-1659. https://doi.org/10.1345/aph.1P099
  • 8. Crowley, L.C., Marfell, B.J., Scott, A.P. & Waterhouse, N.J. 2016. Quantitation of Apoptosis and Necrosis by Annexin V Binding, Propidium Iodide Uptake, and Flow Cytometry. Cold Spring Harbor Protocols, 2016(11): pdb.prot087288. https://doi.org/10.1101/pdb.prot087288
  • 9. Dajem, S., Ali, S., Abdelrady, O., Salahaldin, N., Soliman, A., Kamal, Y., Abdelazim, A., Mohamed, A., Morsy, K., Mohamed, A. & Fahmy, S. 2020. Allolobophora caliginosa coelomic fluid ameliorates gentamicin-induced hepatorenal toxicity in rats. Asian Pacific Journal of Tropical Biomedicine, 10(9): 411. https://doi.org/10.4103/2221-1691.290132
  • 10. DeFronzo, R., Fleming, G.A., Chen, K. & Bicsak, T.A. 2016. Metformin-associated lactic acidosis: Current perspectives on causes and risk. Metabolism: Clinical and Experimental, 65(2): 20-29. https://doi.org/10.1016/j.metabol.2015.10.014
  • 11. Deng, Z., Yin, J., Luo, W., Kotian, R.N., Gao, S., Yi, Z., Xiao, W., Li, W. & Li, Y. 2018. The effect of earthworm extract on promoting skin wound healing. Bioscience Reports, 38(2): BSR20171366. https://doi.org/10.1042/BSR20171366
  • 12. Deveci Özkan, A., Alimudin, J., Kilciler, Y., Yuksel, B., Aksoy, O. & Betts, Z. 2023. In vitro chemo-protective effect of Eisenia foetida coelomic fluid against histone deacetylase inhibitor-induced oxidative toxicity in breast cancer cells. International Journal of Environmental Health Research, 33(12): 1728-1737. https://doi.org/10.1080/09603123.2022.2120970
  • 13. Fontaine, E. 2018. Metformin-Induced Mitochondrial Complex I Inhibition: Facts, Uncertainties, and Consequences. Frontiers in Endocrinology, 9: 753. https://doi.org/10.3389/fendo.2018.00753
  • 14. Ghosh, P. 2017. The stress polarity pathway: AMPK ’GIV’-es protection against metabolic insults. Aging, 9(2): 303-314. https://doi.org/10.18632/aging.101179
  • 15. Grdisa, M., Popovic, M. & Hrzenjak, T. 2001. Glycolipoprotein extract (G-90) from earthworm Eisenia foetida exerts some antioxidative activity. Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology, 128(4): 821-825. https://doi.org/10.1016/s1095-6433(00)00323-8
  • 16. Harrigan, R.A., Nathan, M.S. & Beattie, P. 2001. Oral agents for the treatment of type 2 diabetes mellitus: Pharmacology, toxicity, and treatment. Annals of Emergency Medicine, 38(1): 68-78. https://doi.org/10.1067/mem.2001.114314
  • 17. Hasanvand, A., Abbaszadeh, A., Darabi, S., Nazari, A., Gholami, M. & Kharazmkia, A. 2016. Evaluation of selenium on kidney function following ischemic injury in rats; protective effects and antioxidant activity. Journal of Renal Injury Prevention, 6(2): 93-98. https://doi.org/10.15171/jrip.2017.18
  • 18. Heredia Rivera, B., Rodríguez, M.G., Rodríguez-Heredia, M., Rodríguez-Heredia, B., Barois, I. & González Segovia, R. 2020. Characterisation by Excitation-Emission Matrix Fluorescence Spectroscopy of Pigments in Mucus Secreted of Earthworm Eisenia foetida Exposed to Lead. Journal of Fluorescence, 30(3): 725-733. https://doi.org/10.1007/s10895-020-02533-y
  • 19. Houston, R., Sekine, Y., Larsen, M.B., Murakami, K., Mullett, S.J., Wendell, S.G., Narendra, D.P., Chen, B.B. & Sekine, S. 2021. Discovery of bactericides as an acute michondrial membrane damage inducer. Molecular Biology of The Cell, 32(21): ar32. https://doi.org/10.1091/mbc.E21-04-0191
  • 20. Hua, Z., Wang, Y.-H., Cao, H.-W., Pu, L.-J. & Cui, Y.-D. 2011. Purification of a protein from coelomic fluid of the earthworm Eisenia foetida and evaluation of its hemolytic, antibacterial, and antitumor activities. Pharmaceutical Biology, 49(3): 269-275. https://doi.org/10.3109/13880209.2010.508498
  • 21. Kilciler, Y., Deveci Ozkan, A. & Betts, Z. 2022. Protective effect of Eisenia foetida coelomic fluid against oxidative damage in human endothelial cells. Toxicological & Environmental Chemistry, 104(2): 307-320. https://doi.org/10.1080/02772248.2022.2137165
  • 22. Kutoh, E. 2005. Possible metformin-induced hepatotoxicity. The American Journal of Geriatric Pharmacotherapy, 3(4): 270-273.
  • 23. LaMoia, T. E. & Shulman, G. I. 2021. Cellular and Molecular Mechanisms of Metformin Action. Endocrine Reviews, 42(1): 77-96. https://doi.org/10.1210/endrev/bnaa023
  • 24. Lin, Z., Zhen, Z., Ren, L., Yang, J., Luo, C., Zhong, L., Hu, H., Liang, Y., Li, Y. & Zhang, D. 2018. Effects of two ecological earthworm species on atrazine degradation performance and bacterial community structure in red soil. Chemosphere, 196: 467-475. https://doi.org/10.1016/j.chemosphere.2017.12.177
  • 25. Nammour, F.E., Fayad, N.F. & Peikin, S.R. 2003. Metformin-Induced Cholestatic Hepatitis. Endocrine Practice, 9(4): 307-309. https://doi.org/10.4158/EP.9.4.307
  • 26. Ozkan, A.D., Eskiler, G.G., Sarihan, M., Kazan, N., Aksoy, O., Yuksel, B. & Betts, Z. 2022. Anticancer Properties of Eisenia Foetida Proteins in Prostate Cancer Cells In Vitro. International Journal of Peptide Research and Therapeutics, 28(4): 119. https://doi.org/10.1007/s10989-022-10428-8
  • 27. Park, H.J., Zhang, Y., Georgescu, S.P., Johnson, K L., Kong, D. & Galper, J.B. 2006. Human umbilical vein endothelial cells and human dermal microvascular endothelial cells offer new insights into the relationship between lipid metabolism and angiogenesis. Stem Cell Reviews, 2(2): 93-102. https://doi.org/10.1007/s12015-006-0015-x
  • 28. Pfeiffer, A.F. & Klein, H.H. 2014. The treatment of type 2 diabetes. Deutsches Arzteblatt International, 111(5): 69-82. https://doi.org/10.3238/arztebl.2014.0069
  • 29. Rafieian-Kopaei, M., Baradaran, A., Merrikhi, A., Nematbakhsh, M., Madihi, Y. & Nasri, H. 2013. Efficacy of Co-administration of Garlic Extract and Metformin for Prevention of Gentamicin-Renal toxicity in Wistar Rats: A Biochemical Study. International Journal of Preventive Medicine, 4(3): 258-264.
  • 30. Romero, R., Erez, O., Hüttemann, M., Maymon, E., Panaitescu, B., Conde-Agudelo, A., Pacora, P., Yoon, B. H. & Grossman, L. I. 2017. Metformin, the aspirin of the 21st century: its role in gestational diabetes mellitus, prevention of preeclampsia and cancer, and the promotion of longevity. American Journal of Obstetrics and Gynecology, 217(3): 282-302. https://doi.org/10.1016/j.ajog.2017.06.003
  • 31. Shi, G., Wang, Y., Yang, J., Liu, T., Luo, F., Jin, G., Ma, Y. & Zhang, Y. 2021. Effect of Cryptotanshinone on Measures of Rat Cardiomyocyte Oxidative Stress and Gene Activation Associated with Apoptosis. Cardiorenal Medicine, 11(1): 18-26. https://doi.org/10.1159/000507184
  • 32. Stanton, R.C. 2015. Metformin Use in Type 2 Diabetes Mellitus With CKD: Is It Time to Liberalize Dosing Recommendations? American Journal of Kidney Diseases, 66(2): 193-195. https://doi.org/10.1053/j.ajkd.2015.04.001
  • 33. Vargas, F. da S., Soares, D.G., Ribeiro, A.P.D., Hebling, J. & De Souza Costa, C.A. 2014. Protective Effect of Alpha-tocopherol Isomer from Vitamin E against the H2O2 Induced toxicity on Dental Pulp Cells. BioMed Research International, 2014: 1-5. https://doi.org/10.1155/2014/895049
  • 34. Vial, G., Detaille, D. & Guigas, B. 2019. Role of Mitochondria in the Mechanism(s) of Action of Metformin. Frontiers in Endocrinology, 10: 294. https://doi.org/10.3389/fendo.2019.00294
  • 35. Wang, G.S. & Hoyte, C. 2019. Review of Biguanide (Metformin) toxicity. Journal of Intensive Care Medicine, 34(11-12): 863-876. https://doi.org/10.1177/0885066618793385

Year 2025, Issue: Online First

Elif Kale Bakır , Asuman Deveci Özkan , Özlem Aksoy , Yonca Yüzügüllü Karakuş

https://doi.org/10.23902/trkjnat.1598922

Abstract

Kırmızı Kaliforniya solucanı Eisenia foetida'nın (Sav.) sölomik sıvısı, antitümör ve koruyucu etkilere sahip bir dizi biyoaktif maddeyi içerdiğinden, bu sıvının aynı zamanda organizma için bir savunma maddesi olarak da işlev görmesi sağlanmaktadır. Eisenia foetida sölomik sıvısı, kolayca bulunabilmesi ve yan etkilerinin az olması nedeniyle alternatif bir ilaç olarak kullanılabilir. Metformin, insülin duyarlılığını artırarak ve hepatik glukoz üretimini azaltarak tip 2 diyabetin tedavisinde yaygın olarak kullanılmaktadır; ancak terapötik doza bağlı yan etkiler bildirilmiştir. Bu araştırmanın amacı, E. foetida sölomik sıvısının olası metformin toksisitesine karşı moleküler ve hücresel düzeyde koruyucu etkilerini ilk kez belirlemektir. Metformin kaynaklı hücre toksisitesi, E. foetida sölomik sıvısı ön muamelesinin ardından gerçekleştirildi. Hücre ve nükleer morfoloji gözlemine ek olarak, reaktif oksijen türleri ve hücre ölümü üzerindeki koruyucu etkisi belirlendi. Elde edilen bulgulara göre, E. foetida sölomik sıvısı hücre canlılığını ve morfolojisini korudu, reaktif oksijen türlerini ve apoptotik hücre ölümünü azalttı ve anti-apoptotik mRNA ekspresyonlarını arttırdı. Hastalıkların tedavisi, destekleyici bakım ve yardımcı tedavilerin dikkate alınmasını içermelidir. Bu anlamda, bu in vitro ön bulgularımız E. foetida sölomik sıvısının büyük yardımcı tedavi potansiyeline sahip olduğunu gösterdi ve bu etkiyi desteklemek için daha fazla moleküler ve hayvan çalışmasına ihtiyaç vardır.

References

  • 1. Abad, K., Kien, C. & Ganta, K. 2020. A Unique Case of Metformin-associated Severe Lactic Acidosis Without Preexisting Renal Disease: Perspectives on Prolonged Dialysis and Education for Prevention. Cureus, 12(4): e7564. https://doi.org/10.7759/cureus.7564
  • 2. Abutaleb, A. & Kottilil, S. 2020. Hepatitis A. Gastroenterology Clinics of North America, 49(2): 191-199. https://doi.org/10.1016/j.gtc.2020.01.002
  • 3. Adeva-Andany, M., López-Ojén, M., Funcasta-Calderón, R., Ameneiros-Rodríguez, E., Donapetry-García, C., Vila-Altesor, M. & Rodríguez-Seijas, J. 2014. Comprehensive review on lactate metabolism in human health. Michondrion, 17: 76-100. https://doi.org/10.1016/j.mi-.2014.05.007
  • 4. Bennis, Y., Bodeau, S., Batteux, B., Gras-Champel, V., Masmoudi, K., Maizel, J., De Broe, M. E., Lalau, J. D. & Lemaire-Hurtel, A. S. 2020. A Study of Associations Between Plasma Metformin Concentration, Lactic Acidosis, and Mortality in an Emergency Hospitalization Context. Critical Care Medicine, 48(12): e1194-e1202. https://doi.org/10.1097/CCM.0000000000004589
  • 5. Biyyani, R.S.R.S., Battula, S., Erhardt, C.A. & Korkor, K. 2009. Metformin-induced cholangiohepatitis. Case Reports, 2009: bcr0920080950. https://doi.org/10.1136/bcr.09.2008.0950
  • 6. Blough, B., Moreland, A. & Mora, A. 2015. Metformin-Induced Lactic Acidosis with Emphasis on the Anion Gap. Baylor University Medical Center Proceedings, 28(1): 31-33. https://doi.org/10.1080/08998280.2015.11929178
  • 7. Cone, C.J., Bachyrycz, A.M. & Murata, G.H. 2010. Hepaxicity associated with metformin therapy in treatment of type 2 diabetes mellitus with nonalcoholic fatty liver disease. The Annals of Pharmacotherapy, 44(10): 1655-1659. https://doi.org/10.1345/aph.1P099
  • 8. Crowley, L.C., Marfell, B.J., Scott, A.P. & Waterhouse, N.J. 2016. Quantitation of Apoptosis and Necrosis by Annexin V Binding, Propidium Iodide Uptake, and Flow Cytometry. Cold Spring Harbor Protocols, 2016(11): pdb.prot087288. https://doi.org/10.1101/pdb.prot087288
  • 9. Dajem, S., Ali, S., Abdelrady, O., Salahaldin, N., Soliman, A., Kamal, Y., Abdelazim, A., Mohamed, A., Morsy, K., Mohamed, A. & Fahmy, S. 2020. Allolobophora caliginosa coelomic fluid ameliorates gentamicin-induced hepatorenal toxicity in rats. Asian Pacific Journal of Tropical Biomedicine, 10(9): 411. https://doi.org/10.4103/2221-1691.290132
  • 10. DeFronzo, R., Fleming, G.A., Chen, K. & Bicsak, T.A. 2016. Metformin-associated lactic acidosis: Current perspectives on causes and risk. Metabolism: Clinical and Experimental, 65(2): 20-29. https://doi.org/10.1016/j.metabol.2015.10.014
  • 11. Deng, Z., Yin, J., Luo, W., Kotian, R.N., Gao, S., Yi, Z., Xiao, W., Li, W. & Li, Y. 2018. The effect of earthworm extract on promoting skin wound healing. Bioscience Reports, 38(2): BSR20171366. https://doi.org/10.1042/BSR20171366
  • 12. Deveci Özkan, A., Alimudin, J., Kilciler, Y., Yuksel, B., Aksoy, O. & Betts, Z. 2023. In vitro chemo-protective effect of Eisenia foetida coelomic fluid against histone deacetylase inhibitor-induced oxidative toxicity in breast cancer cells. International Journal of Environmental Health Research, 33(12): 1728-1737. https://doi.org/10.1080/09603123.2022.2120970
  • 13. Fontaine, E. 2018. Metformin-Induced Mitochondrial Complex I Inhibition: Facts, Uncertainties, and Consequences. Frontiers in Endocrinology, 9: 753. https://doi.org/10.3389/fendo.2018.00753
  • 14. Ghosh, P. 2017. The stress polarity pathway: AMPK ’GIV’-es protection against metabolic insults. Aging, 9(2): 303-314. https://doi.org/10.18632/aging.101179
  • 15. Grdisa, M., Popovic, M. & Hrzenjak, T. 2001. Glycolipoprotein extract (G-90) from earthworm Eisenia foetida exerts some antioxidative activity. Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology, 128(4): 821-825. https://doi.org/10.1016/s1095-6433(00)00323-8
  • 16. Harrigan, R.A., Nathan, M.S. & Beattie, P. 2001. Oral agents for the treatment of type 2 diabetes mellitus: Pharmacology, toxicity, and treatment. Annals of Emergency Medicine, 38(1): 68-78. https://doi.org/10.1067/mem.2001.114314
  • 17. Hasanvand, A., Abbaszadeh, A., Darabi, S., Nazari, A., Gholami, M. & Kharazmkia, A. 2016. Evaluation of selenium on kidney function following ischemic injury in rats; protective effects and antioxidant activity. Journal of Renal Injury Prevention, 6(2): 93-98. https://doi.org/10.15171/jrip.2017.18
  • 18. Heredia Rivera, B., Rodríguez, M.G., Rodríguez-Heredia, M., Rodríguez-Heredia, B., Barois, I. & González Segovia, R. 2020. Characterisation by Excitation-Emission Matrix Fluorescence Spectroscopy of Pigments in Mucus Secreted of Earthworm Eisenia foetida Exposed to Lead. Journal of Fluorescence, 30(3): 725-733. https://doi.org/10.1007/s10895-020-02533-y
  • 19. Houston, R., Sekine, Y., Larsen, M.B., Murakami, K., Mullett, S.J., Wendell, S.G., Narendra, D.P., Chen, B.B. & Sekine, S. 2021. Discovery of bactericides as an acute michondrial membrane damage inducer. Molecular Biology of The Cell, 32(21): ar32. https://doi.org/10.1091/mbc.E21-04-0191
  • 20. Hua, Z., Wang, Y.-H., Cao, H.-W., Pu, L.-J. & Cui, Y.-D. 2011. Purification of a protein from coelomic fluid of the earthworm Eisenia foetida and evaluation of its hemolytic, antibacterial, and antitumor activities. Pharmaceutical Biology, 49(3): 269-275. https://doi.org/10.3109/13880209.2010.508498
  • 21. Kilciler, Y., Deveci Ozkan, A. & Betts, Z. 2022. Protective effect of Eisenia foetida coelomic fluid against oxidative damage in human endothelial cells. Toxicological & Environmental Chemistry, 104(2): 307-320. https://doi.org/10.1080/02772248.2022.2137165
  • 22. Kutoh, E. 2005. Possible metformin-induced hepatotoxicity. The American Journal of Geriatric Pharmacotherapy, 3(4): 270-273.
  • 23. LaMoia, T. E. & Shulman, G. I. 2021. Cellular and Molecular Mechanisms of Metformin Action. Endocrine Reviews, 42(1): 77-96. https://doi.org/10.1210/endrev/bnaa023
  • 24. Lin, Z., Zhen, Z., Ren, L., Yang, J., Luo, C., Zhong, L., Hu, H., Liang, Y., Li, Y. & Zhang, D. 2018. Effects of two ecological earthworm species on atrazine degradation performance and bacterial community structure in red soil. Chemosphere, 196: 467-475. https://doi.org/10.1016/j.chemosphere.2017.12.177
  • 25. Nammour, F.E., Fayad, N.F. & Peikin, S.R. 2003. Metformin-Induced Cholestatic Hepatitis. Endocrine Practice, 9(4): 307-309. https://doi.org/10.4158/EP.9.4.307
  • 26. Ozkan, A.D., Eskiler, G.G., Sarihan, M., Kazan, N., Aksoy, O., Yuksel, B. & Betts, Z. 2022. Anticancer Properties of Eisenia Foetida Proteins in Prostate Cancer Cells In Vitro. International Journal of Peptide Research and Therapeutics, 28(4): 119. https://doi.org/10.1007/s10989-022-10428-8
  • 27. Park, H.J., Zhang, Y., Georgescu, S.P., Johnson, K L., Kong, D. & Galper, J.B. 2006. Human umbilical vein endothelial cells and human dermal microvascular endothelial cells offer new insights into the relationship between lipid metabolism and angiogenesis. Stem Cell Reviews, 2(2): 93-102. https://doi.org/10.1007/s12015-006-0015-x
  • 28. Pfeiffer, A.F. & Klein, H.H. 2014. The treatment of type 2 diabetes. Deutsches Arzteblatt International, 111(5): 69-82. https://doi.org/10.3238/arztebl.2014.0069
  • 29. Rafieian-Kopaei, M., Baradaran, A., Merrikhi, A., Nematbakhsh, M., Madihi, Y. & Nasri, H. 2013. Efficacy of Co-administration of Garlic Extract and Metformin for Prevention of Gentamicin-Renal toxicity in Wistar Rats: A Biochemical Study. International Journal of Preventive Medicine, 4(3): 258-264.
  • 30. Romero, R., Erez, O., Hüttemann, M., Maymon, E., Panaitescu, B., Conde-Agudelo, A., Pacora, P., Yoon, B. H. & Grossman, L. I. 2017. Metformin, the aspirin of the 21st century: its role in gestational diabetes mellitus, prevention of preeclampsia and cancer, and the promotion of longevity. American Journal of Obstetrics and Gynecology, 217(3): 282-302. https://doi.org/10.1016/j.ajog.2017.06.003
  • 31. Shi, G., Wang, Y., Yang, J., Liu, T., Luo, F., Jin, G., Ma, Y. & Zhang, Y. 2021. Effect of Cryptotanshinone on Measures of Rat Cardiomyocyte Oxidative Stress and Gene Activation Associated with Apoptosis. Cardiorenal Medicine, 11(1): 18-26. https://doi.org/10.1159/000507184
  • 32. Stanton, R.C. 2015. Metformin Use in Type 2 Diabetes Mellitus With CKD: Is It Time to Liberalize Dosing Recommendations? American Journal of Kidney Diseases, 66(2): 193-195. https://doi.org/10.1053/j.ajkd.2015.04.001
  • 33. Vargas, F. da S., Soares, D.G., Ribeiro, A.P.D., Hebling, J. & De Souza Costa, C.A. 2014. Protective Effect of Alpha-tocopherol Isomer from Vitamin E against the H2O2 Induced toxicity on Dental Pulp Cells. BioMed Research International, 2014: 1-5. https://doi.org/10.1155/2014/895049
  • 34. Vial, G., Detaille, D. & Guigas, B. 2019. Role of Mitochondria in the Mechanism(s) of Action of Metformin. Frontiers in Endocrinology, 10: 294. https://doi.org/10.3389/fendo.2019.00294
  • 35. Wang, G.S. & Hoyte, C. 2019. Review of Biguanide (Metformin) toxicity. Journal of Intensive Care Medicine, 34(11-12): 863-876. https://doi.org/10.1177/0885066618793385
There are 35 citations in total.

Details

Primary Language English
Subjects Cell Development, Proliferation and Death, Gene Expression, Toxicology, Proteins and Peptides
Journal Section Research Article/Araştırma Makalesi
Authors

Elif Kale Bakır 0000-0002-4266-9517

Asuman Deveci Özkan 0000-0002-3248-4279

Özlem Aksoy 0000-0003-0969-5171

Yonca Yüzügüllü Karakuş 0000-0003-0286-8711

Early Pub Date March 1, 2025
Publication Date
Submission Date December 9, 2024
Acceptance Date February 14, 2025
Published in Issue Year 2025 Issue: Online First

Cite

APA Kale Bakır, E., Deveci Özkan, A., Aksoy, Ö., Yüzügüllü Karakuş, Y. (2025). Eisenia foetida (Sav.) coelomic fluid protect human umbilical vein endothelial cells against metformin-induced cell toxicity. Trakya University Journal of Natural Sciences(Online First). https://doi.org/10.23902/trkjnat.1598922
AMA Kale Bakır E, Deveci Özkan A, Aksoy Ö, Yüzügüllü Karakuş Y. Eisenia foetida (Sav.) coelomic fluid protect human umbilical vein endothelial cells against metformin-induced cell toxicity. Trakya Univ J Nat Sci. March 2025;(Online First). doi:10.23902/trkjnat.1598922
Chicago Kale Bakır, Elif, Asuman Deveci Özkan, Özlem Aksoy, and Yonca Yüzügüllü Karakuş. “Eisenia Foetida (Sav.) Coelomic Fluid Protect Human Umbilical Vein Endothelial Cells Against Metformin-Induced Cell Toxicity”. Trakya University Journal of Natural Sciences, no. Online First (March 2025). https://doi.org/10.23902/trkjnat.1598922.
EndNote Kale Bakır E, Deveci Özkan A, Aksoy Ö, Yüzügüllü Karakuş Y (March 1, 2025) Eisenia foetida (Sav.) coelomic fluid protect human umbilical vein endothelial cells against metformin-induced cell toxicity. Trakya University Journal of Natural Sciences Online First
IEEE E. Kale Bakır, A. Deveci Özkan, Ö. Aksoy, and Y. Yüzügüllü Karakuş, “Eisenia foetida (Sav.) coelomic fluid protect human umbilical vein endothelial cells against metformin-induced cell toxicity”, Trakya Univ J Nat Sci, no. Online First, March 2025, doi: 10.23902/trkjnat.1598922.
ISNAD Kale Bakır, Elif et al. “Eisenia Foetida (Sav.) Coelomic Fluid Protect Human Umbilical Vein Endothelial Cells Against Metformin-Induced Cell Toxicity”. Trakya University Journal of Natural Sciences Online First (March 2025). https://doi.org/10.23902/trkjnat.1598922.
JAMA Kale Bakır E, Deveci Özkan A, Aksoy Ö, Yüzügüllü Karakuş Y. Eisenia foetida (Sav.) coelomic fluid protect human umbilical vein endothelial cells against metformin-induced cell toxicity. Trakya Univ J Nat Sci. 2025. doi:10.23902/trkjnat.1598922.
MLA Kale Bakır, Elif et al. “Eisenia Foetida (Sav.) Coelomic Fluid Protect Human Umbilical Vein Endothelial Cells Against Metformin-Induced Cell Toxicity”. Trakya University Journal of Natural Sciences, no. Online First, 2025, doi:10.23902/trkjnat.1598922.
Vancouver Kale Bakır E, Deveci Özkan A, Aksoy Ö, Yüzügüllü Karakuş Y. Eisenia foetida (Sav.) coelomic fluid protect human umbilical vein endothelial cells against metformin-induced cell toxicity. Trakya Univ J Nat Sci. 2025(Online First).

You can reach the journal's archive between the years of 2000-2011 via https://dergipark.org.tr/en/pub/trakyafbd/archive (Trakya University Journal of Natural Sciences (=Trakya University Journal of Science)


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