Research Article
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Year 2021, , 25 - 36, 01.01.2021
https://doi.org/10.15671/hjbc.680564

Abstract

Supporting Institution

Yok

Project Number

Yok

Thanks

Yok

References

  • 1. M. DellaGreca, M. Brigante, M. Isidori, A. Nardelli, L. Previtera, M. Rubino, F. Temussi, Phototransformation and ecotoxicity of the drug Naproxen-Na, Environ. Chem. Lett., 1 (2003) 237-241.
  • 2. R. Runkel, M. Chaplin, G. Boost, E. Segre, E. Forchielli, Absorption, distribution, metabolism, and excretion of naproxen in various laboratory animals and human subjects, J. Pharm. Sci., 61 (1972) 703-708.
  • 3. J.V. Andersen, S.H. Hansen, Simultaneous quantitative determination of naproxen, its metabolite 6-Odesmethylnaproxen and their five conjugates in plasma and urine samples by highperformance liquid chromatography on dynamically modified silica, J. Chromatogr., 10 (1992) 325-33.
  • 4. J.O. Miners, S. Coulter, R.H. Tukey, M.E. Veronese, D.J. Birkett, Cytochromes P450, 1A2, and 2C9 are responsible for the human hepatic O-demethylation of R-and S-naproxen, Biomed. PharmacothEr., 51 (1996) 1003-1008.
  • 5. D.F. Zhong, L. Sun, L. Liu, H.H. Huang, Microbial transformation of naproxen by Cunninghamella species, Acta Pharmacol. Sin., 24 (2003) 442-447.
  • 6. N.M. Davies, K.E. Anderson, Clinical pharmacokinetics of naproxen, Clin. Pharmacokinet., 32 (1997) 268-293.
  • 7. T. Tracy, C. Marra, S. Wrighton, F. Gonzalez, K. Korzekwa, Involvement of multiple cytochrome P450 isoforms in naproxen O-demethylation, Eur. J. Clin. Pharmacol., 52 (1997) 293-298.
  • 8. K. Fent, A. A. Weston, D. Caminada, Erratum to “Ecotoxicology of human pharmaceuticals”[Aquatic Toxicology 76 (2006) 122–159], Aquat. Toxicol., 78 (2006a) 207.
  • 9. D. Domaradzka, U. Guzik, D. Wojcieszyńska, Biodegradation and biotransformation of polycyclic non-steroidal anti-inflammatory drugs, Rev. Environ. Sci. Biotechnol., 14 (2015) 229-239.
  • 10. H. Hühnerfuss, S. Selke, M. Scheurell, M.R. Shah, S. Nadeem, The drug naproxen and its transformation products as an example for emerging environmental pollutants, Organohalog. Compd., 72 (2010) 467-470.
  • 11. L.D. Buckberry, Cytotoxicity Testing Using Cell Lines, Animal Cell Biotechnology, Humana Press, Totowa, NJ, 1999.
  • 12. M. Isidori, M. Lavorgna, A. Nardelli, A. Parrella, L. Previtera, M. Rubino, Ecotoxicity of naproxen and its phototransformation products, Sci. Total. Environ., 348 (2005) 93-101.
  • 13. F.A. Alherz, D.A. Almarghalani, N.A. Hussein, K. Kurogi, M.C. Liu, A reappraisal of the 6-O-desmethylnaproxen-sulfating activity of the human cytosolic sulfotransferases, Can. J. Physiol. Pharmacol., 95 (2017) 647-651.
  • 14. XXXXXXXXXXXXXXX
  • 15. I. Correia, R. Arantes-Rodrigues, R. Pinto-Leite, I. Gaivão, Effects of naproxen on cell proliferation and genotoxicity in MG-63 osteosarcoma cell line, J. Toxicol. Env. Heal. A, 77 (2014) 916-923.
  • 16. B.I. Cohen, M.K. Pagnillo, B.L. Musikant, A.S. Deutsch, An in vitro study of the cytotoxicity of two root canal sealers, J. Endod., 26 (2000) 228-229.
  • 17. M. Akyol, Z. Akın Polat, S. Özçelik, Ö. Kaya, The effects of strontium chloride on viability of mouse connective tissue fibroblast cells, C.M.J., 35 (2013) 33-38.
  • 18. J. Carmichael, W.G. DeGraff, A.F. Gazdar, J.D. Minna, J.B. Mitchell, Evaluation of a tetrazolium-based semiautomated colorimetric assay: assessment of chemosensitivity testing, Cancer Res., 47 (1987) 936-942.
  • 19. S. Mohan, A. Bustamam, S. Ibrahim, A.S. Al-Zubairi, M. Aspollah, R. Abdullah, M.M. Elhassan, In vitro ultramorphological assessment of apoptosis on CEMss induced by linoleic acid-rich fraction from Typhonium flagelliforme tuber, Evid. Based Complement. Alternat. Med., (2011) 2011.
  • 20. A. Wahab, S. Ibrahim, A.B. Abdul, A.S. Alzubairi, M. Mohamed Elhassan, S.Mohan, In vitro ultramorphological assessment of apoptosis induced by zerumbone on (HeLa), BioMed. Res. Int., (2009) 2009.
  • 21. G. Tan, M. Kaya, A. Tevlek, I. Sargin, T. Baran, Antitumor activity of chitosan from mayfly with comparison to commercially available low, medium and high molecular weight chitosans, In Vitro Cell. Dev. Biol. Anim., 54 (2018) 366-374.
  • 22. E. Marco-Urrea, M. Pérez-Trujillo, P. Blánquez, T. Vicent, G.Caminal, Biodegradation of the analgesic naproxen by Trametes versicolor and identification of intermediates using HPLC-DAD-MS and NMR, Bioresour. Technol., 101 (2010) 2159-2166.
  • 23. E. Ricciotti, G.A. FitzGerald, Prostaglandins and inflammation, Arterioscler. Thromb. Vasc. Biol., 31 (2011) 986-1000.
  • 24. C.E. Smith, S. Soti, T.A. Jones, A. Nakagawa, D. Xue, H. Yin, Non-steroidal anti-inflammatory drugs are caspase inhibitors, Cell Chem. Biol., 24 (2017) 281-292. 25. K. Fent, A.A. Weston, D. Caminada, Ecotoxicology of human pharmaceuticals, Aquat. Toxicol., 76 (2006b) 122-159.
  • 26. C. Carlsson, A.K. Johansson, G. Alvan, K. Bergman, T. Kühler, Are pharmaceuticals potent environmental pollutants?: Part I: Environmental risk assessments of selected active pharmaceutical ingredients, Sci. Total Environ., 364 (2006) 67-87.
  • 27. S. Selke, M. Scheurell, M.R. Shah, H. Hühnerfuss, Identification and enantioselective gas chromatographic mass-spectrometric separation of O-desmethylnaproxen, the main metabolite of the drug naproxen, as a new environmental contaminant, J. Chromatogr. A., 1217 (2010) 419-423.
  • 28. G. Lucena,C. Reyes-Botella, O. García-Martínez, J. Ramos-Torrecillas, E.D.L., Bertos, C. Ruiz, Effect of NSAIDs on the aminopeptidase activity of cultured human osteoblasts, Mol. Cell. Endocrinol., 426 (2016) 146-154.
  • 29. E. De Luna-Bertos, J. Ramos-Torrecillas, O. García-Martínez, A. Guildford, M. Santin, C. Ruiz, Therapeutic doses of nonsteroidal anti-inflammatory drugs inhibit osteosarcoma MG-63 osteoblast-like cells maturation, viability, and biomineralization potential, Sci. World J., (2013) 2013.
  • 30. H. Axelsson, C. Lönnroth, M. Andersson, K. Lundholm, Mechanisms behind COX-1 and COX-2 inhibition of tumor growth in vivo, Int. J. Oncol., 37 (2010) 1143.
  • 31. L. Díaz‐Rodríguez, O. García‐Martínez, M. Arroyo‐Morales, C. Reyes‐Botella, C. Ruiz, Antigenic Phenotype and Phagocytic Capacity of MG‐63 Osteosarcoma Line, Ann. N. Y. Acad. Sci., 1173 (2009) E46-E54.
  • 32. L. Díaz-Rodríguez, O. García-Martínez, E. De Luna-Bertos, J. Ramos-Torrecillas, C. Ruiz, Effect of ibuprofen on proliferation, differentiation, antigenic expression, and phagocytic capacity of osteoblasts, J. Bone Miner. Metab., 30 (2012a) 554-560.
  • 33. L. Díaz-Rodríguez, O. García-Martínez, M.A. Morales, L. Rodríguez-Pérez, B. Rubio-Ruiz, C. Ruiz, Effects of indomethacin, nimesulide, and diclofenac on human MG-63 osteosarcoma cell line, Biol. Res. Nurs., 14 (2012b) 98-107.
  • 34. E. De Luna-Bertos, J. Ramos-Torrecillas, O. García-Martínez, L. Diaz-Rodriguez, C. Ruiz, Effect of aspirin on cell growth of human MG-63 osteosarcoma line, Sci. World J., (2012) 2012.
  • 35. A. Aresta, T. Carbonara, F. Palmisano, C.G. Zambonin, Profiling urinary metabolites of naproxen by liquid chromatography–electrospray mass spectrometry, J. Pharm. Biomed. Anal., 41 (2006) 1312-1316.

In Vitro Evaluation Of Naproxen Metabolite, O-Desmethylnaproxen On A Mouse Connective Tissue Fibroblast Cells

Year 2021, , 25 - 36, 01.01.2021
https://doi.org/10.15671/hjbc.680564

Abstract

The aim of this in vitro study was assessment of the cytotoxic level of 6-O-desmethylnaproxen. A mouse connective tissue fibroblast cell line, L929 was exposed to naproxen and 6-O-desmethylnaproxen in different concentrations for 24- and 48- hours. Cell viability was tested by MTT, while apoptosis was determined by AO/PI double staining method. The control group was free from any agent (DMEM only) and accepted as 100% cell viability. The IC50 results indicated that the inhibition of 50% cell viability was resulted by the highest concentration of 6-O-desmethylnaproxen (0.7 µg/mL) while none of naproxen concentration was caused 50% cell dead. Consequently, to avoid the unacceptable side effects of naproxen metabolites that evacuated by urine; further studies should be conducted to determine the accumulation of naproxen metabolites.

Project Number

Yok

References

  • 1. M. DellaGreca, M. Brigante, M. Isidori, A. Nardelli, L. Previtera, M. Rubino, F. Temussi, Phototransformation and ecotoxicity of the drug Naproxen-Na, Environ. Chem. Lett., 1 (2003) 237-241.
  • 2. R. Runkel, M. Chaplin, G. Boost, E. Segre, E. Forchielli, Absorption, distribution, metabolism, and excretion of naproxen in various laboratory animals and human subjects, J. Pharm. Sci., 61 (1972) 703-708.
  • 3. J.V. Andersen, S.H. Hansen, Simultaneous quantitative determination of naproxen, its metabolite 6-Odesmethylnaproxen and their five conjugates in plasma and urine samples by highperformance liquid chromatography on dynamically modified silica, J. Chromatogr., 10 (1992) 325-33.
  • 4. J.O. Miners, S. Coulter, R.H. Tukey, M.E. Veronese, D.J. Birkett, Cytochromes P450, 1A2, and 2C9 are responsible for the human hepatic O-demethylation of R-and S-naproxen, Biomed. PharmacothEr., 51 (1996) 1003-1008.
  • 5. D.F. Zhong, L. Sun, L. Liu, H.H. Huang, Microbial transformation of naproxen by Cunninghamella species, Acta Pharmacol. Sin., 24 (2003) 442-447.
  • 6. N.M. Davies, K.E. Anderson, Clinical pharmacokinetics of naproxen, Clin. Pharmacokinet., 32 (1997) 268-293.
  • 7. T. Tracy, C. Marra, S. Wrighton, F. Gonzalez, K. Korzekwa, Involvement of multiple cytochrome P450 isoforms in naproxen O-demethylation, Eur. J. Clin. Pharmacol., 52 (1997) 293-298.
  • 8. K. Fent, A. A. Weston, D. Caminada, Erratum to “Ecotoxicology of human pharmaceuticals”[Aquatic Toxicology 76 (2006) 122–159], Aquat. Toxicol., 78 (2006a) 207.
  • 9. D. Domaradzka, U. Guzik, D. Wojcieszyńska, Biodegradation and biotransformation of polycyclic non-steroidal anti-inflammatory drugs, Rev. Environ. Sci. Biotechnol., 14 (2015) 229-239.
  • 10. H. Hühnerfuss, S. Selke, M. Scheurell, M.R. Shah, S. Nadeem, The drug naproxen and its transformation products as an example for emerging environmental pollutants, Organohalog. Compd., 72 (2010) 467-470.
  • 11. L.D. Buckberry, Cytotoxicity Testing Using Cell Lines, Animal Cell Biotechnology, Humana Press, Totowa, NJ, 1999.
  • 12. M. Isidori, M. Lavorgna, A. Nardelli, A. Parrella, L. Previtera, M. Rubino, Ecotoxicity of naproxen and its phototransformation products, Sci. Total. Environ., 348 (2005) 93-101.
  • 13. F.A. Alherz, D.A. Almarghalani, N.A. Hussein, K. Kurogi, M.C. Liu, A reappraisal of the 6-O-desmethylnaproxen-sulfating activity of the human cytosolic sulfotransferases, Can. J. Physiol. Pharmacol., 95 (2017) 647-651.
  • 14. XXXXXXXXXXXXXXX
  • 15. I. Correia, R. Arantes-Rodrigues, R. Pinto-Leite, I. Gaivão, Effects of naproxen on cell proliferation and genotoxicity in MG-63 osteosarcoma cell line, J. Toxicol. Env. Heal. A, 77 (2014) 916-923.
  • 16. B.I. Cohen, M.K. Pagnillo, B.L. Musikant, A.S. Deutsch, An in vitro study of the cytotoxicity of two root canal sealers, J. Endod., 26 (2000) 228-229.
  • 17. M. Akyol, Z. Akın Polat, S. Özçelik, Ö. Kaya, The effects of strontium chloride on viability of mouse connective tissue fibroblast cells, C.M.J., 35 (2013) 33-38.
  • 18. J. Carmichael, W.G. DeGraff, A.F. Gazdar, J.D. Minna, J.B. Mitchell, Evaluation of a tetrazolium-based semiautomated colorimetric assay: assessment of chemosensitivity testing, Cancer Res., 47 (1987) 936-942.
  • 19. S. Mohan, A. Bustamam, S. Ibrahim, A.S. Al-Zubairi, M. Aspollah, R. Abdullah, M.M. Elhassan, In vitro ultramorphological assessment of apoptosis on CEMss induced by linoleic acid-rich fraction from Typhonium flagelliforme tuber, Evid. Based Complement. Alternat. Med., (2011) 2011.
  • 20. A. Wahab, S. Ibrahim, A.B. Abdul, A.S. Alzubairi, M. Mohamed Elhassan, S.Mohan, In vitro ultramorphological assessment of apoptosis induced by zerumbone on (HeLa), BioMed. Res. Int., (2009) 2009.
  • 21. G. Tan, M. Kaya, A. Tevlek, I. Sargin, T. Baran, Antitumor activity of chitosan from mayfly with comparison to commercially available low, medium and high molecular weight chitosans, In Vitro Cell. Dev. Biol. Anim., 54 (2018) 366-374.
  • 22. E. Marco-Urrea, M. Pérez-Trujillo, P. Blánquez, T. Vicent, G.Caminal, Biodegradation of the analgesic naproxen by Trametes versicolor and identification of intermediates using HPLC-DAD-MS and NMR, Bioresour. Technol., 101 (2010) 2159-2166.
  • 23. E. Ricciotti, G.A. FitzGerald, Prostaglandins and inflammation, Arterioscler. Thromb. Vasc. Biol., 31 (2011) 986-1000.
  • 24. C.E. Smith, S. Soti, T.A. Jones, A. Nakagawa, D. Xue, H. Yin, Non-steroidal anti-inflammatory drugs are caspase inhibitors, Cell Chem. Biol., 24 (2017) 281-292. 25. K. Fent, A.A. Weston, D. Caminada, Ecotoxicology of human pharmaceuticals, Aquat. Toxicol., 76 (2006b) 122-159.
  • 26. C. Carlsson, A.K. Johansson, G. Alvan, K. Bergman, T. Kühler, Are pharmaceuticals potent environmental pollutants?: Part I: Environmental risk assessments of selected active pharmaceutical ingredients, Sci. Total Environ., 364 (2006) 67-87.
  • 27. S. Selke, M. Scheurell, M.R. Shah, H. Hühnerfuss, Identification and enantioselective gas chromatographic mass-spectrometric separation of O-desmethylnaproxen, the main metabolite of the drug naproxen, as a new environmental contaminant, J. Chromatogr. A., 1217 (2010) 419-423.
  • 28. G. Lucena,C. Reyes-Botella, O. García-Martínez, J. Ramos-Torrecillas, E.D.L., Bertos, C. Ruiz, Effect of NSAIDs on the aminopeptidase activity of cultured human osteoblasts, Mol. Cell. Endocrinol., 426 (2016) 146-154.
  • 29. E. De Luna-Bertos, J. Ramos-Torrecillas, O. García-Martínez, A. Guildford, M. Santin, C. Ruiz, Therapeutic doses of nonsteroidal anti-inflammatory drugs inhibit osteosarcoma MG-63 osteoblast-like cells maturation, viability, and biomineralization potential, Sci. World J., (2013) 2013.
  • 30. H. Axelsson, C. Lönnroth, M. Andersson, K. Lundholm, Mechanisms behind COX-1 and COX-2 inhibition of tumor growth in vivo, Int. J. Oncol., 37 (2010) 1143.
  • 31. L. Díaz‐Rodríguez, O. García‐Martínez, M. Arroyo‐Morales, C. Reyes‐Botella, C. Ruiz, Antigenic Phenotype and Phagocytic Capacity of MG‐63 Osteosarcoma Line, Ann. N. Y. Acad. Sci., 1173 (2009) E46-E54.
  • 32. L. Díaz-Rodríguez, O. García-Martínez, E. De Luna-Bertos, J. Ramos-Torrecillas, C. Ruiz, Effect of ibuprofen on proliferation, differentiation, antigenic expression, and phagocytic capacity of osteoblasts, J. Bone Miner. Metab., 30 (2012a) 554-560.
  • 33. L. Díaz-Rodríguez, O. García-Martínez, M.A. Morales, L. Rodríguez-Pérez, B. Rubio-Ruiz, C. Ruiz, Effects of indomethacin, nimesulide, and diclofenac on human MG-63 osteosarcoma cell line, Biol. Res. Nurs., 14 (2012b) 98-107.
  • 34. E. De Luna-Bertos, J. Ramos-Torrecillas, O. García-Martínez, L. Diaz-Rodriguez, C. Ruiz, Effect of aspirin on cell growth of human MG-63 osteosarcoma line, Sci. World J., (2012) 2012.
  • 35. A. Aresta, T. Carbonara, F. Palmisano, C.G. Zambonin, Profiling urinary metabolites of naproxen by liquid chromatography–electrospray mass spectrometry, J. Pharm. Biomed. Anal., 41 (2006) 1312-1316.
There are 34 citations in total.

Details

Primary Language English
Subjects Engineering
Journal Section Articles
Authors

Esin Akbay 0000-0002-0797-8322

Y. Doruk Aracagök This is me

Ali Hakan Göker 0000-0002-9366-6949

Mehmet Ali Onur 0000-0002-3630-7982

Nilüfer Cihangir 0000-0002-0830-635X

Project Number Yok
Publication Date January 1, 2021
Acceptance Date October 8, 2020
Published in Issue Year 2021

Cite

APA Akbay, E., Aracagök, Y. D., Göker, A. H., Onur, M. A., et al. (2021). In Vitro Evaluation Of Naproxen Metabolite, O-Desmethylnaproxen On A Mouse Connective Tissue Fibroblast Cells. Hacettepe Journal of Biology and Chemistry, 49(1), 25-36. https://doi.org/10.15671/hjbc.680564
AMA Akbay E, Aracagök YD, Göker AH, Onur MA, Cihangir N. In Vitro Evaluation Of Naproxen Metabolite, O-Desmethylnaproxen On A Mouse Connective Tissue Fibroblast Cells. HJBC. January 2021;49(1):25-36. doi:10.15671/hjbc.680564
Chicago Akbay, Esin, Y. Doruk Aracagök, Ali Hakan Göker, Mehmet Ali Onur, and Nilüfer Cihangir. “In Vitro Evaluation Of Naproxen Metabolite, O-Desmethylnaproxen On A Mouse Connective Tissue Fibroblast Cells”. Hacettepe Journal of Biology and Chemistry 49, no. 1 (January 2021): 25-36. https://doi.org/10.15671/hjbc.680564.
EndNote Akbay E, Aracagök YD, Göker AH, Onur MA, Cihangir N (January 1, 2021) In Vitro Evaluation Of Naproxen Metabolite, O-Desmethylnaproxen On A Mouse Connective Tissue Fibroblast Cells. Hacettepe Journal of Biology and Chemistry 49 1 25–36.
IEEE E. Akbay, Y. D. Aracagök, A. H. Göker, M. A. Onur, and N. Cihangir, “In Vitro Evaluation Of Naproxen Metabolite, O-Desmethylnaproxen On A Mouse Connective Tissue Fibroblast Cells”, HJBC, vol. 49, no. 1, pp. 25–36, 2021, doi: 10.15671/hjbc.680564.
ISNAD Akbay, Esin et al. “In Vitro Evaluation Of Naproxen Metabolite, O-Desmethylnaproxen On A Mouse Connective Tissue Fibroblast Cells”. Hacettepe Journal of Biology and Chemistry 49/1 (January 2021), 25-36. https://doi.org/10.15671/hjbc.680564.
JAMA Akbay E, Aracagök YD, Göker AH, Onur MA, Cihangir N. In Vitro Evaluation Of Naproxen Metabolite, O-Desmethylnaproxen On A Mouse Connective Tissue Fibroblast Cells. HJBC. 2021;49:25–36.
MLA Akbay, Esin et al. “In Vitro Evaluation Of Naproxen Metabolite, O-Desmethylnaproxen On A Mouse Connective Tissue Fibroblast Cells”. Hacettepe Journal of Biology and Chemistry, vol. 49, no. 1, 2021, pp. 25-36, doi:10.15671/hjbc.680564.
Vancouver Akbay E, Aracagök YD, Göker AH, Onur MA, Cihangir N. In Vitro Evaluation Of Naproxen Metabolite, O-Desmethylnaproxen On A Mouse Connective Tissue Fibroblast Cells. HJBC. 2021;49(1):25-36.

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