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Floretin ve floridzin'in farelerde indometazine bağlı gelişen mide ülserine karşı koruyucu etkileri: potansiyel moleküler mekanizmaların karakterizasyonu

Year 2020, Volume 45, Issue 4, 1459 - 1466, 27.12.2020
https://doi.org/10.17826/cumj.734911

Abstract

Amaç: Bu çalışmada farelerde indometazine bağlı ülser modelinde, floretin ve floridzinin potansiyel koruyucu etkilerini incelemeyi amaçlanmıştır. Gereç ve Yöntem: Toplam 54 dişi Balb/C faresi dokuz gruba ayrıldı. Famotidin standart anti-ülser madde olarak kullanıldı. Floretin ve floridzin, tedavi gruplarına 50 ve 100 mg/kg dozlarında verildi. Deneysel prosedürlerden sonra, mide dokusunda oksidatif parametreleri (SOD, GSH ve MDA), enflamatuar sitokin TNF-α ve COX1 ve COX2 mRNA ekspresyonları analiz edildi. Ayrıca, floretin ve floridzinin anti-ülser etki mekanizmasını açıklığa kavuşturmak için ülserli alanların sayısal yoğunlukları analiz edilmiştir. Bulgular: Floretin ve floridzin, indometazine bağlı gelişen ülser oluşumunu doza bağımlı olarak azalttı. İndometazin uygulamasından sonra enflamasyon ve oksidatif stresin arttığı belirlendi. Floretin ve floridzin tedavisi indometazin ile tedavi edilen gruba kıyasla tüm parametreleri normalleştirmiştir. Tedavilerin ardından, indomethazin grubuna kıyasla, SOD aktiviteleri ve GSH düzeyleri yükselirken, MDA düzeyleri azalmıştır. Floretin ve floridzin uygulamarının TNF-α, COX1 ve COX2 mRNA ekspresyonlarını azalttığı tespit edildi. Sonuç: Sonuçlarımız oksidatif stres ve enflamasyona karşı potansiyel düzenleyici etkileri nedeniyle floretin ve floridzinin peptik ülser hastalığı için alternatif bir tedavi olabileceğini göstermiştir.

References

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Risk of upper gastrointestinal ulcer bleeding associated with selective cyclo-oxygenase-2 inhibitors, traditional non-aspirin non-steroidal anti-inflammatory drugs, aspirin and combinations. Gut. 2006;55:1731-8. Referans7. Silverstein FE, Graham DY, Senior JR, Davies HW, Struthers BJ, Bittman RM, et al. Misoprostol reduces serious gastrointestinal complications in patients with rheumatoid arthritis receiving nonsteroidal anti-inflammatory drugs. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 1995;123:241-9. Referans8. Poorvashree J and Suneela D. Novel drug delivery of dual acting prodrugs of hydroxychloroquine with aryl acetic acid NSAIDs: Design, kinetics and pharmacological study. Drug Deliv Transl Res. 2017;7:709-30. Referans9. Musumba C, Pritchard DM and Pirmohamed M. Review article: cellular and molecular mechanisms of NSAID-induced peptic ulcers. Aliment Pharmacol Ther. 2009;30:517-31. Referans10. Halabi MF, Shakir RM, Bardi DA, Al-Wajeeh NS, Ablat A, Hassandarvish P, et al. Gastroprotective activity of ethyl-4-[(3,5-di-tert-butyl-2-hydroxybenzylidene) amino]benzoate against ethanol-induced gastric mucosal ulcer in rats. PLoS One. 2014;9:e95908. Referans11. Handa O, Naito Y, Fukui A, Omatsu T and Yoshikawa T. The impact of non-steroidal anti-inflammatory drugs on the small intestinal epithelium. J Clin Biochem Nutr. 2014;54:2-6. Referans12. Chao EC and Henry RR. SGLT2 inhibition--a novel strategy for diabetes treatment. Nat Rev Drug Discov. 2010;9:551-9. Referans13. Gosch C, Halbwirth H and Stich K. Phloridzin: biosynthesis, distribution and physiological relevance in plants. Phytochemistry. 2010;71:838-43. Referans14. Li X, Chen B, Xie H, He Y, Zhong D and Chen D. Antioxidant Structure(-)Activity Relationship Analysis of Five Dihydrochalcones. Molecules. 2018;23: Referans15. Huang WC, Fang LW and Liou CJ. Phloretin Attenuates Allergic Airway Inflammation and Oxidative Stress in Asthmatic Mice. Front Immunol. 2017;8:134. Referans16. Zuo AR, Yu YY, Shu QL, Zheng LX, Wang XM, Peng SH, et al. Hepatoprotective effects and antioxidant, antityrosinase activities of phloretin and phloretin isonicotinyl hydrazone. J Chin Med Assoc. 2014;77:290-301. Referans17. Barreca D, Curro M, Bellocco E, Ficarra S, Lagana G, Tellone E, et al. Neuroprotective effects of phloretin and its glycosylated derivative on rotenone-induced toxicity in human SH-SY5Y neuronal-like cells. Biofactors. 2017;43:549-57. Referans18. Nakamura Y, Watanabe S, Miyake N, Kohno H and Osawa T. Dihydrochalcones: evaluation as novel radical scavenging antioxidants. J Agric Food Chem. 2003;51:3309-12. Referans19. Albayrak A, Halici Z, Cadirci E, Polat B, Karakus E, Bayir Y, et al. Inflammation and peripheral 5-HT7 receptors: the role of 5-HT7 receptors in carrageenan induced inflammation in rats. Eur J Pharmacol. 2013;715:270-9. 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Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25:402-8. Referans26. Lakshmi V, Singh N, Shrivastva S, Mishra SK, Dharmani P, Mishra V, et al. Gedunin and photogedunin of Xylocarpus granatum show significant anti-secretory effects and protect the gastric mucosa of peptic ulcer in rats. Phytomedicine. 2010;17:569-74. Referans27. Barboza KRM, Coco LZ, Alves GM, Peters B, Vasquez EC, Pereira TMC, et al. Gastroprotective effect of oral kefir on indomethacin-induced acute gastric lesions in mice: Impact on oxidative stress. Life Sci. 2018;209:370-76. Referans28. Oral A, Halici Z, Bayir Y, Topcu A, Un H, Bilgin AO, et al. Effects of oral zinc administration on long-term ipsilateral and contralateral testes damage after experimental testis ischaemia-reperfusion. Andrologia. 2017;49: Referans29. Kunak CS, Ugan RA, Cadirci E, Karakus E, Polat B, Un H, et al. Nephroprotective potential of carnitine against glycerol and contrast-induced kidney injury in rats through modulation of oxidative stress, proinflammatory cytokines, and apoptosis. Br J Radiol. 2016;89:20140724. Referans30. Mahmoud YI and Abd El-Ghffar EA. Spirulina ameliorates aspirin-induced gastric ulcer in albino mice by alleviating oxidative stress and inflammation. Biomed Pharmacother. 2019;109:314-21. Referans31. Naito Y and Yoshikawa T. Oxidative stress involvement and gene expression in indomethacin-induced gastropathy. Redox Rep. 2006;11:243-53. Referans32. Halici Z, Polat B, Cadirci E, Topcu A, Karakus E, Kose D, et al. Inhibiting renin angiotensin system in rate limiting step by aliskiren as a new approach for preventing indomethacin induced gastric ulcers. Chem Biol Interact. 2016;258:266-75. Referans33. Suleyman H, Albayrak A, Bilici M, Cadirci E and Halici Z. Different mechanisms in formation and prevention of indomethacin-induced gastric ulcers. Inflammation. 2010;33:224-34. Referans34. Odabasoglu F, Cakir A, Suleyman H, Aslan A, Bayir Y, Halici M, et al. Gastroprotective and antioxidant effects of usnic acid on indomethacin-induced gastric ulcer in rats. J Ethnopharmacol. 2006;103:59-65. Referans35. Halici M, Odabasoglu F, Suleyman H, Cakir A, Aslan A and Bayir Y. Effects of water extract of Usnea longissima on antioxidant enzyme activity and mucosal damage caused by indomethacin in rats. Phytomedicine. 2005;12:656-62. Referans36. Wang SP, Lin SC, Li S, Chao YH, Hwang GY and Lin CC. Potent Antiarthritic Properties of Phloretin in Murine Collagen-Induced Arthritis. Evid Based Complement Alternat Med. 2016;2016:9831263. Referans37. Deng G, Wang J, Zhang Q, He H, Wu F, Feng T, et al. Hepatoprotective effects of phloridzin on hepatic fibrosis induced by carbon tetrachloride against oxidative stress-triggered damage and fibrosis in rats. Biol Pharm Bull. 2012;35:1118-25. Referans38. Schoenberg MH, Buchler M, Pietrzyk C, Uhl W, Birk D, Eisele S, et al. Lipid peroxidation and glutathione metabolism in chronic pancreatitis. Pancreas. 1995;10:36-43. Referans39. Kwiecien S, Jasnos K, Magierowski M, Sliwowski Z, Pajdo R, Brzozowski B, et al. Lipid peroxidation, reactive oxygen species and antioxidative factors in the pathogenesis of gastric mucosal lesions and mechanism of protection against oxidative stress - induced gastric injury. J Physiol Pharmacol. 2014;65:613-22. Referans40. Dengiz GO, Odabasoglu F, Halici Z, Cadirci E and Suleyman H. Gastroprotective and antioxidant effects of montelukast on indomethacin-induced gastric ulcer in rats. J Pharmacol Sci. 2007;105:94-102. Referans41. Cadirci E, Suleyman H, Aksoy H, Halici Z, Ozgen U, Koc A, et al. Effects of Onosma armeniacum root extract on ethanol-induced oxidative stress in stomach tissue of rats. Chem Biol Interact. 2007;170:40-8. Referans42. Liu Y, Zhang L and Liang J. Activation of the Nrf2 defense pathway contributes to neuroprotective effects of phloretin on oxidative stress injury after cerebral ischemia/reperfusion in rats. J Neurol Sci. 2015;351:88-92. Referans43. Saritemur M, Un H, Cadirci E, Karakus E, Akpinar E, Halici Z, et al. Tnf-alpha inhibition by infliximab as a new target for the prevention of glycerol-contrast-induced nephropathy. Environ Toxicol Pharmacol. 2015;39:577-88. Referans44. Antonisamy P, Arasu MV, Dhanasekaran M, Choi KC, Aravinthan A, Kim NS, et al. Protective effects of trigonelline against indomethacin-induced gastric ulcer in rats and potential underlying mechanisms. Food Funct. 2016;7:398-408. Referans45. Pinho-Ribeiro FA, Hohmann MS, Borghi SM, Zarpelon AC, Guazelli CF, Manchope MF, et al. Protective effects of the flavonoid hesperidin methyl chalcone in inflammation and pain in mice: role of TRPV1, oxidative stress, cytokines and NF-kappaB. Chem Biol Interact. 2015;228:88-99. Referans46. Ciftci O and Ozdemir I. Protective effects of quercetin and chrysin against 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induced oxidative stress, body wasting and altered cytokine productions in rats. Immunopharmacol Immunotoxicol. 2011;33:504-8. Referans47. Heeba GH, Hassan MK and Amin RS. Gastroprotective effect of simvastatin against indomethacin-induced gastric ulcer in rats: role of nitric oxide and prostaglandins. Eur J Pharmacol. 2009;607:188-93. Referans48. Zheng W, Chen C, Zhang C, Cai L and Chen H. The protective effect of phloretin in osteoarthritis: an in vitro and in vivo study. Food Funct. 2018;9:263-78. Referans49. Khalifa MMA, Bakr AG and Osman AT. Protective effects of phloridzin against methotrexate-induced liver toxicity in rats. Biomed Pharmacother. 2017;95:529-35.

Protective effects of phloretin and phloridzin on indomethacin-induced gastric ulcers in mice: characterization of potential molecular mechanisms

Year 2020, Volume 45, Issue 4, 1459 - 1466, 27.12.2020
https://doi.org/10.17826/cumj.734911

Abstract

Purpose: We aimed to examine the potential protective effects of phloretin and phloridzin in indomethacin induced ulcer model in mice. Materials and Methods: In total 54 female Balb/C mice were separated into nine groups. Famotidine was used as standard antiulcer agent. The phloretin and phloridzin was given at the doses of 50 and 100 mg/kg as a pre-treatment. After experimental procedures stomach tissue oxidative parameters (SOD, GSH and MDA), inflammatory cytokine TNF-α, and COX1 and COX2 mRNA expressions were analyzed. In addition, to clarify antiulcer effect mechanism of phloretin and phloridzin, numerical densities of ulcerative areas were analyzed. Results: Phloretin and phloridzin inhibited indomethacin-induced ulcer formation in dose dependent manner. Tissue inflammation and oxidative stress were increased after the indomethacin administration. Phloretin and phloridzin treatment normalized all parameters compared to indomethacin treated group. After the treatments, SOD activities and GSH levels were increased while MDA levels were decreased. Phloretin and phloridzin treatments decreased TNF-α, COX1 and COX2 mRNA expressions. Conclusion: Our results showed that phloretin and phloridzin may be an alternative treatment for peptic ulcer disease due to their potential regulatory effects against oxidative stress and inflammation.

References

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Risk of upper gastrointestinal ulcer bleeding associated with selective cyclo-oxygenase-2 inhibitors, traditional non-aspirin non-steroidal anti-inflammatory drugs, aspirin and combinations. Gut. 2006;55:1731-8. Referans7. Silverstein FE, Graham DY, Senior JR, Davies HW, Struthers BJ, Bittman RM, et al. Misoprostol reduces serious gastrointestinal complications in patients with rheumatoid arthritis receiving nonsteroidal anti-inflammatory drugs. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 1995;123:241-9. Referans8. Poorvashree J and Suneela D. Novel drug delivery of dual acting prodrugs of hydroxychloroquine with aryl acetic acid NSAIDs: Design, kinetics and pharmacological study. Drug Deliv Transl Res. 2017;7:709-30. Referans9. Musumba C, Pritchard DM and Pirmohamed M. Review article: cellular and molecular mechanisms of NSAID-induced peptic ulcers. Aliment Pharmacol Ther. 2009;30:517-31. Referans10. Halabi MF, Shakir RM, Bardi DA, Al-Wajeeh NS, Ablat A, Hassandarvish P, et al. Gastroprotective activity of ethyl-4-[(3,5-di-tert-butyl-2-hydroxybenzylidene) amino]benzoate against ethanol-induced gastric mucosal ulcer in rats. PLoS One. 2014;9:e95908. Referans11. Handa O, Naito Y, Fukui A, Omatsu T and Yoshikawa T. The impact of non-steroidal anti-inflammatory drugs on the small intestinal epithelium. J Clin Biochem Nutr. 2014;54:2-6. Referans12. Chao EC and Henry RR. SGLT2 inhibition--a novel strategy for diabetes treatment. Nat Rev Drug Discov. 2010;9:551-9. Referans13. Gosch C, Halbwirth H and Stich K. Phloridzin: biosynthesis, distribution and physiological relevance in plants. Phytochemistry. 2010;71:838-43. Referans14. Li X, Chen B, Xie H, He Y, Zhong D and Chen D. Antioxidant Structure(-)Activity Relationship Analysis of Five Dihydrochalcones. Molecules. 2018;23: Referans15. Huang WC, Fang LW and Liou CJ. Phloretin Attenuates Allergic Airway Inflammation and Oxidative Stress in Asthmatic Mice. Front Immunol. 2017;8:134. Referans16. Zuo AR, Yu YY, Shu QL, Zheng LX, Wang XM, Peng SH, et al. Hepatoprotective effects and antioxidant, antityrosinase activities of phloretin and phloretin isonicotinyl hydrazone. J Chin Med Assoc. 2014;77:290-301. Referans17. Barreca D, Curro M, Bellocco E, Ficarra S, Lagana G, Tellone E, et al. Neuroprotective effects of phloretin and its glycosylated derivative on rotenone-induced toxicity in human SH-SY5Y neuronal-like cells. Biofactors. 2017;43:549-57. Referans18. Nakamura Y, Watanabe S, Miyake N, Kohno H and Osawa T. Dihydrochalcones: evaluation as novel radical scavenging antioxidants. J Agric Food Chem. 2003;51:3309-12. Referans19. Albayrak A, Halici Z, Cadirci E, Polat B, Karakus E, Bayir Y, et al. Inflammation and peripheral 5-HT7 receptors: the role of 5-HT7 receptors in carrageenan induced inflammation in rats. Eur J Pharmacol. 2013;715:270-9. Referans20. Sun Y, Oberley LW and Li Y. A simple method for clinical assay of superoxide dismutase. Clin Chem. 1988;34:497-500. Referans21. Sedlak J and Lindsay RH. Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman's reagent. Anal Biochem. 1968;25:192-205. Referans22. Ohkawa H, Ohishi N and Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979;95:351-8. Referans23. Bayir Y, Karagoz Y, Karakus E, Albayrak A, Sengul O, Can I, et al. Nigella sativa reduces tissue damage in rat ovaries subjected to torsion and detorsion: oxidative stress, proinflammatory response and histopathological evaluation. Gynecol Obstet Invest. 2012;74:41-9. Referans24. Bayir Y, Cadirci E, Polat B, Kilic Baygutalp N, Albayrak A, Karakus E, et al. Aliskiren - a promising strategy for ovarian ischemia/reperfusion injury protection in rats via RAAS. Gynecol Endocrinol. 2016;32:675-83. Referans25. Livak KJ and Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25:402-8. Referans26. Lakshmi V, Singh N, Shrivastva S, Mishra SK, Dharmani P, Mishra V, et al. Gedunin and photogedunin of Xylocarpus granatum show significant anti-secretory effects and protect the gastric mucosa of peptic ulcer in rats. Phytomedicine. 2010;17:569-74. Referans27. Barboza KRM, Coco LZ, Alves GM, Peters B, Vasquez EC, Pereira TMC, et al. Gastroprotective effect of oral kefir on indomethacin-induced acute gastric lesions in mice: Impact on oxidative stress. Life Sci. 2018;209:370-76. Referans28. Oral A, Halici Z, Bayir Y, Topcu A, Un H, Bilgin AO, et al. Effects of oral zinc administration on long-term ipsilateral and contralateral testes damage after experimental testis ischaemia-reperfusion. Andrologia. 2017;49: Referans29. Kunak CS, Ugan RA, Cadirci E, Karakus E, Polat B, Un H, et al. Nephroprotective potential of carnitine against glycerol and contrast-induced kidney injury in rats through modulation of oxidative stress, proinflammatory cytokines, and apoptosis. Br J Radiol. 2016;89:20140724. Referans30. Mahmoud YI and Abd El-Ghffar EA. Spirulina ameliorates aspirin-induced gastric ulcer in albino mice by alleviating oxidative stress and inflammation. Biomed Pharmacother. 2019;109:314-21. Referans31. Naito Y and Yoshikawa T. Oxidative stress involvement and gene expression in indomethacin-induced gastropathy. Redox Rep. 2006;11:243-53. Referans32. Halici Z, Polat B, Cadirci E, Topcu A, Karakus E, Kose D, et al. Inhibiting renin angiotensin system in rate limiting step by aliskiren as a new approach for preventing indomethacin induced gastric ulcers. Chem Biol Interact. 2016;258:266-75. Referans33. Suleyman H, Albayrak A, Bilici M, Cadirci E and Halici Z. Different mechanisms in formation and prevention of indomethacin-induced gastric ulcers. Inflammation. 2010;33:224-34. Referans34. Odabasoglu F, Cakir A, Suleyman H, Aslan A, Bayir Y, Halici M, et al. Gastroprotective and antioxidant effects of usnic acid on indomethacin-induced gastric ulcer in rats. J Ethnopharmacol. 2006;103:59-65. Referans35. Halici M, Odabasoglu F, Suleyman H, Cakir A, Aslan A and Bayir Y. Effects of water extract of Usnea longissima on antioxidant enzyme activity and mucosal damage caused by indomethacin in rats. Phytomedicine. 2005;12:656-62. Referans36. Wang SP, Lin SC, Li S, Chao YH, Hwang GY and Lin CC. Potent Antiarthritic Properties of Phloretin in Murine Collagen-Induced Arthritis. Evid Based Complement Alternat Med. 2016;2016:9831263. Referans37. Deng G, Wang J, Zhang Q, He H, Wu F, Feng T, et al. Hepatoprotective effects of phloridzin on hepatic fibrosis induced by carbon tetrachloride against oxidative stress-triggered damage and fibrosis in rats. Biol Pharm Bull. 2012;35:1118-25. Referans38. Schoenberg MH, Buchler M, Pietrzyk C, Uhl W, Birk D, Eisele S, et al. Lipid peroxidation and glutathione metabolism in chronic pancreatitis. Pancreas. 1995;10:36-43. Referans39. Kwiecien S, Jasnos K, Magierowski M, Sliwowski Z, Pajdo R, Brzozowski B, et al. Lipid peroxidation, reactive oxygen species and antioxidative factors in the pathogenesis of gastric mucosal lesions and mechanism of protection against oxidative stress - induced gastric injury. J Physiol Pharmacol. 2014;65:613-22. Referans40. Dengiz GO, Odabasoglu F, Halici Z, Cadirci E and Suleyman H. Gastroprotective and antioxidant effects of montelukast on indomethacin-induced gastric ulcer in rats. J Pharmacol Sci. 2007;105:94-102. Referans41. Cadirci E, Suleyman H, Aksoy H, Halici Z, Ozgen U, Koc A, et al. Effects of Onosma armeniacum root extract on ethanol-induced oxidative stress in stomach tissue of rats. Chem Biol Interact. 2007;170:40-8. Referans42. Liu Y, Zhang L and Liang J. Activation of the Nrf2 defense pathway contributes to neuroprotective effects of phloretin on oxidative stress injury after cerebral ischemia/reperfusion in rats. J Neurol Sci. 2015;351:88-92. Referans43. Saritemur M, Un H, Cadirci E, Karakus E, Akpinar E, Halici Z, et al. Tnf-alpha inhibition by infliximab as a new target for the prevention of glycerol-contrast-induced nephropathy. Environ Toxicol Pharmacol. 2015;39:577-88. Referans44. Antonisamy P, Arasu MV, Dhanasekaran M, Choi KC, Aravinthan A, Kim NS, et al. Protective effects of trigonelline against indomethacin-induced gastric ulcer in rats and potential underlying mechanisms. Food Funct. 2016;7:398-408. Referans45. Pinho-Ribeiro FA, Hohmann MS, Borghi SM, Zarpelon AC, Guazelli CF, Manchope MF, et al. Protective effects of the flavonoid hesperidin methyl chalcone in inflammation and pain in mice: role of TRPV1, oxidative stress, cytokines and NF-kappaB. Chem Biol Interact. 2015;228:88-99. Referans46. Ciftci O and Ozdemir I. Protective effects of quercetin and chrysin against 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induced oxidative stress, body wasting and altered cytokine productions in rats. Immunopharmacol Immunotoxicol. 2011;33:504-8. Referans47. Heeba GH, Hassan MK and Amin RS. Gastroprotective effect of simvastatin against indomethacin-induced gastric ulcer in rats: role of nitric oxide and prostaglandins. Eur J Pharmacol. 2009;607:188-93. Referans48. Zheng W, Chen C, Zhang C, Cai L and Chen H. The protective effect of phloretin in osteoarthritis: an in vitro and in vivo study. Food Funct. 2018;9:263-78. Referans49. Khalifa MMA, Bakr AG and Osman AT. Protective effects of phloridzin against methotrexate-induced liver toxicity in rats. Biomed Pharmacother. 2017;95:529-35.

Details

Primary Language English
Subjects Biochemistry and Molecular Biology, Medicine, Research and Experimental
Journal Section Research
Authors

Harun ÜN (Primary Author)
AGRI IBRAHIM CECEN UNIVERSITY, FACULTY OF PHARMACY
0000-0003-1772-282X
Türkiye


Rüstem Anıl UGAN
Atatürk University, Faculty of Pharmacy
0000-0002-4837-2343
Türkiye

Publication Date December 27, 2020
Published in Issue Year 2020, Volume 45, Issue 4

Cite

MLA Ün, H. , Ugan, R. A. "Protective effects of phloretin and phloridzin on indomethacin-induced gastric ulcers in mice: characterization of potential molecular mechanisms" . Cukurova Medical Journal 45 (2020 ): 1459-1466 <https://dergipark.org.tr/en/pub/cumj/article/734911>