Proton Pompası İnhibitörü Olan Pantoprazolün L929 Fibroblast Hücrelerinde Yara İyileşmesi Üzerindeki Etkisi

Year 2026, Volume: 15 Issue: 1 , 43 - 49 , 30.03.2026

Ayşegül Öztürk , Büşra Yıldız , Hilmi Ataseven , Zeynep Deniz Şahin İnan

https://doi.org/10.46810/tdfd.1670872

https://izlik.org/JA87UE78SJ

Abstract

Amaç: Bu çalışmanın amacı, pantoprazolün yara iyileşmesi üzerindeki potansiyel etkilerini L929 fibroblast hücre hattı kullanarak araştırmaktır. Özellikle, pantoprazolün hücre canlılığı, oksidatif stres belirteçleri ve in vitro yara iyileşme süreci üzerindeki etkileri değerlendirilmiştir.
Materyal Metot: L929 fibroblast hücreleri, hücre canlılığını değerlendirmek amacıyla 2.5 ila 40 μM konsantrasyonlarında pantoprazol ile 24 saat süreyle muamele edilmiştir. Oksidatif dengeyi değerlendirmek için 2.5 μM pantoprazol uygulanmış; total antioksidan seviye (TAS) ve total oksidan seviye (TOS) ölçülmüştür. Yara iyileşmesini analiz etmek amacıyla, 0,9 × 1,8 mm boyutlarında standart bir yara alanı oluşturulmuş ve pantoprazol ile tedavi edilen hücrelerin yara bölgesine göçü 24., 36. ve 48. saatlerde değerlendirilmiştir.
Bulgular: Pantoprazol, 5 ila 40 μM arasındaki konsantrasyonlarda doza bağlı anlamlı sitotoksik etki göstermiştir (p < 0.05 ila p < 0.001), buna karşılık 2.5 μM konsantrasyonunda hücre canlılığında anlamlı bir artış saptanmıştır (p < 0.01). TAS seviyeleri anlamlı şekilde artarken (p < 0,05), TOS seviyelerinde anlamlı bir değişiklik gözlenmemiştir (p > 0.05). Pantoprazol uygulanan grupta yara alanı 48. saatte anlamlı olarak daha hızlı kapanmıştır (p < 0.05), ancak 24. ve 36. saatlerde istatistiksel fark saptanmamıştır.
Sonuç: Düşük konsantrasyonlarda pantoprazol, fibroblast canlılığını artırmakta, antioksidan düzeyleri yükseltmekte ve yara iyileşmesini hızlandırmaktadır. Bu bulgular, pantoprazolün doku onarımı ve oksidatif stres modülasyonunda potansiyel terapötik yararlar sağlayabileceğini göstermektedir.

Keywords

Pantoprazol , Yara İyileşmesi , Sitotoksisite

Supporting Institution

TUBİTAK

Project Number

1919B012004230

The Effect of Pantoprazole, a Proton Pump Inhibitor, on Wound Healing in L929 Fibroblast Cells

https://izlik.org/JA87UE78SJ

Abstract

Aim: This study aimed to investigate the potential effects of pantoprazole on wound healing using the L929 fibroblast cell line. Specifically, its impact on cell viability, oxidative stress markers, and the in vitro wound healing process was evaluated.
Material and Method: L929 fibroblast cells were treated with pantoprazole at concentrations between 2.5 and 40 μM for 24 hours to assess cell viability. To evaluate oxidative balance, 2.5 μM pantoprazole was applied, and total antioxidant status (TAS) and total oxidant status (TOS) were measured. For wound healing analysis, a scratch assay was performed by creating a standardized wound area (0.9 × 1.8 mm), and cell migration toward the wound was evaluated at 24-, 36-, and 48-hours post-treatment.
Results: Pantoprazole showed a concentration-dependent cytotoxic effect at doses between 5 and 40 μM (p < 0.05 to p < 0.001), while 2.5 μM significantly enhanced cell viability (p < 0.01). TAS levels were significantly increased (p < 0.05), with no significant change in TOS (p > 0.05). Wound closure was significantly improved at 48 hours in the pantoprazole-treated group (p < 0.05), though earlier time points showed no statistical difference.
Conclusion: At low concentrations, pantoprazole enhances fibroblast viability, boosts antioxidant status, and accelerates wound healing, indicating potential therapeutic utility in tissue repair and oxidative stress modulation.

Keywords

Pantoprazole , Wound Healing , Cytotoxicity

Ethical Statement

Çalışmamızda Etik Kurul gerekmemektedir.

Supporting Institution

TUBİTAK

Project Number

1919B012004230

Thanks

This study was conducted within the scope of the TUBITAK 2209-A project (Project no: 1919B012004230). We would like to thank the Research Center of the Faculty of Medicine, Sivas Cumhuriyet University (CÜTFAM) for providing the necessary facilities for this study.

References

• Parham S, McNally M. Wound Irrigation in Initial Management of Open Fractures. New England Journal of Medicine. 2016 May 5;374(18):1788–90.
• Almadani YH, Vorstenbosch J, Davison PG, Murphy AM. Wound Healing: A Comprehensive Review. Semin Plast Surg. 2021 Aug 15;35(03):141–4.
• Gömeç M, İpek G, Öztürk A, Şahin İnan D. Effect of Wheat Germ Oil on Wound Healing: An In Vitro Study in Fibroblast Cells. Turkish Journal of Science and Health. 2022 Sep 17;
• Pastar I, Balukoff NC, Marjanovic J, Chen VY, Stone RC, Tomic-Canic M. Molecular Pathophysiology of Chronic Wounds: Current State and Future Directions. Cold Spring Harb Perspect Biol. 2023 Apr;15(4):a041243.
• Yıldızhan K, Öztürk A. Quipazine treatment exacerbates oxidative stress in glutamate-induced HT-22 neuronal cells. The European Research Journal. 2022 Jul 4;8(4):521–8.
• Aslan R, Alim A. Synergistic antimicrobial and antibiofilm effects of plant-active ingredients and antibiotics on multidrug-resistant Acinetobacter baumannii. J Appl Microbiol. 2025 Sep 1;136(9).
• Fitzmaurice SD, Sivamani RK, Isseroff RR. Antioxidant Therapies for Wound Healing: A Clinical Guide to Currently Commercially Available Products. Skin Pharmacol Physiol. 2011;24(3):113–26.
• Dunnill C, Patton T, Brennan J, Barrett J, Dryden M, Cooke J, et al. Reactive oxygen species (ROS) and wound healing: the functional role of ROS and emerging ROS‐modulating technologies for augmentation of the healing process. Int Wound J. 2017 Feb 21;14(1):89–96.
• Topal Canbaz G, Keskin ZS, Yokuş A, Aslan R. Biofabrication of copper oxide nanoparticles using Solanum tuberosum L. var. Vitelotte: characterization, antioxidant and antimicrobial activity. Chemical Papers. 2023 Aug 22;77(8):4277–84.
• Keleş ÖF, Demir A, Çiçek HA, Yıldızhan K, Çelik İ. The effect Eremurus spectabilis M. Bieb. on diethylnitrosamine-induced neurotoxicity in hippocampus (cornu ammonis) of rat. Neuro-Cell Molecular Research Research Article Neuro-Cell Mol Res. 2024;1(3):53–9.
• Nakagawa S, Arai Y, Kishida T, Hiraoka N, Tsuchida S, Inoue H, et al. Lansoprazole Inhibits Nitric Oxide and Prostaglandin E2 Production in Murine Macrophage RAW 264.7 Cells. Inflammation. 2012 Jun 2;35(3):1062–8.
• Lazarou J, Pomeranz BH, Corey PN. Incidence of Adverse Drug Reactions in Hospitalized Patients. JAMA. 1998 Apr 15;279(15):1200.
• Taskiran AS, Ergul M, Gunes H, Ozturk A, Sahin B, Ozdemir E. The Effects of Proton Pump Inhibitors (Pantoprazole) on Pentylenetetrazole-Induced Epileptic Seizures in Rats and Neurotoxicity in the SH-SY5Y Human Neuroblastoma Cell Line. Cell Mol Neurobiol. 2021 Jan 1;41(1):173–83.
• Altınkaya E. Proton Pompa İnhibitörlerinin Dispeptik Şikâyet Dışında Kullanım Alanları. In: Ataseven H, Ergül M, editors. Her Yönüyle Proton Pompaları ve Proton Pompa İnhibitörleri. Sivas; 2020. p. 135–9.
• Ghebremariam YT, Cooke JP, Gerhart W, Griego C, Brower JB, Doyle-Eisele M, et al. Pleiotropic effect of the proton pump inhibitor esomeprazole leading to suppression of lung inflammation and fibrosis. J Transl Med. 2015 Dec 1;13(1):249.
• Yılmaz K, Kaleci AO. Effect of Bortezomib, Daptomycin and Their Combination on Antiproliferation in U266 Multiple Myeloma Cell Line. Cumhuriyet Science Journal. 2025 Jun 30;46(2):201–5.
• Joha Z, Başgöz N, Özgür A, Taşkıran AŞ. Bromelain Protects Against PTZ-Induced Glial Damage and Inflammation: An In Vitro and In Silico Study. Cell Biochem Biophys. 2025 Feb 25;
• Şahin B, Karabulut S. Cumhuriyet Medical Journal Sugammadex Causes C6 Glial Cell Death and Exacerbates Hydrogen Peroxide-Induced Oxidative Stress. Cumhuriyet Medical Journal. 2022;44(1):22–7.
• Erel O. A novel automated method to measure total antioxidant response against potent free radical reactions. Clin Biochem. 2004 Feb 1;37(2):112–9.
• Öztürk A, Taşkıran AŞ, Gündoğdu E. The role of oxidative stress in the protective effect of boric acid against glutamate excitotoxicity in C6 glioma cells. Journal of Boron. 2025 Mar;10(1):1–9.
• Peña OA, Martin P. Cellular and molecular mechanisms of skin wound healing. Nat Rev Mol Cell Biol. 2024 Aug 25;25(8):599–616.
• Ihraiz WG, Ahram M, Bardaweel SK. Proton pump inhibitors enhance chemosensitivity, promote apoptosis, and suppress migration of breast cancer cells. Acta Pharmaceutica. 2020 Jun 1;70(2):179–90.
• Lu ZN, Tian B, Guo XL. Repositioning of proton pump inhibitors in cancer therapy. Cancer Chemother Pharmacol. 2017 Nov 31;80(5):925–37.
• Fowler JF, Eubank TA, Garey KW. Proton pump inhibitor effect on macrophage and neutrophil function: a systematic review. Front Immunol. 2024 Dec 24;15.
• Akimoto M, Hashimoto H, Shigemoto M, Maeda A, Yamashita K. Effects of antisecretory agents on angiogenesis during healing of gastric ulcers. J Gastroenterol. 2005 Aug 2;40(7):685–9.
• Masaoka T, Suzuki H, Ishii H. Effect of proton pump inhibitors (PPIs) on wound healing of gastric mucosal cell injury. Japanese journal of clinical medicine. 2004 Mar;62(3):556–60.
• Prause M, Seeliger C, Unger M, van Griensven M, Haug AT. Pantoprazole increases cell viability and function of primary human osteoblasts in vitro. Injury. 2014 Aug;45(8):1156–64.
• Geeviman K, Babu D, Prakash Babu P. Pantoprazole Induces Mitochondrial Apoptosis and Attenuates NF-κB Signaling in Glioma Cells. Cell Mol Neurobiol. 2018 Nov 9;38(8):1491–504.
• Zeng X, Liu L, Zheng M, Sun H, Xiao J, Lu T, et al. Pantoprazole, an FDA-approved proton-pump inhibitor, suppresses colorectal cancer growth by targeting T-cell-originated protein kinase. Oncotarget. 2016 Apr 19;7(16):22460–73.
• Aksoy H. Yara İyileşmesi ve Oksidatif Stress. MARMARA PHARMACEUTCAL JOURNAL. 2014 Sep 8;3(18):153–153.
• Kurahashi T, Fujii J. Roles of Antioxidative Enzymes in Wound Healing. J Dev Biol. 2015 Apr 27;3(2):57–70.
• Numico G, Fusco V, Franco P, Roila F. Proton Pump Inhibitors in cancer patients: How useful they are? A review of the most common indications for their use. Crit Rev Oncol Hematol. 2017 Mar;111:144–51.
• Sahin B, Gunes H. Effect of Pantoprazole, a Proton Pump Inhibitor, on Morphine Tolerance in Rats. Neurochemical Journal. 2024 Dec 18;18(4):789–99.