Oxidative Stress in Gastric Ulcers: Mechanisms, Pathogenesis, and Therapeutic Insights

Urwela Sahare; Jugalkishore Vyas; Vivek Paithankar; Anjali Wankhade

doi:10.52711/2321-5836.2026.00031

Research Journal of Pharmacology and Pharmacodynamics

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2321-5836 (Online)
0975-4407 (Print)

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Oxidative Stress in Gastric Ulcers: Mechanisms, Pathogenesis, and Therapeutic Insights

Author(s): Urwela Sahare, Jugalkishore Vyas, Vivek Paithankar, Anjali Wankhade

Email(s): urwela160802@gmail.com

DOI: 10.52711/2321-5836.2026.00031

Address: Urwela Sahare*, Jugalkishore Vyas, Vivek Paithankar, Anjali Wankhade
Department of Pharmacology, Vidyabharti College of Pharmacy, Amravati, Maharashtra, India - 444602.
*Corresponding Author

Published In: Volume - 18, Issue - 3, Year - 2026

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ABSTRACT:
Gastric ulcer disease continues to be a significant global public health issue, resulting from the disruption of the stomach mucosal barrier, an increase in aggressive factors, or a decrease in defensive factors. Oxidative stress has been recognized as a key pathogenic factor that drives ulcer development and disease progression among several pathogenic contributors. Reactive oxygen species generated from mitochondrial activity, inflammatory responses, and environmental exposures play a major role in the macromolecule destruction, such as lipids, proteins, and nucleic acids. Such damage disrupts mucosal homeostasis, potentiates inflammatory signaling, and delays resolution of tissue repair. Several endogenous antioxidant defence mechanisms, including enzymatic and non-enzymatic components, are present in the cells and work to reduce this imbalance. However, they are unable to perform when the synthesis of reactive intermediates is excessive. Several biomarkers, malondialdehyde, nitric oxide, and myeloperoxidase, provide information about the level of oxidative damage and disease progression. Therapeutics targeting oxidative pathways, including conventional drugs, natural compounds, and novel nanocarrier systems, showed a promising impact on mucosal protective and healing mechanisms. Here, we emphasize the mechanistic role of oxidative imbalance in gastric ulceration; the role of oxidative imbalance in various etiological conditions; and both current and emerging treatments that target the restoration of cellular homeostasis and the resulting disease outcome.

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Cite this article:
Urwela Sahare, Jugalkishore Vyas, Vivek Paithankar, Anjali Wankhade. Oxidative Stress in Gastric Ulcers: Mechanisms, Pathogenesis, and Therapeutic Insights. Research Journal of Pharmacology and Pharmacodynamics.2026;18(3):229-7. doi: 10.52711/2321-5836.2026.00031

Cite(Electronic):
Urwela Sahare, Jugalkishore Vyas, Vivek Paithankar, Anjali Wankhade. Oxidative Stress in Gastric Ulcers: Mechanisms, Pathogenesis, and Therapeutic Insights. Research Journal of Pharmacology and Pharmacodynamics.2026;18(3):229-7. doi: 10.52711/2321-5836.2026.00031 Available on: https://www.rjppd.org/AbstractView.aspx?PID=2026-18-3-2

13. REFERENCES:
1. Malik TF, Gnanapandithan K, Singh K. Peptic ulcer disease. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2026 Jan–. Updated 2023 Jun 5.
2. Zullo A, Hassan C, Campo SMA, Morini S. Bleeding peptic ulcer in the elderly: risk factors and prevention strategies. Drugs Aging. 2007; 24(10): 815–828.
3. Huang CY, Lai WY, Sun MF, et al. Prescription patterns of traditional Chinese medicine for peptic ulcer disease in Taiwan: a nationwide population-based study. J Ethnopharmacol. 2015; 176: 311–320.
4. Menon G, El-Nakeep S, Babiker HM. Gastric cancer. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2026 Jan–. Updated 2024 Oct 28.
5. Dash UC, Bhol NK, Swain SK, Samal RR, Nayak PK, Raina V, et al. Oxidative stress and inflammation in the pathogenesis of neurological disorders: mechanisms and implications. Acta Pharm Sin B. 2025; 15(1): 15–34. doi:10.1016/j.apsb.2024.10.004.
6. Pizzino G, Irrera N, Cucinotta M, Pallio G, Mannino F, Arcoraci V, et al. Oxidative stress: harms and benefits for human health. Oxid Med Cell Longev. 2017; 2017: 8416763. doi:10.1155/2017/8416763.
7. Sabir S, Jan A. Physiology, immune response. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2026 Jan–. Updated 2025 Dec 1.
8. Vadivelan R, Dhanabal SP, Raja Rajeswari, Shanish A, Elango K, Suresh B. Oxidative stress in diabetes—A key therapeutic agent. Res J Pharmacol Pharmacodyn. 2010; 2(3): 221–227.
9. Pathade PA, Ahire YS, Bairagi VA, Abhang DR. Antioxidant therapy in cognitive dysfunction associated with diabetes mellitus: an overview. Res J Pharmacol Pharmacodyn. 2011; 3(2): 39–44.
10. Zong Y, Li H, Liao P, Chen L, Pan Y, Zheng Y, et al. Mitochondrial dysfunction: mechanisms and advances in therapy. Signal Transduct Target Ther. 2024; 9(1): 124. doi:10.1038/s41392-024-01839-8.
11. Chen L, Deng H, Cui H, Fang J, Zuo Z, Deng J, et al. Inflammatory responses and inflammation-associated diseases in organs. Oncotarget. 2017; 9(6): 7204–7218. doi:10.18632/oncotarget. 23208.
12. Mahurkar N, Hasan SMU, Malpani A, Manjunath C. Evaluation of gastroprotective influence of vitamin C, melatonin, rabeprazole, and their combination in ethanol-induced ulcer model. Res J Pharmacol Pharmacodyn. 2013; 5(3): 155–161.
13. Cherrada N, Chemsa AE, Gheraissa N, Laib I, Gueboudji Z, El-Shazly M, et al. Gastroprotective efficacy of North African medicinal plants: a review on their therapeutic potential for peptic ulcers. Food Sci Nutr. 2024; 12(11): 8793–8824. doi:10.1002/fsn3.4536.
14. Wang F, Liu J, Hu X, Zhong Y, Wen F, Tang X, et al. The influence on oxidative stress markers, inflammatory factors, and intestinal injury-related molecules in the Wahui pigeon induced by lipopolysaccharide. PLoS One. 2021; 16(5): e0251462. doi:10.1371/journal.pone.0251462.
15. Bilski J, Konturek PC, Konturek SJ, Cieszkowski M, Czarnobilski K. Role of endogenous nitric oxide in the control of gastric acid secretion, blood flow, and gastrin release in conscious dogs. Regul Pept. 1994; 53(3): 175–184. doi:10.1016/0167-0115(94)90166-X.
16. Tarnawski AS, Jones MK. The role of epidermal growth factor (EGF) and its receptor in mucosal protection, adaptation to injury, and ulcer healing: involvement of EGF-R signal transduction pathways. J Clin Gastroenterol. 1998; 27 Suppl 1: S12–S20. doi:10.1097/00004836-199800001-00004.
17. Kim HS, Hwang KY, Chung IK, et al. Tissue plasminogen activator and plasminogen activator inhibitor type 1 gene polymorphism in patients with gastric ulcer complicated with bleeding. J Korean Med Sci. 2003; 18(1): 58–64. doi:10.3346/jkms.2003.18.1.58.
18. Damayanthi D, Prasad KVSRG. Evaluation of antidiabetic and antioxidant activity of n-cinnamoyl metformin analogues. Res J Pharmacol Pharmacodyn. 2017; 9(2): 81–87.
19. Sies H, Jones DP. Reactive oxygen species (ROS) are pleiotropic physiological signalling agents. Nat Rev Mol Cell Biol. 2020; 21(7): 363–383. doi:10.1038/s41580-020-0230-3.
20. Brunelle JK, Letai A. Control of mitochondrial apoptosis by the Bcl-2 family. J Cell Sci. 2009; 122(Pt 4): 437–441. doi:10.1242/jcs. 031682.
21. Babu VNK, Khurana N. A review on mitochondrial dysfunction and oxidative stress due to complex I in Parkinson's disease. Res J Pharmacol Pharmacodyn. 2021; 13(4): 167–170.
22. Alexander A, Tripathi DK, Ajazuddin, Singh M, Sahu M, Swarna. Multidose therapy (MDT) treatment for Helicobacter pylori infection leading to gastric ulcer and carcinoma: a review. Res J Pharmacol Pharmacodyn. 2011; 3(3): 140–147.
23. Maity P, Bindu S, Choubey V, et al. Lansoprazole protects and heals gastric mucosa from NSAID-induced gastropathy by inhibiting mitochondrial and Fas-mediated death pathways with concurrent induction of mucosal cell renewal. J Biol Chem. 2008; 283: 14391–14401.
24. Gotz JM, Veenendaal RA, Biemond I, Muller ES, Veselic M, Lamers CB. Serum gastrin and mucosal somatostatin in Helicobacter pylori-associated gastritis. Scand J Gastroenterol. 1995; 30(11): 1064–1068.
25. Gangoni A, Suneetha B, Sunanda S, Ravindrababu S. Hypolipidemic and antioxidant activity of methanolic leaf extract of Ochna obtusata on high-fat diet-induced obesity in rats. Res J Pharmacol Pharmacodyn. 2015; 7(1): 1–4.
26. Rizo-Téllez SA, Sekheri M, Filep JG. Myeloperoxidase: regulation of neutrophil function and target for therapy. Antioxidants (Basel). 2022; 11(11): 2302. doi:10.3390/antiox11112302.
27. Zhang W, Zhong R, Qu X, Xiang Y, Ji M. Effect of 8-hydroxyguanine DNA glycosylase 1 on the function of immune cells. Antioxidants (Basel). 2023; 12(6): 1300. doi:10.3390/antiox12061300.
28. Cordiano R, Di Gioacchino M, Mangifesta R, Panzera C, Gangemi S, Minciullo PL. Malondialdehyde as a potential oxidative stress marker for allergy-oriented diseases: an update. Molecules. 2023; 28(16): 5979. doi:10.3390/molecules28165979.
29. Gnatyuk O, Skorokhod O, Damin A, Chaika M, Naeimaeirouhani F, Pica L, et al. Structural impact of 4-hydroxynonenal modification on human cytochrome CYP4F11. Chem Med Chem. 2026; 21(2): e202500935. doi:10.1002/cmdc. 202500935.
30. Cracowski JL, Durand T, Bessard G. Isoprostanes as a biomarker of lipid peroxidation in humans: physiology, pharmacology and clinical implications. Trends Pharmacol Sci. 2002; 23(8): 360–366.
31. Nyström T. Role of oxidative carbonylation in protein quality control and senescence. EMBO J. 2005; 24(7): 1311–1317. doi:10.1038/sj.emboj.7600599.
32. Bandookwala M, Sengupta P. 3-Nitrotyrosine: a versatile oxidative stress biomarker for major neurodegenerative diseases. Int J Neurosci. 2020; 130(10): 1047–1062.
33. Goriuc A, Cojocaru KA, Luchian I, Ursu RG, Butnaru O, Foia L. Using 8-hydroxy-2'-deoxyguanosine (8-OHdG) as a reliable biomarker for assessing periodontal disease associated with diabetes. Int J Mol Sci. 2024; 25(3): 1425. doi:10.3390/ijms25031425.
34. Collins AR. The comet assay for DNA damage and repair: principles, applications, and limitations. Mol Biotechnol. 2004; 26(3): 249–261.
35. Biradar KV, Patil CB, Chivde BV, Malipatil MH, Biradar SD. Effect of superoxide dismutase mimetic tempol on dexamethasone-induced insulin resistance—role of oxidative stress. Res J Pharmacol Pharmacodyn. 2011; 3(3): 134–137.
36. Nandi A, Yan LJ, Jana CK, Das N. Role of catalase in oxidative stress- and age-associated degenerative diseases. Oxid Med Cell Longev. 2019; 2019: 9613090. doi:10.1155/2019/9613090.
37. Pei J, Pan X, Wei G, Hua Y. Research progress of glutathione peroxidase family (GPX) in redox. Front Pharmacol. 2023;14:1147414. doi:10.3389/fphar. 2023.1147414.
38. Georgiou-Siafis SK, Tsiftsoglou AS. The key role of GSH in keeping the redox balance in mammalian cells: mechanisms and significance of GSH in detoxification via formation of conjugates. Antioxidants (Basel). 2023; 12(11): 1953. doi:10.3390/antiox12111953.
39. Zitka O, Skalickova S, Gumulec J, Masarik M, Adam V, Hubalek J, et al. Redox status expressed as the GSH: GSSG ratio as a marker for oxidative stress in paediatric tumour patients. Oncol Lett. 2012; 4(6): 1247–1253. doi:10.3892/ol.2012.931.
40. Mijatović S, Savić-Radojević A, Plješa-Ercegovac M, Simić T, Nicoletti F, Maksimović-Ivanić D. The double-faced role of nitric oxide and reactive oxygen species in solid tumors. Antioxidants (Basel). 2020; 9(5): 374. doi:10.3390/antiox9050374.
41. Siraki AG. The many roles of myeloperoxidase: from inflammation and immunity to biomarkers, drug metabolism, and drug discovery. Redox Biol. 2021; 46: 102109. doi:10.1016/j.redox.2021.102109.
42. Jaydeokar AV, Bandawane DD, Nipate SS, Chaudhari PD. Natural antioxidants: a review on therapeutic applications. Res J Pharmacol Pharmacodyn. 2012; 4(1): 55–61.
43. Johnson DB, Gorle A, Paleti SK, Javvadi A. Anti-gastric ulcer studies on certain Siddha drugs. Res J Pharmacol Pharmacodyn. 2011; 3(3): 123–128.
44. Shah N, Gossman W. Omeprazole. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2026 Jan–. Updated 2023 Feb 7.
45. Fornai M, Colucci R, Antonioli L, Ghisu N, Tuccori M, Blandizzi C, et al. Effects of pantoprazole on ulcer healing delay associated with NSAID treatment. Naunyn Schmiedebergs Arch Pharmacol. 2009; 379(3): 305–313. doi:10.1007/s00210-008-0355-y.
46. Laine L. Esomeprazole in the treatment of Helicobacter pylori. Aliment Pharmacol Ther. 2002;16 Suppl 4: 115–118. doi:10.1046/j.1365-2036.16.s4.13.x.
47. Langtry HD, Markham A. Rabeprazole: a review of its use in acid-related gastrointestinal disorders. Drugs. 1999; 58(4): 725–742. doi:10.2165/00003495-199958040-00014.
48. Croom KF, Scott LJ. Lansoprazole in the treatment of gastro-oesophageal reflux disease in children and adolescents. Drugs. 2005; 65(15): 2129–2137. doi:10.2165/00003495-200565150-00005.
49. Patel P, Ahlawat R. Famotidine. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2026 Jan–. Updated 2025 Sep 14.
50. Nugent CC, Falkson SR, Terrell JM. H2 blockers. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2026 Jan–. Updated 2024 Aug 11.
51. Pino MA, Azer SA. Cimetidine. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2026 Jan–. Updated 2023 Mar 6.
52. Kudaravalli P, Patel P, John S. Sucralfate. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2026 Jan–. Updated 2024 Feb 28.
53. Krugh M, Patel P, Maani CV. Misoprostol. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2026 Jan–. Updated 2024 Dec 11.
54. Graham DY, Lee SY. How to effectively use bismuth quadruple therapy: the good, the bad, and the ugly. Gastroenterol Clin North Am. 2015; 44(3): 537–563. doi:10.1016/j.gtc.2015.05.003.
55. Shih C, Wu I, Wu D, Lei W, Tsay F, Tsai T. Evolution of amoxicillin-based mono-antibiotic regimens for Helicobacter pylori eradication: from ineffectiveness to innovation—a systematic review. 2026:1–17.
56. Vieira RR, Fontes LES, Pacheco RL, Fernandes MAP, Malta PP, Riera R. Proton pump inhibitor- and clarithromycin-based triple therapies for Helicobacter pylori eradication. Cochrane Database Syst Rev. 2020; 9: CD013734. doi:10.1002/14651858.CD013734.
57. Sisson G, Jeong JY, Goodwin A, Bryden L, Rossler N, Lim-Morrison S, et al. Metronidazole activation is mutagenic and causes DNA fragmentation in Helicobacter pylori and in Escherichia coli containing a cloned H. pylori RdxA(+) gene. J Bacteriol. 2000; 182(18): 5091–5096. doi:10.1128/JB.182.18.5091-5096.2000.
58. Sun YC, Zhu MJ, Chen XQ, Yue L, Zhao YR, Wang XJ, et al. Efficacy and safety of modified tetracycline dosing in a quadruple therapy for Helicobacter pylori: a retrospective single-center study. World J Gastroenterol. 2023; 29(22): 3508–3518. doi:10.3748/wjg.v29.i22.3508.
59. Petrovic S, Bita B, Barbinta-Patrascu ME. Nanoformulations in pharmaceutical and biomedical applications: green perspectives. Int J Mol Sci. 2024; 25(11): 5842. doi:10.3390/ijms25115842.
60. Sivadasan D, Sultan MH, Alqahtani SS, Javed S. Cubosomes in drug delivery: a comprehensive review on their structural components, preparation techniques, and therapeutic applications. Biomedicines. 2023; 11(4): 1114. doi:10.3390/biomedicines11041114.
61. Dai X, Shen L. Advances and trends in omics technology development. Front Med (Lausanne). 2022; 9: 911861. doi:10.3389/fmed. 2022.911861.
62. Moratilla-Rivera I, Sánchez M, Valdés-González JA, Gómez-Serranillos MP. Natural products as modulators of the Nrf2 signaling pathway in neuroprotection. Int J Mol Sci. 2023; 24(4): 3748. doi:10.3390/ijms24043748.