A novel antioxidant and antiapoptotic role of omeprazole to block gastric ulcer through scavenging of hydroxyl radical

Kaushik Biswas, Uday Bandyopadhyay, Ishita Chattopadhyay, Archana Varadaraj, Esahak Ali, Ranajit K. Banerjee

Research output: Contribution to journalArticle

Abstract

The mechanism of the antiulcer effect of omeprazole was studied placing emphasis on its role to block oxidative damage and apoptosis during ulceration. Dose-response studies on gastroprotection in stress and indomethacin-induced ulcer and inhibition of pylorus ligation-induced acid secretion indicate that omeprazole significantly blocks gastric lesions at lower dose (2.5 mg/kg) without inhibiting acid secretion, suggesting an independent mechanism for its antiulcer effect. Time course studies on gastroprotection and acid reduction also indicate that omeprazole almost completely blocks lesions at 1 h when acid inhibition is partial. The severity of lesions correlates well with the increased level of endogenous hydroxyl radical (.OH), which when scavenged by dimethyl sulfoxide causes around 90% reduction of the lesions, indicating that .OH plays a major role in gastric damage. Omeprazole blocks stress-induced increased generation of .OH and associated lipid peroxidation and protein oxidation, indicating that its antioxidant role plays a major part in preventing oxidative damage. Omeprazole also prevents stress-induced DNA fragmentation, suggesting its antiapoptotic role to block cell death during ulceration. The oxidative damage of DNA by .OH generated in vitro is also protected by omeprazole or its analogue, lansoprazole. Lansoprazole when incubated in a .OH-generating system scavenges .OH to produce four oxidation products of which the major one in mass spectroscopy shows a molecular ion peak at m/z 385, which is 16 mass units higher than that of lansoprazole (m/z 369). The product shows no additional aromatic proton signal for aromatic hydroxylation in 1H NMR. The product absorbing at 278 nm shows no alkaline shift for phenols, thereby excluding the formation of hydroxylansoprazole. The product is assigned to lansoprazole sulfone formed by the addition of one oxygen atom at the sulfur center following attack by the .OH. Thus, omeprazole plays a significant role in gastroprotection by acting as a potent antioxidant and antiapoptotic molecule.

Original languageEnglish
Pages (from-to)10993-11001
Number of pages9
JournalJournal of Biological Chemistry
Volume278
Issue number13
DOIs
Publication statusPublished - Mar 28 2003

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Omeprazole
Scavenging
Stomach Ulcer
Hydroxyl Radical
Antioxidants
Lansoprazole
Acids
Stomach
Oxidation
Hydroxylation
Time and motion study
Phenols
DNA
Pylorus
DNA Fragmentation
Cell death
Dimethyl Sulfoxide
Sulfur
Indomethacin
Lipid Peroxidation

ASJC Scopus subject areas

  • Biochemistry

Cite this

Biswas, K., Bandyopadhyay, U., Chattopadhyay, I., Varadaraj, A., Ali, E., & Banerjee, R. K. (2003). A novel antioxidant and antiapoptotic role of omeprazole to block gastric ulcer through scavenging of hydroxyl radical. Journal of Biological Chemistry, 278(13), 10993-11001. https://doi.org/10.1074/jbc.M210328200

A novel antioxidant and antiapoptotic role of omeprazole to block gastric ulcer through scavenging of hydroxyl radical. / Biswas, Kaushik; Bandyopadhyay, Uday; Chattopadhyay, Ishita; Varadaraj, Archana; Ali, Esahak; Banerjee, Ranajit K.

In: Journal of Biological Chemistry, Vol. 278, No. 13, 28.03.2003, p. 10993-11001.

Research output: Contribution to journalArticle

Biswas, K, Bandyopadhyay, U, Chattopadhyay, I, Varadaraj, A, Ali, E & Banerjee, RK 2003, 'A novel antioxidant and antiapoptotic role of omeprazole to block gastric ulcer through scavenging of hydroxyl radical', Journal of Biological Chemistry, vol. 278, no. 13, pp. 10993-11001. https://doi.org/10.1074/jbc.M210328200
Biswas, Kaushik ; Bandyopadhyay, Uday ; Chattopadhyay, Ishita ; Varadaraj, Archana ; Ali, Esahak ; Banerjee, Ranajit K. / A novel antioxidant and antiapoptotic role of omeprazole to block gastric ulcer through scavenging of hydroxyl radical. In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 13. pp. 10993-11001.
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