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A Novel Antioxidant and Antiapoptotic Role of Omeprazole to Block Gastric Ulcer through Scavenging of Hydroxyl Radical

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Title A Novel Antioxidant and Antiapoptotic Role of Omeprazole to
Block Gastric Ulcer through Scavenging of Hydroxyl Radical
 
Creator Biswas, Kaushik
Bandyopadhyay, Uday
Chattopadhyay, Ishita
Varadaraj, Archana
Ali, Esahak
Banerjee, Ranajit K
 
Subject Cell Biology & Physiology
Infectious Diseases and Immunology
 
Description 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.
 
Publisher American Society for Biochemistry and Molecular Biology
 
Date 2003
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/608/1/JOURNAL_OF_BIOLOGICAL_CHEMISTRY%2C278(13)%2C_10993%2D11001[74].pdf
Biswas, Kaushik and Bandyopadhyay, Uday and Chattopadhyay, Ishita and Varadaraj, Archana and Ali, Esahak and Banerjee, Ranajit K (2003) A Novel Antioxidant and Antiapoptotic Role of Omeprazole to Block Gastric Ulcer through Scavenging of Hydroxyl Radical. The Journal of Biological Chemistry, 278 (13). pp. 10993-11000.
 
Relation http://dx.doi.org/10.1074/jbc.M210328200
http://www.eprints.iicb.res.in/608/