A Novel Antioxidant and Antiapoptotic Role of Omeprazole to Block Gastric Ulcer through Scavenging of Hydroxyl Radical
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
View Archive Info| Field | Value | |
| Title |
A Novel Antioxidant and Antiapoptotic Role of Omeprazole to
Block Gastric Ulcer through Scavenging of Hydroxyl Radical
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| Creator |
Biswas, Kaushik
Bandyopadhyay, Uday Chattopadhyay, Ishita Varadaraj, Archana Ali, Esahak Banerjee, Ranajit K |
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| Subject |
Cell Biology & Physiology
Infectious Diseases and Immunology |
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| 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.
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| Publisher |
American Society for Biochemistry and Molecular Biology
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| Date |
2003
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| Type |
Article
PeerReviewed |
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| Format |
application/pdf
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| 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. |
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| Relation |
http://dx.doi.org/10.1074/jbc.M210328200
http://www.eprints.iicb.res.in/608/ |
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