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Chapter category: Ischemia-Reperfusion
Interactions of Superoxide, Nitric Oxide and Superoxide Dismutase in Gastrointestinal Damage by Nonsteroidal Anti-inflammatory Drugs and Other Agents
Chapter authors:
Brendan J. R. Whittle and Dominique Lamarque
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Mucosal injury to the gastrointestinal tract by nonsteroidal anti-inflammatory drugs
(NSAIDs) is brought about by complex and multiple mechanisms that can involve
the local production and actions of reactive oxygen species. Local infusion of superoxide
generating mixtures, as well as high local doses of nitric oxide (NO) donors, can cause
extensive gastric injury, events attenuated by radical scavengers and superoxide distmutase.
Inhibition of cyclo-oxygenase (COX), which is predominantly the COX-1 isoform in the gastric
mucosa, by NSAIDs initiates detrimental microvascular events, including a reduced blood
flow and the adherence of neutrophils, a rich cellular source of reactive oxygen radicals, that are
involved in the mucosal injury. NSAIDs also cause chronic lesions in the small intestine, which
result from initial COX inhibition, with subsequent translocation of indigenous bacteria, induction
of NO synthase and subsequent production of the cytotoxic moiety, peroxynitrite
from NO and superoxide. Agents that can scavenge superoxide or peroxynitrite or promote
their decomposition can thus attenuate such gastro-intestinal injury.
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