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Pharmacologic approach to tissue injury mediated by free radicals and other reactive oxygen metabolites
P M Reilly1, H J Schiller, G B Bulkley
1Department of Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Abstract:
Highly toxic metabolites of oxygen are generated normally by aerobic metabolism in most cells, and this generation is often greatly increased in pathologic conditions. When this oxidant flux exceeds the capability of the multiple endogenous antioxidant mechanisms, tissue injury ensues. The pharmacologic modification of this injury process, with agents that scavenge these reactive oxygen metabolites, block their generation, or enhance the endogenous antioxidant capability, has shown great promise in animal models of common clinical conditions, and has already been successfully applied in controlled clinical trials. This approach represents an interruption of tissue injury at its most basic level.
Insights
Pharmacologic interventions targeting reactive oxygen metabolites show promise in preventing tissue injury caused by oxidative stress. By scavenging or blocking these toxins, or boosting antioxidant defenses, this approach offers a fundamental way to interrupt cellular damage.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Aerobic metabolism generates toxic reactive oxygen metabolites.
- Pathologic conditions can significantly increase oxidant production.
- Overwhelming endogenous antioxidant mechanisms leads to tissue injury.
Purpose of the Study:
- To explore pharmacologic strategies for mitigating tissue injury.
- To investigate agents that counteract reactive oxygen metabolites.
Main Methods:
- Utilizing agents that scavenge reactive oxygen metabolites.
- Employing agents that block the generation of reactive oxygen metabolites.
- Enhancing endogenous antioxidant capabilities.
Main Results:
- Pharmacologic modification shows promise in animal models.
- Successful application demonstrated in controlled clinical trials.
Conclusions:
- Targeting reactive oxygen metabolites offers a fundamental approach to interrupting tissue injury.
- Pharmacologic interventions represent a promising strategy for managing oxidative stress-related damage.