Abstract

Introduction

Hydroxyl radicals

Toxic aldehydes

Acyloins

DOX-induced
cardiotoxicity

Complex I
deficiency

Hypoxic-ischemic
encephalopathy

Summary
& conclusions

References

Discussion
Board

The production of free radicals leads to lipid peroxidation, and is a major contributor to several types of toxic injury. Products of lipid peroxidation play a significant role in aging, drug toxicity, and in the pathophysiology of a number of human diseases such as atherosclerosis, cancer and heart disease. The study of oxidative stress in biological systems requires markers that allow correlations to be established between injury and the products of lipid peroxidation. Our laboratory has developed methods using GC/MS techniques for measuring in-vivo levels of hydroxyl radicals, cytotoxic aldehydes and acyloins (breakdown products of aldehyde metabolism). We used these methods to determine the role of free radicals in the development of oxidative injury in several animal models of disease. Experimental evidence will be presented to support the conclusions below regarding the relationship between free radical production and tissue injury. Our data indicate that free radicals and byproducts of lipid peroxidation can be measured with good precision and accuracy both in plasma and in tissues. Several generalizations can be made about the nature of oxidative injury, and the usefulness of measuring hydroxyl radicals and other reactive oxygen species.

• We have shown that increases in the production of aldehydes, hydroxyl radicals and acyloins are excellent markers of cytotoxic injury.
• Levels of aldehydes, free radicals and acyloins change rapidly in-vivo, making it possible to monitor physiologically significant changes over short periods of time. This allows the study of the mechanisms of free radical-mediated oxidative injury.
• Free radical production appears to be an early biochemical event, which often precedes functional or histological evidence of tissue injury.
• Free radicals are important contributors in the cascade of events that leads to cell death by apoptosis or necrosis.

In our experiments apoptotic cell death could be prevented even when significant increases in free radicals occurred. These interventions appear to have blocked steps that were distal to free radical production in the cascade of events leading to cell death. The availability of methods such as those developed by our laboratory has made the study of biochemical changes associated with free radical-mediated tissue injury possible.

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Presentation Number SAlehotay0666
Keywords: hydroxyl radicals, aldehydes, acyloins, doxorubicin, carnitine, cardiomyopathy, complex I deficiency