These studies on oxygen toxicity in the red cell rely on the use of xenobiotic agents as biochemical probes. The overall approach is to study the interaction of a xenobiotic agent with oxygen and with red cell components such as hemoglobin or the red cell membrane and ultimately extend these studies to the red cell. Experimental protocols are designed to answer questions of red cell structure, function and toxicity.
The aims are (1) to study changes in the metabolic and structural characteristics of the red cell induced by oxidative stress (2) to elucidate mechanisms by which the red cell maintains its reducing environment and (3) to characterize the molecular mechanism of the interaction of xenobiotics and oxygen with the objective of relating it to red cell oxygen toxicity. In this proposal we present studies (1) to elucidate the mechanism by which hemin, a breakdown product of hemoglobin during oxidative stress, affects red cell integrity (2) to understand the mechanism of red cell toxicity of vanadium compounds that react with oxygen (3) to characterize the physiological role of plasma constituents in the metabolic response of the red cell to oxidative stress. Our diversified approach has allowed us to develop model systems that contribute to our knowledge of oxygen cytotoxicity and has provided the opportunity of probing red cell metabolism and structure with xenobiotics to determine both the physiological function of the red cell and its behavior under conditions of mild oxidative stress.
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