We have set research priorities to focus on free radical generation in animal models of disease and toxicity for which there is a strong indication of an environmental component. The ways in which environmental agents increase disease risks and toxicity are still poorly understood. In the past our work has been concentrated on the in vivo formation and detection of free radicals from toxic metals and organic compounds and extended into investigations of free radical formation during inflammation caused by lipopolysaccharide itself and in combination with diesel exhaust particles. It is now continued into studies of environmental exotoxins and pathogens with the aim of understanding the basic free radical mechanisms involved in distinctive organ infections, immune disease, and obesity. In vivo spin trapping has been the most successful method for the detection of highly reactive free radical molecules in vivo. The group continued to use spin trapping to solve in vitro biochemical and in vivo toxicological disease problems by using two major approaches for spin trapping, with either ESR detection or antibody recognition and MS identification of the trapped radical. By the use of in vivo spin-trapping methods, these studies test the hypotheses that: 1) free radicals are causative molecules in the complex pathogenesis of lung infections, obesity and allergic response;and 2) specific biochemical pathways are involved in triggering generation of free radicals that may act as mediators and/or modulators of inflammatory reactions associated with human immunity and disease response. Free radical generation in vivo caused by the bacterial pathogen Pseudomonas aeruginosa, superantigen staphylococcal enterotoxin B, the endotoxin LPS, obesity, CCl4, and sulfites has been shown in specific states of lung inflammation, steatohepatitis, and allergic response.
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