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.

Project Start
Project End
Budget Start
Budget End
Support Year
23
Fiscal Year
2013
Total Cost
$626,589
Indirect Cost
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State
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van 't Erve, Thomas J; Lih, Fred B; Kadiiska, Maria B et al. (2018) Elevated plasma 8-iso-prostaglandin F2? levels in human smokers originate primarily from enzymatic instead of non-enzymatic lipid peroxidation. Free Radic Biol Med 115:105-112
Kumar, Ashutosh; Triquigneaux, Mathilde; Madenspacher, Jennifer et al. (2018) Sulfite-induced protein radical formation in LPS aerosol-challenged mice: Implications for sulfite sensitivity in human lung disease. Redox Biol 15:327-334
Ganini, Douglas; Santos, Janine H; Bonini, Marcelo G et al. (2018) Switch of Mitochondrial Superoxide Dismutase into a Prooxidant Peroxidase in Manganese-Deficient Cells and Mice. Cell Chem Biol 25:413-425.e6
Sinha, Birandra K; van 't Erve, Thomas J; Kumar, Ashutosh et al. (2017) Synergistic enhancement of topotecan-induced cell death by ascorbic acid in human breast MCF-7 tumor cells. Free Radic Biol Med 113:406-412
Sinha, Birandra K; Kumar, Ashutosh; Mason, Ronald P (2017) Nitric oxide inhibits ATPase activity and induces resistance to topoisomerase II-poisons in human MCF-7 breast tumor cells. Biochem Biophys Rep 10:252-259
Ganini, Douglas; Leinisch, Fabian; Kumar, Ashutosh et al. (2017) Fluorescent proteins such as eGFP lead to catalytic oxidative stress in cells. Redox Biol 12:462-468
van 't Erve, Thomas J; Kadiiska, Maria B; London, Stephanie J et al. (2017) Classifying oxidative stress by F2-isoprostane levels across human diseases: A meta-analysis. Redox Biol 12:582-599
Kumar, Ashutosh; Leinisch, Fabian; Kadiiska, Maria B et al. (2016) Formation and Implications of Alpha-Synuclein Radical in Maneb- and Paraquat-Induced Models of Parkinson's Disease. Mol Neurobiol 53:2983-2994
Kumar, Ashutosh; Ehrenshaft, Marilyn; Tokar, Erik J et al. (2016) Nitric oxide inhibits topoisomerase II activity and induces resistance to topoisomerase II-poisons in human tumor cells. Biochim Biophys Acta 1860:1519-27
Mason, Ronald Paul (2016) Imaging free radicals in organelles, cells, tissue, and in vivo with immuno-spin trapping. Redox Biol 8:422-9

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