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
City
State
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Mason, Ronald Paul (2016) Imaging free radicals in organelles, cells, tissue, and in vivo with immuno-spin trapping. Redox Biol 8:422-9
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 53:2983-94
Towner, R A; Smith, N; Saunders, D et al. (2015) In vivo targeted molecular magnetic resonance imaging of free radicals in diabetic cardiomyopathy within mice. Free Radic Res 49:1140-6
Coutinho de Souza, Patricia; Smith, Nataliya; Atolagbe, Oluwatomisin et al. (2015) OKN-007 decreases free radical levels in a preclinical F98 rat glioma model. Free Radic Biol Med 87:FRBMD1500130
Taetzsch, Thomas; Levesque, Shannon; McGraw, Constance et al. (2015) Redox regulation of NF-κB p50 and M1 polarization in microglia. Glia 63:423-40
Shvedova, A A; Kisin, E R; Murray, A R et al. (2014) ESR evidence for in vivo formation of free radicals in tissue of mice exposed to single-walled carbon nanotubes. Free Radic Biol Med 73:154-65
Kumar, Ashutosh; Chen, Shih-Heng; Kadiiska, Maria B et al. (2014) Inducible nitric oxide synthase is key to peroxynitrite-mediated, LPS-induced protein radical formation in murine microglial BV2 cells. Free Radic Biol Med 73:51-9
Das, Suvarthi; Kumar, Ashutosh; Seth, Ratanesh Kumar et al. (2013) Proinflammatory adipokine leptin mediates disinfection byproduct bromodichloromethane-induced early steatohepatitic injury in obesity. Toxicol Appl Pharmacol 269:297-306
Chatterjee, Saurabh; Ganini, Douglas; Tokar, Erik J et al. (2013) Leptin is key to peroxynitrite-mediated oxidative stress and Kupffer cell activation in experimental non-alcoholic steatohepatitis. J Hepatol 58:778-84
Ranguelova, Kalina; Rice, Annette B; Lardinois, Olivier M et al. (2013) Sulfite-mediated oxidation of myeloperoxidase to a free radical: immuno-spin trapping detection in human neutrophils. Free Radic Biol Med 60:98-106

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