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32 results on '"Thiruchelvam, Mona"'

5. Prolonged toxicokinetics and toxicodynamics of Paraquat in Mouse Brain

Author

Prasad, Kavita, Winnik, Bozena, Thiruchelvam, Mona J., Buckley, Brian, Mirochnitchenko, Oleg, and Richfield, Eric K.

Subjects
Paraquat (Pesticide) -- Health aspects, Research, Risk factors, Reports, Health aspects, Parkinson disease -- Risk factors -- Research, Pesticides -- Health aspects -- Research -- Reports, Environmental toxicology -- Research -- Reports -- Health aspects, Brain research -- Reports -- Research -- Health aspects, Parkinson's disease -- Risk factors -- Research
Abstract

Background: Paraquat (PQ) has been implicated as a risk factor for the Parkinson disease phenotype (PDP) in humans and mice using epidemiologic or experimental approaches. The toxicokinetics (TK) and toxicodynamics [...]

Published
2007

23. Paraquat increases cyanide-insensitive respiration in murine lung epithelial cells by activating an NAD(P)H:paraquat oxidoreductase : identification of the enzyme as thioredoxin reductase

Author

Gray, Joshua P., Heck, Diane E., Mishin, Vladimir, Smith, Peter J. S., Hong, Jun-Yan, Thiruchelvam, Mona, Cory-Slechta, Deborah A., Laskin, Debra L., Laskin, Jeffrey D., Gray, Joshua P., Heck, Diane E., Mishin, Vladimir, Smith, Peter J. S., Hong, Jun-Yan, Thiruchelvam, Mona, Cory-Slechta, Deborah A., Laskin, Debra L., and Laskin, Jeffrey D.

Abstract

Author Posting. © American Society for Biochemistry and Molecular Biology, 2007. This article is posted here by permission of American Society for Biochemistry and Molecular Biology for personal use, not for redistribution. The definitive version was published in Journal of Biological Chemistry 282 (2007): 7939-7949, doi:10.1074/jbc.M611817200., Pulmonary fibrosis is one of the most severe consequences of exposure to paraquat, an herbicide that causes rapid alveolar inflammation and epithelial cell damage. Paraquat is known to induce toxicity in cells by stimulating oxygen utilization via redox cycling and the generation of reactive oxygen intermediates. However, the enzymatic activity mediating this reaction in lung cells is not completely understood. Using self-referencing microsensors, we measured the effects of paraquat on oxygen flux into murine lung epithelial cells. Paraquat (10–100 µM) was found to cause a 2–4-fold increase in cellular oxygen flux. The mitochondrial poisons cyanide, rotenone, and antimycin A prevented mitochondrial- but not paraquat-mediated oxygen flux into cells. In contrast, diphenyleneiodonium (10 µM), an NADPH oxidase inhibitor, blocked the effects of paraquat without altering mitochondrial respiration. NADPH oxidases, enzymes that are highly expressed in lung epithelial cells, utilize molecular oxygen to generate superoxide anion. We discovered that lung epithelial cells possess a distinct cytoplasmic diphenyleneiodonium-sensitive NAD(P)H:paraquat oxidoreductase. This enzyme utilizes oxygen, requires NADH or NADPH, and readily generates the reduced paraquat radical. Purification and sequence analysis identified this enzyme activity as thioredoxin reductase. Purified paraquat reductase from the cells contained thioredoxin reductase activity, and purified rat liver thioredoxin reductase or recombinant enzyme possessed paraquat reductase activity. Reactive oxygen intermediates and subsequent oxidative stress generated from this enzyme are likely to contribute to paraquat-induced lung toxicity., This work was supported in part by National Institutes of Health Grants U54AR055073, ES006897, CA100994, CA093798, ES003647, ES010791, ES004738, GM034310, RR001395, and ES005022.

Published
2009

32. Quantification of Paraquat, MPTP, and MPP+ in brain tissue using microwave-assisted solvent extraction (MASE) and high-performance liquid chromatography–mass spectrometry.

Author

Winnik, Bozena, Barr, Dana B., Thiruchelvam, Mona, Montesano, M. Angela, Richfield, Eric K., and Buckley, Brian

Subjects
PARAQUAT, ANIMAL models in research, CENTRAL nervous system, PARKINSON'S disease, LABORATORY mice, SOLVENT extraction
Abstract

Animal models, consistent with the hypothesis of direct interaction of paraquat (PQ) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) with specific areas of the central nervous system have been developed to study Parkinson’s disease (PD) in mice. These models have necessitated the creation of an analytical method for unambiguous identification and quantitation of PQ and structurally similar MPTP and 1-methyl-4-phenylpyridinium ion (MPP+) in brain tissue. A method for determination of these compounds was developed using microwave-assisted solvent extraction (MASE) and liquid chromatography–mass spectrometry. Extraction solvent and microwave conditions such as power and time were optimized to produce recoveries of 90% for PQ 78% for MPTP and 97% for its metabolite MPP+. The chromatographic separation was performed on a C8, column and detection was carried out using an ion trap as an analyzer with electrospray ionization. Mass spectrometer parameters such as heated capillary temperature, spray voltage, capillary voltage and others were also optimized for each analyte. Analysis was done in selective ion-monitoring (SIM) mode using m/ z 186 for PQ, m/ z 174 for MPTP, and m/ z 170 for MPP+. The method detection limit for paraquat in matrix was 100 pg, 40 pg for MPTP, and 20 pg MPP+. [ABSTRACT FROM AUTHOR]

Published
2009
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