Kathryn T Knecht

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Free radical products have previously been detected in rodents after chronic feeding with an ethanol-containing, high-fat diet. The significance of reactive free radical formation in ethanol-induced hepatotoxicity has been difficult to assess because most rodent models exhibit only fatty liver. However, serious hepatic damage resembling clinical alcoholic(More)
The purpose of this study was to evaluate the role of Kupffer cell activation in the pathogenesis of reperfusion injury. In a blood-free liver perfusion model, pericentral hypoxia and reperfusion injury occurred. Lactate dehydrogenase (LDH) and malondialdehyde (MDA) release, oxygen uptake, and trypan blue staining were assessed. Within the first 10 min of(More)
Alcohol treatment results in increases in the release of endotoxin from gut bacteria and membrane permeability of the gut to endotoxin, or both. Females are more sensitive to these changes. Elevated levels of endotoxin activate Kupffer cells to release substances such as eicosanoids, TNF-alpha and free radicals. Prostaglandins increase oxygen uptake and(More)
The formation of alpha-hydroxyethyl radical from ethanol by deermouse microsomes supplemented with NADPH has been demonstrated with the EPR technique of spin trapping with alpha-(4-pyridyl-1-oxide)-N-t-butylnitrone (POBN) as the spin trap, in the presence of deferoxamine mesylate. Superoxide dismutase prevented the formation of the radical adduct of the(More)
Free radical metabolism of ethanol has been suggested as a factor in its hepatotoxicity. Although evidence of lipid radical formation due to ethanol treatment in vivo has been reported, free radicals from ethanol itself have not been detected in living animals. However, by applying the EPR spectroscopy technique of spin trapping to the study of(More)
Heterocyclic aromatic amines, derived from the pyrolysis of amino acids and proteins, are potent mutagens in the Ames Salmonella assay with rodent liver activation. Additionally, heterocyclic aromatic amines are multipotent carcinogens. We report evidence that these compounds are substrates for the hydroperoxidase activity of prostaglandin H synthase, as(More)
Carbon tetrachloride and bromotrichloromethane are both metabolized by cytochrome P-450 in the presence of phenyl-N-t-butyl nitrone PBN) to the PBN/trichloromethyl (PBN/.CCl3) and the PBN carbon dioxide anion (PBN/.CO2-) radical adducts in the liver. The formation of the latter but not the former species in perfused liver was reduced markedly by prior(More)
Previous research from this laboratory using a continuous enteral ethanol (EtOH) administration model demonstrated that Kupffer cells are pivotal in the development of EtOH-induced liver injury. When Kupffer cells were destroyed using gadolinium chloride (GdCl3 ) or the gut was sterilized with polymyxin B and neomycin, early inflammation due to EtOH was(More)