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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)
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)
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)
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)
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)
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)
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)
Alcohol ingestion results in increases in the release of endotoxin from gut bacteria or membrane permeability of the gut to endotoxin, or both. Female rats are more sensitive to these changes. Elevated levels of endotoxin activate Kupffer cells to release substances such as eicosanoids, tumor necrosis factor-alpha and free radicals. Prostaglandins increase(More)
Kupffer cells have been implicated in mechanisms of pathophysiology following liver transplantation. Recently, postoperative injury in ethanol-induced fatty liver has been evaluated because fatty livers often fail following transplantation. The low-flow, reflow liver perfusion model was used to study the role of Kupffer cells (KC) in reperfusion injury to(More)