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We examined the retinal ganglion cell layer of the dromedary camel, Camelus dromedarius. We have estimated that there are 8 million neurons in the ganglion cell layer of this large retina (mean area of 2,300 mm(-2)). However, only approximately 1 million are considered to be ganglion cells. The ganglion cells are arranged as two areas of high cell density,(More)
The effects of N-acetylcysteine (NAC), 2-mercaptopropionylglycine (MPG) and dithiothreitol (DTT) on the metabolism and toxicity of acetaminophen (APAP) were examined in isolated mouse hepatocytes maintained in primary culture on collagen-coated dishes. Both NAC and MPG increased the formation of the glutathione and sulfate conjugates of APAP and decreased(More)
Exposure of isolated mouse hepatocytes to a toxic concentration of acetaminophen (5 mM) resulted in damage to the mitochondrial respiratory apparatus. The nature of this damage was investigated by measuring respiration stimulated by site-specific substrates in digitonin-permeabilized hepatocytes after acetaminophen exposure. Respiration stimulated by(More)
The killing of isolated hepatocytes by N-acetyl-p-benzoquinone imine (NAPQI), the major metabolite of the oxidation of the hepatotoxin acetaminophen, has been studied previously as a model of liver cell injury by the parent compound. Such studies assume that the toxicity of acetaminophen is mediated by NAPQI and that treatment with exogenous NAPQI(More)
Studies were conducted in mice to examine the origin and fate of the amino acid-containing conjugates of acetaminophen (APAP). Collection of bile containing [14C]APAP metabolites (mainly the glutathione conjugate) in common duct-cannulated mice given a 250 mg/kg oral dose of the drug reduced by greater than 70% the urinary excretion of the cysteine and(More)
It has been proposed that a number of chemical-induced cell injuries result from disruption of the ability of the cell to control calcium. Many of the techniques used to develop this theory have relied on indirect measurements of intracellular calcium. The advent of digital imaging fluorescence microscopy has allowed a more direct examination of the(More)
The effect of acetaminophen (APAP) exposure on the formation of oxidized glutathione (GSSG) was investigated in cultured mouse hepatocytes to determine if oxidative damage is involved in the toxicity of this drug. Incubations of hepatocytes for 24 hr with 1 mM APAP produced a time-dependent loss of cell viability which was preceded by depletion of reduced(More)
A high-performance liquid chromatographic method for analysis of acetaminophen and its conjugated metabolites in tissues was developed and used to determine tissue, plasma and urine levels of the drug and its glucuronic acid, sulfate, glutathione, cysteine mercapturic acid conjugates in mice given a 500 mg/kg oral dose of [14C]acetaminophen. Peak levels of(More)
A hamster hepatocyte system was developed for use in studying the toxicity of acetaminophen (APAP). The cells were isolated and placed in culture conditions in petri dishes containing a film of collagen. Hepatocytes, after attachment to collagen, were exposed for various periods of time to different concentrations of APAP. Hepatocytes exposed to APAP(More)
It has been suggested that elevated cytosolic free calcium plays a key role in acetaminophen-induced cell death. The present study has examined the effect of a toxic concentration of acetaminophen on cytosolic free calcium in single mouse hepatocytes, using the dye fura-2 and video imaging fluorescence microscopy. Cytosolic free calcium was calculated from(More)