Vaughn Price

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Acetaminophen is a mild analgesic and antipyretic agent that is safe and effective when taken in therapeutic doses. Ingestion of overdoses, however, may lead to acute liver failure accompanied by centrilobular degeneration and necrosis. Although the toxicity of acetaminophen is generally thought to be caused by direct interaction of its reactive metabolites(More)
High doses of 3-hydroxyacetanilide (3HAA), a structural isomer of acetaminophen, do not produce hepatocellular necrosis in normal male hamsters or in those sensitized to acetaminophen-induced liver damage by pretreatment with a combination of 3-methylcholanthrene, borneol, and diethyl maleate. Although 3HAA was not hepatotoxic, the administration of(More)
Coadministration of caffeine (CAF) with acetaminophen (ACM) to mice prolonged the blood half-life of ACM, increased moderately the fraction of ACM excreted as the glucuronide conjugate, and decreased slightly the fraction excreted as the sulfate conjugate. CAF exerted more profound effects on fractions of ACM metabolites which are formed as a consequence of(More)
The effects of an acute fast on acetaminophen metabolism and hepatotoxicity were investigated in male Long Evans Hooded rats. Histologic studies confirmed that fasting potentiated acetaminophen-induced hepatic necrosis. The previous known fasting-induced decrease in hepatic levels of glutathione and depletion of glycogen levels were also confirmed.(More)
The effects of insulin-deficient diabetes on acetaminophen-induced hepatotoxicity and metabolism were investigated in streptozotocin-treated male rats. Diabetic rats were less susceptible to acetaminophen-induced liver injury than normal rats. The protective effect was reversed by the administration of insulin. Diabetic rats metabolized acetaminophen at a(More)
The mechanism by which an acute fast decreases the glucuronidation of hepatotoxic doses of acetaminophen in the rat was examined. Fasting did not depress the level of the enzyme, glucuronyl transferase, or the basal level of the co-substrate, UDP-glucuronic acid (UDPGA). Administration of a hepatotoxic dose of acetaminophen rapidly depleted UDPGA levels in(More)
The effect of an acute fast on susceptibility to acetaminophen-induced hepatotoxicity was investigated in male Golden Syrian hamsters. Overnight starvation markedly elevated hepatic levels of glutathione throughout the diurnal cycle (peak concentration: 10.6 +/- 0.06 mM vs 7.3 +/- 0.3mM in controls). However, despite this apparent increase in the(More)
Previous studies in rats have shown that an acute fast decreases the apparent rate constant for glucuronidation of hepatotoxic doses of acetaminophen which results in a prolongation of the mean residence time of the drug in the animals and, hence, increased acetaminophen reactive metabolite formation and liver injury. Since acetaminophen glucuronidation(More)
The effects of streptozotocin (STZ)-induced diabetes on acetaminophen metabolism and hepatotoxicity in male Sprague-Dawley (SD) and Long Evans Hooded (LEH) rats were compared. In agreement with earlier studies, normal SD rats were more resistant to acetaminophen-induced hepatic necrosis than normal LEH rats. In contrast to LEH rats, the diabetic state did(More)
Cysteine is required for the synthesis of cosubstrates for two pathways of acetaminophen metabolism: 3'-phosphoadenosine-5'-phosphosulfate (PAPS) for sulfation and glutathione (GSH) for detoxification of the reactive metabolite (N-acetyl-p-benzoquinoneimine, NAPQI). Dietary deficiency of cysteine may reduce hepatic production of PAPS and GSH and thereby(More)