1979
DOI: 10.1016/0009-2797(79)90129-7
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The nephrotoxicity of p-aminophenol. II. The effect of metabolic inhibitors and inducers

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Cited by 61 publications
(18 citation statements)
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“…This observed toxicity is entirely in agreement with our 28-day study results, although the actual daily intake in the diet study was not given. A structural isomer, 4-aminophenol is a major metabolite of the analgesic and antipyretic drug, acetaminophen, and is known to exert renal toxicity (Green et al, 1969;Calder et al, 1979). Mechanistic studies in rats suggest that 4-aminophenol may be oxidized to benzoquinoneimine and then conjugated with glutathione in the liver to be excreted in the bile, and subsequently reabsorbed and transported via the systemic circulation to the kidney, where toxic effects occur (Garland et al, 1990).…”
Section: Discussionmentioning
confidence: 99%
“…This observed toxicity is entirely in agreement with our 28-day study results, although the actual daily intake in the diet study was not given. A structural isomer, 4-aminophenol is a major metabolite of the analgesic and antipyretic drug, acetaminophen, and is known to exert renal toxicity (Green et al, 1969;Calder et al, 1979). Mechanistic studies in rats suggest that 4-aminophenol may be oxidized to benzoquinoneimine and then conjugated with glutathione in the liver to be excreted in the bile, and subsequently reabsorbed and transported via the systemic circulation to the kidney, where toxic effects occur (Garland et al, 1990).…”
Section: Discussionmentioning
confidence: 99%
“…Calder, in a series of papers (Calder et al, 1975(Calder et al, , 1979, has shown that PAP is highly nephrotoxic in acute experiments. His group proposed it as a "model" for the study of nephrotoxicity but presumed that PAP itself was not directly involved in the human disease of chronic abuse, apparently for two reasons-first, that after acute dosage lesions were limited to the kidney cortex, and second, that PAP had not been reported as a metabolite of either phenacetin or APAP.…”
Section: Identification Of Reactive Metabolite(s} a N-hydroxy Acetammentioning
confidence: 97%
“…This reaction has been denied in the literature to date but has been demonstrated in the studies reported here. As a hypothesis, it might be proposed that AP AP is deacetylated within the kidney to PAP and that the PAP thus formed has at least three possible fates: (1) to be reacetylated back to AP AP (Smith and Williams, 1949); (2) to be covalently bound to kidney protein (Calder et al, 1979); and (3) to undergo phenolic conjugation and thereby to be excreted at a high rate (Smith and Williams, 1949). …”
Section: Implications Of the Reactive Metabolite Hypothesismentioning
confidence: 98%
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“…Nephrotoxicity of para-aminophenol (PAP) is associated with proximal tubular necrosis, and increases in blood urea nitrogen (BUN) concentration and kidney weight within 24 hr following ip administration (300 mg/kg) (Calder et al, 1979;Newton et al, 1983;Gartland et al, 1989;Tarloff et al, 1989;Shao and Tarloff, 1996). At early times (2-4 hr) following PAP administration, we observed decreases in renal nonprotein sulfhydryl (NPSH) content, oxygen consumption, and adenine nucleotide concentrations (Shao and Tarloff, 1996).…”
mentioning
confidence: 88%