Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
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Gene/Protein
Disease
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Target Concepts:
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Query: UMLS:C0033687 (
proteinuria
)
24,015
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Aminophenols and halogenated anilines induce nephrotoxicity and mild hepatotoxicity in rats. In this study, the in vivo and in vitro nephrotoxic potential of
4-amino-2-chlorophenol
and 2-amino-4-chlorophenol, monochlorinated aminophenols and potential metabolites of 3-chloroaniline, was evaluated. Hepatotoxicity of both compounds was also examined in vivo. Male Fischer 344 rats (four/group) were administered
4-amino-2-chlorophenol
hydrochloride (0.4, 0.8 or 1.0 mmol/kg), 2-amino-4-chlorophenol hydrochloride (0.4, 0.8 or 1.2 mmol/kg) or vehicle intraperitoneally (i.p.) and renal and hepatic function monitored for 48 h. Administration of
4-amino-2-chlorophenol
(0.8 mmol/kg) induced nephrotoxicity, while only minor changes in kidney function were observed following administration of 0.4 mmol/kg of
4-amino-2-chlorophenol
or 0.8 mmol/kg of 2-amino-4-chlorophenol. Increasing the dose of
4-amino-2-chlorophenol
to 1.0 mmol/kg or 2-amino-4-chlorophenol to 1.2 mmol/kg resulted in lethality. Nephrotoxicity induced by
4-amino-2-chlorophenol
was characterized by diuresis, increased
proteinuria
, glucosuria, hematuria, elevated blood urea nitrogen (BUN) concentration and kidney weight, and marked proximal tubular damage, while 2-amino-4-chlorophenol induced milder effects on renal function and transient oliguria instead of diuresis. No hepatotoxicity was observed with either compound at any dose tested. In the in vitro studies, the direct effects of
4-amino-2-chlorophenol
or 2-amino-4-chlorophenol on organic ion accumulation, pyruvate-stimulated gluconeogenesis and lactate dehydrogenase (LDH) leakage were determined using renal cortical slices. 4-Amino-2-chlorophenol and 2-amino-4-chlorophenol were almost equally effective in inhibiting organic anion or cation uptake and gluconeogenesis or increasing LDH leakage, although small differences in the minimum effective concentrations were present (minimum effective concentration, 0.01-0.5 mM range). These results demonstrate that
4-amino-2-chlorophenol
is a more potent nephrotoxicant than 2-amino-4-chlorophenol in vivo. The results also indicate that the addition of a chloride group to aminophenols enhances renal toxicity.
...
PMID:Nephrotoxicity of 4-amino-2-chlorophenol and 2-amino-4-chlorophenol in the Fischer 344 rat. 865 59
