Effects of biliary cannulation and buthionine sulphoximine pretreatment on the nephrotoxicity of para-aminophenol in the Fischer 344 rat.
The effects of a glutathione depletor, buthionine sulphoximine (BSO) and biliary cannulation on the nephrotoxicity of p-aminophenol (PAP) have been investigated in the F344 rat. Pretreatment with BSO completely protected against the nephrotoxicity of a 50 mg/kg dose of PAP, assessed by clinical chemistry, renal histopathology, and 1H-NMR urinalysis. Biliary cannulation partially protects against nephrotoxicity induced by 100 mg/kg PAP. These data suggest that the nephrotoxicity of PAP may be due in part to the formation of a proximate toxic metabolite in the liver which is excreted in the bile, subsequently reabsorbed and transported via the systemic circulation to the kidney where the toxic effects occur.
Gartland
K P
KP
Department of Chemistry, Birkbeck College, University of London, UK.
Eason
C T
CT
Bonner
F W
FW
Nicholson
J K
JK
D000627:Aminophenols / Q000633:toxicity*; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology*; D001659:Biliary Tract; D019328:Buthionine Sulfoximine; D002404:Catheterization; D005978:Glutathione / Q000502:physiology; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced*; D008099:Liver / Q000502:physiology; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011522:Protons; D051381:Rats; D011916:Rats, Inbred F344
D000627:Aminophenols; D000963:Antimetabolites; D011522:Protons; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D005978:Glutathione; C026729:4-aminophenol