Modulation of taurine levels in the rat liver alters methylene dianiline hepatotoxicity.
Methylene dianiline (DAPM) causes hepatic damage and bile duct necrosis in rats. This has been detected histologically and biochemically. The toxicity was dose related over the range 0-100 mg/kg but the dose response relationship showed a maximum at about 75-100 mg/kg. This was true for both histopathology and biochemical parameters of liver dysfunction. When animals were depleted of taurine using beta-alanine pretreatment, the toxicity of DAPM was increased. Conversely treatment of rats with taurine, significantly attenuated the rise in alanine transaminase (ALT). However depletion of taurine with guanidinoethanesulphonate (GES) attenuated rises in both transaminases. It is concluded that taurine may play a role in the toxicity of DAPM but that GES, although depleting taurine as does beta-alanine, causes additional effects such as increasing glutathione (GSH), perhaps leading to protection.
Seabra
V
V
Department of Toxicology, School of Pharmacy, University of London, UK.
Timbrell
J A
JA
D000814:Aniline Compounds / Q000633:toxicity*; D000818:Animals; D001652:Bile Ducts / Q000187:drug effects / Q000473:pathology; D002273:Carcinogens / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013654:Taurine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D000637:Transaminases / Q000097:blood; D015091:beta-Alanine / Q000494:pharmacology; D001559:Benzhydryl Compounds
D000814:Aniline Compounds; D002273:Carcinogens; D013654:Taurine; D000637:Transaminases; D015091:beta-Alanine; C009558:taurocyamine; C009505:4,4'-diaminodiphenylmethane; D001559:Benzhydryl Compounds