Bile duct obstruction is not a prerequisite for type I biliary epithelial cell hyperplasia.

Biliary obstruction, produced by common bile duct ligation or alpha-naphthylisothiocyanate (ANIT) treatment in rats, has been associated with the development of type I biliary epithelial cell (BEC) hyperplasia. However, the exact mechanism(s) by which bile duct obstruction lead(s) to this proliferative lesion are not clear. The present studies were designed to determine if cholestasis, in the absence of biliary obstruction, would result in type I BEC hyperplasia.

Metabolism of tert-butylhydroquinone to S-substituted conjugates in the male Fischer 344 rat.

tert-Butyl-4-hydroxyanisole (BHA) and its demethylated analog, tert-butyl-hydroquinone (TBHQ), are antioxidants used in food. Both BHA and TBHQ have been shown to promote kidney and bladder carcinogenesis in the rat. We have previously demonstrated that glutathione (GSH) conjugates of a variety of hydroquinones are nephrotoxic and proposed that GSH conjugation serves to target these compounds to the kidney.

Biliary epithelial cell proliferation following alpha-naphthylisothiocyanate (ANIT) treatment: relationship to bile duct obstruction.

These studies were designed to evaluate the importance of bile duct obstruction in the pathogenesis of alpha-naphthylisothiocyanate (ANIT)-induced biliary epithelial cell (BEC) hyperplasia in rats. Hepatobiliary function and morphology were evaluated in adult male Sprague-Dawley rats 16, 24, 48, 72, 120, and 168 hr after a single oral dose of ANIT (0, 25, 75, or 150 mg/kg). After 75 or 150 mg/kg ANIT, multifocal bile duct obstruction was observed at 48 and 72 hr and preceded BEC hyperplasia which occurred at 120 and 168 hr.

Metabolism of 2-(glutathion-S-yl)hydroquinone and 2,3,5- (triglutathion-S-yl)hydroquinone in the in situ perfused rat kidney: relationship to nephrotoxicity.

2,3,5-(Triglutathion-S-yl)hydroquinone [2,3,5-(triGSyl)HQ] (20 mumol/kg) and 2-(glutathion-S-yl)hydroquinone [2-(GSyl)-HQ] (250 mumol/kg) both cause nephrotoxicity when administered to male rats, although the former is considerably more potent than the latter. To address the issue of the differential potency of these conjugates we investigated the metabolism and toxicity of 2,3,5-(triGSyl)HQ and 2-(GSyl)HQ in the in situ perfused rat kidney. Infusion of 5 and 10 mumol 2,3,5-(triGSyl)HQ into the right renal artery caused a time-dependent elevation in gamma-glutamyl transpeptidase (gamma-GT) excretion into urine produced by both the perfused and the contralateral kidneys.