Involvement of oxidative stress in the impairment in biliary secretory function induced by intraperitoneal administration of aluminum to rats

GONZÁLEZ, MARCELA; ALVAREZ, MARÍA DE LUJÁN; PISANI, GERARDO BRUNO; BERNAL, CLAUDIA; ROMA, MARCELO; CARRILLO, MARÍA CRISTINA

BIOLOGICAL TRACE ELEMENT RESEARCH

Humana Press

Año: 2007 vol. 116 p. 329 - 348

0163-4984

We have shown that aluminum induces cholestasis associated with multiple alterations in hepatocellular transporters involved in bile secretory function, like Mrp2. This work aims to investigate whether these harmful effects are mediated by the oxidative stress caused by the metal. For this purpose, the capability of the antioxidant agent, vitamin E, to counteract these alterations was studied in male Wistar rats. Aluminum hydroxide (or saline in controls) was administered ip (27 mg/ kg body weight, thrice a week, for 90 days). Vitamin E (600 mg/kg body weight) was coadministered, sc. Aluminum increased lipid peroxidation (+50%) and decreased hepatic glutation levels (-43%) and the activity of glutation peroxidase (-50%) and catalase (-88%). Vitamin E counteracted total or partially these effects. Both plasma and hepatic aluminum levels reached at the end of the treatment were significantly reduced by vitamin E (-40% and –44%, respectively; p<0.05). Al increased 4 times the hepatic apoptotic index, and this effect was fully counteracted by vitamin E. Bile flow was decreased in aluminum–treated rats (-37%), and restored to normality by vitamin E. The antioxidant normalized the hepatic handling of the Mrp2 substrates, rose bengal and dinitrophenyl-S-glutathione, which was causally associated with restoration of Mrp2 expression. Our data indicate that oxidative stress has a crucial role in cholestasis, apoptotic/necrotic hepatocellular damage and the impairment in liver transport function induced by aluminum, and that vitamin E counteracts these harmful effects not only by preventing free-radical formation but also by favoring aluminum disposal.