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

Abstract

We have shown that aluminum (Al) 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, three times a week, for 90 d). Vitamin E (600 mg/kg body weight) was coadministered, sc. Al increased lipid peroxidation (+50%) and decreased hepatic glutation levels (-43%) and the activity of glutation peroxidase (-50%) and catalase (-88%). Vitamin E counteracted these effects total or partially. Both plasma and hepatic Al 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 Altreated 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 Al and that vitamin E counteracts these harmful effects not only by preventing free-radical formation but also by favoring Al disposal.

Effects of Aluminium Chloride Exposure on the Histology of the Liver of Adult Wistar Rats

“…The deposition of aluminium in non nervous organs and its subsequent effects are less known. It was previously described that the effects of aluminium in the rat kidney and liver, where it induces lysosomal activation, increases iron deposition [27] and hence the liver was involved in aluminum absorption and excretion through biliary flux [28].…”

Effects of aluminium sulphate in the mouse liver: Similarities to the aging process

“…So here we focused again on the liver due to its involvement in Al absorption and excretion through biliary flux (Gonzales et al, 2007). Once in the liver Al increases cells' iron uptake and oxidative status (Perez et al, 2005).…”

Hepatitis B vaccine induces apoptotic death in Hepa1–6 cells

“…In the liver, aluminum accumulation leads to pathophysiological damage, particularly to the bile duct, and increases alkaline phosphatase levels, a marker of hepatotoxicity [25]. Aluminum has also been reported to induce cholestasis, hepatocellular damage, and impair liver transport function [26].…”