Involvement of oxidative stress in the impairment in biliary secretory function induced by intraperitoneal administration of aluminum to rats.
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.
Gonzalez
Marcela A
MA
Cátedra de Fisiología Humana, Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Paraje El Pozo, Santa Fe, Argentina.
Alvarez
Maria Del Lujan
Mdel L
Pisani
Gerardo B
GB
Bernal
Claudio A
CA
Roma
Marcelo G
MG
Carrillo
María C
MC
D000535:Aluminum / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D000536:Aluminum Hydroxide / Q000494:pharmacology; D000818:Animals; D002374:Catalase / Q000378:metabolism; D002779:Cholestasis; D005978:Glutathione / Q000378:metabolism; D007274:Injections, Intraperitoneal; D015227:Lipid Peroxidation; D008099:Liver / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D017392:Thiobarbituric Acid Reactive Substances; D014810:Vitamin E / Q000378:metabolism
D017392:Thiobarbituric Acid Reactive Substances; D014810:Vitamin E; D000536:Aluminum Hydroxide; D000535:Aluminum; D002374:Catalase; D005978:Glutathione