Lipid and protein oxidation in hepatic homogenates and cell membranes exposed to bile acids.
Cholestasis occurs in a variety of hepatic diseases and causes damage due to accumulation of bile acids in the liver. The aim was to investigate the effect of several bile acids, i.e. chenodeoxycholic, taurochenodeoxycholic, deoxycholic, taurodeoxycholic, ursodeoxycholic, lithocholic and taurolithocholic (TLC), in inducing oxidative damage. Hepatic tissue of male Sprague-Dawley rats was incubated with or without 1 mM of each bile acid, with or without 0.1 mM FeCl(3) and 0.1 mM ascorbic acid for the purpose of generating free radicals. Several bile acids increased lipid and protein oxidation, with TLC being the most pro-oxidative (657% and 175% in homogenates and 350% and 311% in membranes, respectively). TLC also enhanced iron-induced oxidative stress to lipids (21% in homogenates and 29% in membranes) and to proteins (74% in membranes). This enhancement was dose- and time-dependent and was reduced by melatonin. These results suggest that bile acids differentially mediate hepatic oxidative stress and may be involved in the physiopathology of cholestasis.
Fuentes-Broto
Lorena
L
Department of Pharmacology and Physiology, University of Zaragoza, Spain.
Martínez-Ballarín
Enrique
E
Miana-Mena
Javier
J
Berzosa
Cesar
C
Piedrafita
Eduardo
E
Cebrián
Igor
I
Reiter
Russel J
RJ
García
Joaquín J
JJ
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001647:Bile Acids and Salts / Q000378:metabolism / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002779:Cholestasis / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008550:Melatonin / Q000494:pharmacology; D008565:Membrane Proteins / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley
D000975:Antioxidants; D001647:Bile Acids and Salts; D008565:Membrane Proteins; D008550:Melatonin