title: Melatonin protects against taurolithocholic-induced oxidative stress in rat liver.
abstract: Cholestasis, encountered in a variety of clinical disorders, is characterized by intracellular accumulation of toxic bile acids in the liver. Furthermore, oxidative stress plays an important role in the pathogenesis of bile acids. Taurolithocholic acid (TLC) was revealed in previous studies as the most pro-oxidative bile acid. Melatonin, a well-known antioxidant, is a safe and widely used therapeutic agent. Herein, we investigated the hepatoprotective role of melatonin on lipid and protein oxidation induced by TLC alone and in combination with FeCl(3) and ascorbic acid in rat liver homogenates and hepatic membranes. The lipid peroxidation products, malondialdehyde and 4-hydroxyalkenals (MDA + 4-HDA), and carbonyl levels were quantified as indices of oxidative damage to hepatic lipids and proteins, respectively. In the current study, the rise in MDA + 4-HDA levels induced by TLC was inhibited by melatonin in a concentration-dependent manner in both liver homogenates and in hepatic membranes. Melatonin also had protective effects against structural damage to proteins induced by TLC in membranes. These results suggest that the indoleamine melatonin may potentially act as a protective agent in the therapy of those diseases that involve bile acid toxicity.
authors.affiliation: Department of Pharmacology and Physiology, Universidad de Zaragoza, Zaragoza, Spain.
authors.forename: Lorena
authors.initials: L
authors.lastname: Fuentes-Broto
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Miana-Mena
authors.forename: Eduardo
authors.initials: E
authors.lastname: Piedrafita
authors.forename: César
authors.initials: C
authors.lastname: Berzosa
authors.forename: Enrique
authors.initials: E
authors.lastname: Martínez-Ballarín
authors.forename: Francisco A
authors.initials: FA
authors.lastname: García-Gil
authors.forename: Russel J
authors.initials: RJ
authors.lastname: Reiter
authors.forename: Joaquín J
authors.initials: JJ
authors.lastname: García
mesh_terms: D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D002756:Cholagogues and Choleretics / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D005290:Ferric Compounds / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D008550:Melatonin / Q000494:pharmacology*; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D050050:Protein Carbonylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013658:Taurolithocholic Acid / Q000633:toxicity*
chemical_list: D000447:Aldehydes; D000975:Antioxidants; D002712:Chlorides; D002756:Cholagogues and Choleretics; D005290:Ferric Compounds; D008315:Malondialdehyde; D013658:Taurolithocholic Acid; D008550:Melatonin; C027576:4-hydroxy-2-nonenal; D001205:Ascorbic Acid; C024555:ferric chloride