TY - JOUR
T1 - Melatonin protects against taurolithocholic-induced oxidative stress in rat liver
AU - Fuentes-Broto, Lorena
AU - Miana-Mena, Francisco J.
AU - Piedrafita, Eduardo
AU - Berzosa, César
AU - Martínez-Ballarín, Enrique
AU - García-Gil, Francisco A.
AU - Reiter, Russel J.
AU - García, Joaquín J.
PY - 2010/8/1
Y1 - 2010/8/1
N2 - 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 FeCl3 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.
AB - 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 FeCl3 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.
KW - Bile acid
KW - Cholestasis
KW - Lipid peroxidation
KW - Melatonin
KW - Oxidative stress
KW - Protein carbonyls
KW - Taurolithocholic acid
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U2 - 10.1002/jcb.22636
DO - 10.1002/jcb.22636
M3 - Article
C2 - 20564217
AN - SCOPUS:77954918018
SN - 0730-2312
VL - 110
SP - 1219
EP - 1225
JO - Journal of Cellular Biochemistry
JF - Journal of Cellular Biochemistry
IS - 5
ER -