Back to Search
Start Over
Tibolone impairs glucose and fatty acid metabolism and induces oxidative stress in livers from female rats.
- Source :
-
European journal of pharmacology [Eur J Pharmacol] 2011 Oct 01; Vol. 668 (1-2), pp. 248-56. Date of Electronic Publication: 2011 Jul 08. - Publication Year :
- 2011
-
Abstract
- Tibolone is a synthetic steroid that has been extensively prescribed to treat climacteric symptoms and to prevent postmenopausal osteoporosis. Because menopause is a condition associated with increased incidence of metabolic disturbances and hepatic steatosis, the aim of this work was to evaluate the actions of tibolone on the liver. The effects of tibolone on glucose and fatty acid metabolism and on several parameters linked to mitochondrial energy metabolism, including the induction of cellular oxidative stress, were investigated in livers from female Wistar rats. Tibolone was assayed at concentrations ranging from 5 to 100 μM. In perfused livers, tibolone inhibited oxygen uptake, stimulated glycogenolysis and glycolysis, and inhibited gluconeogenesis from L-lactate and ketogenesis from exogenous octanotate. Tibolone also caused pronounced increases in both the cytosolic and mitochondrial NADH/NAD+ratios. In isolated mitochondria, tibolone inhibited oxygen uptake due to β-hydroxybutyrate and fatty acid oxidation without affecting the succinate oxidation. The inhibitory action of tibolone at complex I of the mitochondrial respiratory chain was suggested by the inhibition of the NADH-oxidase activity. Tibolone also induced oxidative stress in both perfused livers and isolated mitochondria, as indicated by the increased production of thiobarbituric acid reactive substances. These metabolic alterations may increase the risk of metabolic disturbances during tibolone administration, particularly in the postmenopausal condition.<br /> (Copyright © 2011 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Biological Transport drug effects
Carbon Dioxide metabolism
Catalase metabolism
Fasting
Female
Gluconeogenesis drug effects
Glutathione metabolism
Glycogen metabolism
Liver cytology
Liver enzymology
Mitochondria drug effects
Mitochondria metabolism
Oxygen metabolism
Perfusion
Rats
Rats, Wistar
Superoxide Dismutase metabolism
Thiobarbiturates metabolism
Fatty Acids metabolism
Glucose metabolism
Liver drug effects
Liver metabolism
Norpregnenes pharmacology
Oxidative Stress drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0712
- Volume :
- 668
- Issue :
- 1-2
- Database :
- MEDLINE
- Journal :
- European journal of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 21762690
- Full Text :
- https://doi.org/10.1016/j.ejphar.2011.06.043