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The uncoupling effect of the nonsteroidal anti-inflammatory drug nimesulide in liver mitochondria from adjuvant-induced arthritic rats.
- Source :
-
Cell biochemistry and function [Cell Biochem Funct] 2001 Jun; Vol. 19 (2), pp. 117-24. - Publication Year :
- 2001
-
Abstract
- The aim of the present study was to evaluate the changes caused by adjuvant-induced arthritis in liver mitochondria and to investigate the effects of the nonsteroidal anti-inflammatory drug nimesulide. The main alterations observed in liver mitochondria from arthritic rats were: higher rates of state IV and state III respiration with beta-hydroxybutyrate as substrate; reduced respiratory control ratio and impaired capacity for swelling dependent on beta-hydroxybutyrate oxidation. No alterations were found in the activities of NADH oxidase and ATPase. Nimesulide produced: (1) stimulation of state IV respiration; (2) decrease in the ADP/O ratio and in the respiratory control ratio; (3) stimulation of ATPase activity of intact mitochondria; (4) inhibition of swelling driven by the oxidation of beta-hydroxybutyrate; (5) induction of passive swelling due to NH(3)/NH(4)+ redistribution. The activity of NADH oxidase was insensitive to nimesulide. Mitochondria from arthritic rats showed higher sensitivity to nimesulide regarding respiratory activity. The results of this work allow us to conclude that adjuvant-induced arthritis leads to quantitative changes in some mitochondrial functions and in the sensitivity to nimesulide. Direct evidence that nimesulide acts as an uncoupler was also presented. Since nimesulide was active in liver mitochondria at therapeutic levels, the impairment of energy metabolism could lead to disturbances in the liver responses to inflammation, a fact that should be considered in therapeutic intervention.<br /> (Copyright 2001 John Wiley & Sons, Ltd.)
- Subjects :
- Adenosine Triphosphatases drug effects
Adenosine Triphosphatases metabolism
Adenosine Triphosphate metabolism
Animals
Arthritis, Experimental chemically induced
In Vitro Techniques
Male
Membrane Proteins drug effects
Membrane Proteins metabolism
Mitochondria, Liver metabolism
Multienzyme Complexes drug effects
Multienzyme Complexes metabolism
NADH, NADPH Oxidoreductases drug effects
NADH, NADPH Oxidoreductases metabolism
Oxidative Phosphorylation drug effects
Oxygen Consumption drug effects
Polarography
Rats
Rats, Wistar
Uncoupling Agents metabolism
Anti-Inflammatory Agents, Non-Steroidal pharmacology
Arthritis, Experimental metabolism
Energy Metabolism drug effects
Mitochondria, Liver drug effects
Sulfonamides pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0263-6484
- Volume :
- 19
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Cell biochemistry and function
- Publication Type :
- Academic Journal
- Accession number :
- 11335936
- Full Text :
- https://doi.org/10.1002/cbf.904