Effects of the nonsteroidal anti-inflammatory drug nimesulide on energy metabolism in livers from adjuvant-induced arthritic rats.
The effects of nimesulide on energy metabolism and the hepatic metabolic alterations produced by adjuvant-induced arthritis were investigated in the perfused rat liver an in isolated liver mitochondria. Nimesulide, at therapeutic levels (20-50 microM), produced: (1) stimulation of oxygen consumption in the perfused rat liver and in isolated mitochondria, (2) inhibition of gluconeogenesis; (3) reduction of ADP/O ratio and the respiratory control ratio and stimulation of glycogenolysis in the livers from healthy rats, but not in livers from arthritic rats. These results indicate that nimesulide acts as a mitochondrial uncoupler. The main alterations produced by adjuvant-induced arthritis were: higher rates of oxygen consumption in both perfused livers and isolated mitochondria, with no decrease in the efficiency of mitochondrial energy transduction; (2) decreased gluconeogenesis and lack of glycogenolytic response to uncouplers, but not to alpha 1-agonists. These data allow to conclude that nimesulide-induced impairment of energy metabolism should worsen the hepatic disturbances that are already associated with the adjuvant disease.
Caparroz-Assef
S M
SM
Laboratory of Liver Metabolism and Biological Oxidations, University of Maringá, Brazil.
Bersani-Amado
C A
CA
do Nascimento
E A
EA
Kelmer-Bracht
A M
AM
Ishii-Iwamoto
E L
EL
D019297:2,4-Dinitrophenol / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000378:metabolism; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects*; D005215:Fasting; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008112:Liver Glycogen / Q000378:metabolism; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000494:pharmacology*; D014475:Uncoupling Agents / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000894:Anti-Inflammatory Agents, Non-Steroidal; D008112:Liver Glycogen; D013449:Sulfonamides; D014475:Uncoupling Agents; D000244:Adenosine Diphosphate; D019297:2,4-Dinitrophenol; D002118:Calcium; C012655:nimesulide; D009638:Norepinephrine