Effects of the nonsteroidal anti-inflammatory drug piroxicam on rat liver mitochondria.
1. The effects of piroxicam, a nonsteroidal anti-inflammatory drug, on rat liver mitochondria were investigated in order to obtain direct evidence about a possible uncoupling effect, as suggested by a previous work with the perfused rat liver. 2. Piroxicam increased respiration in the absence of exogenous ADP and decreased respiration in the presence of exogenous ADP, the ADP/O ratios and the respiratory control ratios. 3. The ATPase activity of intact mitochondria was increased by piroxicam. With 2,4-dinitrophenol uncoupled mitochondria, inhibition was observed. The ATPase activity of freeze-thawing disrupted mitochondria was insensitive to piroxicam. 4. Swelling driven by the oxidation of several substrates and safranine uptake induced by succinate oxidation were inhibited. 5. The results of this work represent a direct evidence that piroxicam acts as an uncoupler, thus, decreasing mitochondrial ATP generation.
Salgueiro-Pagadigorria
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CL
Department of Biochemistry, University of Maringá, Brazil.
Kelmer-Bracht
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AM
Bracht
A
A
Ishii-Iwamoto
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EL
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000633:toxicity*; D001665:Binding Sites; D004396:Coloring Agents / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008933:Mitochondrial Swelling / Q000187:drug effects; D009097:Multienzyme Complexes / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D009245:NADH Dehydrogenase / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D010619:Phenazines / Q000378:metabolism; D010894:Piroxicam / Q000008:administration & dosage / Q000633:toxicity*; D011048:Polarography; D051381:Rats; D017208:Rats, Wistar; D013056:Spectrophotometry, Ultraviolet; D014475:Uncoupling Agents / Q000633:toxicity*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004396:Coloring Agents; D008565:Membrane Proteins; D009097:Multienzyme Complexes; D010619:Phenazines; D014475:Uncoupling Agents; D009243:NAD; D010894:Piroxicam; D000244:Adenosine Diphosphate; D010088:Oxidoreductases; C022691:succinate oxidase; C023107:NADH oxidase; D009247:NADH, NADPH Oxidoreductases; D009245:NADH Dehydrogenase; D000251:Adenosine Triphosphatases; C009195:safranine T