Piroxicam and meloxicam ameliorate hepatic oxidative stress and protein carbonylation in Kupffer and sinusoidal endothelial cells promoted by ischemia-reperfusion injury.
The present study was aimed to assess the effect of protein carbonylation (PC) in hepatic cells and effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on indicators of tissue damage induced by liver ischemia-reperfusion injury (LIRI). Warm ischemia was performed by partial vascular occlusion during 90 min in Wistar rats. In serum, we determined the catalytic activity of Alanine Aminotransferase, Aspartate Aminotransferase, Lacticate Dehydrogenase, and Ornithine Carbamoyltransferase. In liver samples, we studied cellular alterations by means of histologic studies, lipid peroxidation, PC by immunohistochemistry, apoptosis and reactive oxygen species in bile by electron paramagnetic resonance. Based on PC data, sinusoidal endothelial cells (SEC) and Kupffer cells (KC) were the first to exhibit LIRI-associated oxidative damage and prior to parenchymal cells. Administration of piroxicam or meloxicam during the pre-ischemic period produced a highly significant decrease in all studied injury indicators. No significant differences were revealed between the protective action of the two drugs. The data shown here suggest the potential use of NSAIDs such as piroxicam or meloxicam in minimizing ischemic event-caused damage in liver. We also propose that PC may be employed as an adequate tool to assess tissue damage after oxidative stress.
Departamentos de Cirugía, Universidad Nacional Autónoma de México, Mexico City, Mexico.
Eduardo E
EE
Montalvo-Javé
José A
JA
Ortega-Salgado
Andrés
A
Castell
Daniel
D
Carrasco-Daza
David
D
Jay
Roberto
R
Gleason
Eduardo
E
Muñoz
César
C
Montalvo-Arenas
Rolando
R
Hernández-Muñoz
Enrique
E
Piña
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001219:Aspartate Aminotransferases / Q000378:metabolism; D002244:Carbon / Q000737:chemistry*; D042783:Endothelial Cells / Q000166:cytology*; D006801:Humans; D007728:Kupffer Cells / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D000077239:Meloxicam; D009954:Ornithine Carbamoyltransferase / Q000378:metabolism; D018384:Oxidative Stress; D010894:Piroxicam / Q000494:pharmacology*; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury; D013843:Thiazines / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011506:Proteins; D013843:Thiazines; D013844:Thiazoles; D010894:Piroxicam; D002244:Carbon; D007770:L-Lactate Dehydrogenase; D009954:Ornithine Carbamoyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000077239:Meloxicam