COX-1 and COX-2 Inhibitors Ameriolates Hepatic Oxidative Stress During Ischemia Reperfusion Injury In Rat
Eduardo Montalvo-jave1, Arturo Ortega-Salgado2, Montalvo-Arenas Cesar1, Enrique Pina1, Carrasco Daniel2, David Jay3, Andres Castel1, Roberto Gleason4; 1Surgery, Cell Biology and Biochemistry, Faculty of Medicine , UNAM, Mexico City, Mexico; 2Department of Pediatric Surgery and Pathology. , National Institute of Pediatrics., Coyoacan, Mexico City , Mexico ; 3Cardiovascular Molecular Biomedicine. , National Institute of Cardiology, Tlalpan, Mexico City , Mexico ; 4Department of Solid State . , Institute of Physic , UNAM, Coyoacan, Mexico City , Mexico
Background and aims. The hepatic ischemia-reperfusion injury (HIRI). is associated with liver transplantation, hepatic surgical procedures or trauma and the oxidative damage induced after HIRI is considered to be the first event leading to graft dysfunction and to a rise in reactive oxygen species (ROS). The aims of the present study was to characterize some changes due to the increased presence of ROS, such as lipid peroxidation (LP), protein carbonylation (PC), and release of serum enzymes (SE) during HIRI. And evaluate the effect of the COX-1 (Piroxicam) and COX-2 (Meloxicam) inhibitors during the (HIRI) Methods. 90 male Wistar rats, allocated randomly to 9 study groups (n=10), were subjected to 30 m of total warm liver ischemia and the determinations were made at 0, 0.5, 1.0, 1.5, 2.0, 4.0, 12, and 24 h after reperfusion. The following indicators were quantified in liver biopsies: LP levels measured as thiobarbituric acid-reactive substances (TBARS), PC measured immunohistochemically (IHCh) by bound 2,4-dinitrophenylhydrazine to proteins, and SE activities of LDH, AST, ALT, and OTC released from the liver. The ROS activity was evaluate in bile samples using electron paramagnetic resonance (EPR) Results. Increased TBARS levels and PC were found at 1.0, 1.5, and 2.0 h. Serum levels of OTC, AST, ALT, and LDH were increased during the reperfusion phase, especially during the period between 1.0 and 4.0 h. In the group of COX-1 and 2 the TBARS, SE, PC and EPR activity was ameliorates compared with sham group. Conclusions. The protective effects of the COX-1 and 2 was investigated in the prevention of free radical mediated tissue damage in liver ischemia-reperfusion injury. The temporal course of the oxidative stress and its correlation with SE in 24 hours after our experiments suggest that generation of ROS during total HIRI are responsible, at least partially for the transient rise in TBARS, PC and catalytic activity of serum enzymes with a maximum effects at around 2 h after reperfusion.
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