Inhibition of Glutathione S-Transferase by Ethacrynic Acid Augments Ischemia-Reperfusion Damage and Apoptosis and Attenuates the Positive Effect of Ischemic Postconditioning in a Bilateral Acute Hindlimb Ischemia Rat Model.

AIMS: We studied the effects of the inhibition of the endogene antioxidant glutathione-S-transferase (GST) by ethacrynic acid (EA) on ischemia-reperfusion (IR) injury and postconditioning (PC) in the lower extremities. We aimed to examine the oxidative stress parameters (OSP), inflammatory response and activation of proapoptotic signaling proteins (PSP) after revascularization surgery. METHODS: Sixty Wistar rats were divided into 6 groups: control, IR, PC, EA-control, IR and administration of EA (IR/EA) and PC and administration of EA (PC/EA). The IR, PC, IR/EA and PC/EA groups underwent 60 min of infrarenal aortic cross-clamping. After that, PC was performed in the PC and PC/EA groups. In 3 of the groups, the animals were treated with EA (EA-control, IR/EA and PC/EA groups) as well. The ischemia was followed by 120 min of reperfusion. Blood samples and biopsy specimens were collected from the quadriceps muscle. Plasma malondialdehyde, reduced glutathione, thiol/sulfhydryl group levels, TNF-α and IL-6 concentrations and superoxide-dismutase enzyme activity were measured. RESULTS: The levels of the OSP and the inflammatory proteins were higher in the EA-administered groups. The ratio of phosphorylated PSP was higher in the EA-administered groups and the protective effect of PC did not develop. CONCLUSIONS: Inhibition of GST by EA augmented the IR damage. GST inhibition was associated with a different activation of the mitogen-activated protein kinases and the PSP, regulating these pathways in the process of apoptosis and PC.

Pneumoperitoneum induced ischemia-reperfusion injury of the peritoneum - Preconditioning may reduce the negative side-effects caused by carbon-dioxide pneumoperitoneum - Pilot study.

INTRODUCTION: Laparoscopy is more beneficial than the conventional open technique, however the pneumoperitoneum created may have an ischemic side effect. OBJECTIVE: Our aim was to evaluate the protective effects of preconditioning during laparoscopic cholecystectomies (LC). METHODS: 30 patients were randomized into 2 groups: I. PreC (preconditioning: 5 min. inflation, 5 min. deflation, followed by conventional LC), II: LC (conventional LC). Blood samples were taken before hospitalization (C = control), before surgery, after anaesthesia (B.S.), after surgery (A.S.) and 24 hours after the procedure (24 h). Measured parameters were: malondialdehyde (MDA), reduced glutathione (GSH), sulfhydril groups (-SH), superoxide-dismutase (SOD), catalase (CAT), myeloperoxidase (MPO), length of hospitalization and pain (VAS = visual analogue scale). RESULTS: Compared to the BS levels, no significant changes were detected in SOD's activity and MDA levels. GSH concentrations were significantly increased in the PreC group after operation. SH-, MPO, CAT and liver function enzymes were not significantly different. Hospitalization was shorter in the PreC group. Based on the VAS score patients had less pain in the PreC group. CONCLUSION: Significant differences concerning PreC group were found in GSH values. In the PreC group pain decreased by 2-2.5 units following the procedure, 24 h after surgery, and hospitalisation was also significantly shorter. In our pilot study the potential protective effect of preconditioning could be defined.