AIM： To compare different preconditioning strategies to protect the liver from ischemia/reperfusion injury focusing on the expression of pro- and anti-apoptotic proteins. Interventions comprised different modes of is...AIM： To compare different preconditioning strategies to protect the liver from ischemia/reperfusion injury focusing on the expression of pro- and anti-apoptotic proteins. Interventions comprised different modes of ischemic preconditioning （IP） as well as pharmacologic pretreatment by α-lipoic acid （LA）. METHODS： Several groups of rats were compared： sham operated animals, non-pretreated animals （nt）, animals receiving IP （10 rain of ischemia by clamping of the portal triad and 10 min of reperfusion） prior to sustained ischemia, animals receiving selective ischemic preconditioning （IPsel, 10 min of ischemia by selective clamping of the ischemic lobe and 10 rain of reperfusion） prior to sustained ichemia, and animals receiving 500 1μmol α-LA injected i.v. 15 min prior to the induction of 90 min of selective ischemia. RESULTS： Cellular damage was decreased only in the LA group. TUNEL-positive hepatocytes as well as necrotic hepatocyte injury were also decreased only by LA（19 ± 2 vs 10 ± 1, P〈 0.05 and 29 ± 5 vs 12 ± 1, P 〈 0.05）. Whereas caspase 3- activities in liver tissue were unchanged, caspase 9- activity in liver tissue was decreased only by LA pretreatment （3.1 ± 0.3 vs 1.8 ± 0.2, P 〈 0.05）. Survival rate as the endpoint of liver function was increased after IP and LA pretreatment but not after IPsel. Levels of lipid peroxidation （LPO） in liver tissue were decreased in the IP as well as in the LA group compared to the nt group. Determination of pro- and anti-apoptotic proteins showed a shift towards anti-apoptotic proteins by LA. In contrast, both our IP strategies failed to influence apototic cell death. CONCLUSION： IP, consisting of 10 min of ischemia and 10 min of reperfusion, ischemia/reperfusion injury protects only partly against of the liver prior to 90 min of selective ischemia. IPsel did not influence ischemic tolerance of the liver. LA improved tolerance to ischemia, possibly by downregulation of pro-apoptotic Bax.展开更多
AIM： To evaluate the protective effects of preconditioning by α-lipoic acid （LA） in patients undergoing hepatic resection under inflow occlusion of the liver. METHODS： Twenty-four patients undergoing liver resect...AIM： To evaluate the protective effects of preconditioning by α-lipoic acid （LA） in patients undergoing hepatic resection under inflow occlusion of the liver. METHODS： Twenty-four patients undergoing liver resection for various reasons either received 600 mg LA or NaCI 15 min before transection performed under inflow occlusion of the liver. Blood samples and liver wedge biopsy samples were obtained after opening of the abdomen immediately after inflow occlusion of the liver, and 30 min after the end of inflow occlusion of the liver. RESULTS： Serum levels of aspartate transferase and alanine transferase were reduced at all time points in patients who received LA in comparison to those who received NaCL. This was accompanied by reduced histomorphological features of oncosis. We observed TUNEL-positive hepatocytes in the livers of the untreated patients, especially after 30 min of ischemia. LA attenuated this increase of TUNEL-positive hepatocytes. Under preconditioning with LA, ATP content was significantly enhanced after 30 min of ischemia and after 30 min of reperfusion. CONCLUSION： This is the first report on the potential for LA reducing ischemia/reperfusion injury （IRI） of the liver in humans who were undergoing liver surgery. Beside its simple and rapid application, side effects did not occur. LA might therefore represent a new strategy against hepatic IRI in humans.展开更多
文摘AIM： To compare different preconditioning strategies to protect the liver from ischemia/reperfusion injury focusing on the expression of pro- and anti-apoptotic proteins. Interventions comprised different modes of ischemic preconditioning （IP） as well as pharmacologic pretreatment by α-lipoic acid （LA）. METHODS： Several groups of rats were compared： sham operated animals, non-pretreated animals （nt）, animals receiving IP （10 rain of ischemia by clamping of the portal triad and 10 min of reperfusion） prior to sustained ischemia, animals receiving selective ischemic preconditioning （IPsel, 10 min of ischemia by selective clamping of the ischemic lobe and 10 rain of reperfusion） prior to sustained ichemia, and animals receiving 500 1μmol α-LA injected i.v. 15 min prior to the induction of 90 min of selective ischemia. RESULTS： Cellular damage was decreased only in the LA group. TUNEL-positive hepatocytes as well as necrotic hepatocyte injury were also decreased only by LA（19 ± 2 vs 10 ± 1, P〈 0.05 and 29 ± 5 vs 12 ± 1, P 〈 0.05）. Whereas caspase 3- activities in liver tissue were unchanged, caspase 9- activity in liver tissue was decreased only by LA pretreatment （3.1 ± 0.3 vs 1.8 ± 0.2, P 〈 0.05）. Survival rate as the endpoint of liver function was increased after IP and LA pretreatment but not after IPsel. Levels of lipid peroxidation （LPO） in liver tissue were decreased in the IP as well as in the LA group compared to the nt group. Determination of pro- and anti-apoptotic proteins showed a shift towards anti-apoptotic proteins by LA. In contrast, both our IP strategies failed to influence apototic cell death. CONCLUSION： IP, consisting of 10 min of ischemia and 10 min of reperfusion, ischemia/reperfusion injury protects only partly against of the liver prior to 90 min of selective ischemia. IPsel did not influence ischemic tolerance of the liver. LA improved tolerance to ischemia, possibly by downregulation of pro-apoptotic Bax.
文摘AIM： To evaluate the protective effects of preconditioning by α-lipoic acid （LA） in patients undergoing hepatic resection under inflow occlusion of the liver. METHODS： Twenty-four patients undergoing liver resection for various reasons either received 600 mg LA or NaCI 15 min before transection performed under inflow occlusion of the liver. Blood samples and liver wedge biopsy samples were obtained after opening of the abdomen immediately after inflow occlusion of the liver, and 30 min after the end of inflow occlusion of the liver. RESULTS： Serum levels of aspartate transferase and alanine transferase were reduced at all time points in patients who received LA in comparison to those who received NaCL. This was accompanied by reduced histomorphological features of oncosis. We observed TUNEL-positive hepatocytes in the livers of the untreated patients, especially after 30 min of ischemia. LA attenuated this increase of TUNEL-positive hepatocytes. Under preconditioning with LA, ATP content was significantly enhanced after 30 min of ischemia and after 30 min of reperfusion. CONCLUSION： This is the first report on the potential for LA reducing ischemia/reperfusion injury （IRI） of the liver in humans who were undergoing liver surgery. Beside its simple and rapid application, side effects did not occur. LA might therefore represent a new strategy against hepatic IRI in humans.
