Protective effects of ischemic preconditioning and application of lipoic acid prior to 90 min of hepatic ischemia in a rat model

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.

Pretreatment with adenosine and adenosine A1 receptor agonist protects against intestinal ischemia-reperfusion injury in rat

AIM： To examine the effects of adenosine and A1 receptor activation on reperfusion-induced small intestinal injury. METHODS： Rats were randomized into groups with sham operation, ischemia and reperfusion, and systemic treatments with either adenosine or 2-chloro-N^6-cyclopentyladenosine, A1 receptor agonist or 8-cyclopentyl- 1,3-clipropylxanthine, A1 receptor antagonist, plus adenosine before ischemia. Following reperfusion, contractions of ileum segments in response to KCl, carbachol and substance P were recorded. Tissue myeloperoxidase,malondialdehyde, and reduced glutathione levels were measured. RESULTS： Ischemia significantly decreased both contraction and reduced glutathione level which were ameliorated by adenosine and agonist administration. Treatment also decreased neutrophil infiltration and membrane lipid peroxidation. Beneficial effects of adenosine were abolished by pretreatment with A1 receptor antagonist. CONCLUSION： The data suggest that adenosine and A1 receptor stimulation attenuate ischemic intestinal injury via decreasing oxidative stress, lowering neutrophil infiltration, and increasing reduced glutathione content.