Elevated semicarbazide-sensitive amine oxidase (SSAO) activity in lung with ischemia-reperfusion injury: protective effect of ischemic preconditioning plus SSAO inhibition.
Ischemic preconditioning (IP) has been shown to protect the lung against ischemia-reperfusion (I/R) injury. Although the production of reactive oxygen species (ROS) has been postulated to play a crucial role in I/R injury, the sources of these radicals in I/R and the mechanisms of protection in IP remain unknown. Since it was postulated that deamination of endogenous and exogenous amines by semicarbazide-sensitive amine oxidase (SSAO) in tissue damage leads to the overproduction of hydrogen peroxide (H2O2), we investigated the possible contribution of tissue SSAO to excess ROS generation and lipid peroxidation during I/R and IP of the lung. Male Wistar rats were randomized into 6 groups: control lungs were subjected to 30 min of perfusion in absence and presence of SSAO inhibitor, whereas the lungs of the I/R group were subjected to 2 h of cold ischemia following the 30 min of perfusion in absence and presence of SSAO inhibitor. IP was performed by two cycles of 5 min ischemia followed by 5 min of reperfusion prior to 2 h of hypothermic ischemia in absence and presence of SSAO inhibitor. Lipid peroxidation, reduced (GSH) and oxidized (GSSG) glutathione levels, antioxidant enzyme activities, SSAO activity, and H2O2 release were determined in tissue samples of the study groups. Lipid peroxidation, glutathione disulfide (GSSG) content, SSAO activity and H2O2 release were increased in the I/R group, whereas GSH content, GSH/GSSG ratio and antioxidant enzyme activities were decreased. SSAO activity, H2O2 release, GSSG content and lipid peroxidation were markedly decreased in the IP group, whereas GSH content, GSH/GSSG ratio and antioxidant enzyme activities were significantly increased. SSAO activity was found to be positively correlated with H2O2 production in all study groups. Increased lipid peroxidation, SSAO activity, GSSG and H2O2 contents as well as decreased GSH and antioxidant enzyme levels in I/R returned to their basal levels when IP and SSAO inhibition were applied together. The present study suggests that application of IP and SSAO inhibition together may be more effective than IP alone against I/R injury in the lung.
Ucar
Gulberk
G
Department of Biochemistry, Faculty of Pharmacy, Hacettepe University, 06100, Ankara, Turkey. gulberk@hacettepe.edu.tr
Topaloglu
Eda
E
Burak Kandilci
H
H
Gumusel
Bulent
B
D006631:Amine Oxidase (Copper-Containing) / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D066298:In Vitro Techniques; D019194:Ischemic Preconditioning; D015227:Lipid Peroxidation; D008168:Lung / Q000201:enzymology* / Q000473:pathology; D008297:Male; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury; D013482:Superoxide Dismutase / Q000378:metabolism
D000975:Antioxidants; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D006631:Amine Oxidase (Copper-Containing); D005980:Glutathione Reductase; D005982:Glutathione Transferase; D005978:Glutathione; D019803:Glutathione Disulfide