Review : All Obeticholic Acid Positive Aspects And Cons

7%) was similar to that developed at early reperfusion (IR5), Obeticholic Acid while increased damage was observed in IR60 hearts (49.2 �� 16.2%). Infarct size was significantly less in postconditioned heart groups (4.6 �� 1.6% in PC5 and 10.8 �� 1.2% in PC60), as well as in the PBN-treated group (7.1 �� 6.1%; Fig. 3). Oxidative modification of proteins by oxygen free radicals results in the introduction of carbonyl groups into protein side-chains. Carbonyl groups were derivatized to DNP-hydrazone and detected with primary antibodies specific to the DNP moiety of the proteins. Oxidative modification of proteins was initiated during ischaemia and increased dramatically in early reperfusion (IR5). With a longer reperfusion time (IR60), the response was slightly diminished, still higher than in ischaemia. Conversely, in the postconditioned hearts, carbonylation diminished after both 5 and 60 min of reperfusion; in the latter group, the oxidative damage to the proteins was almost undetectable (Fig. 4A). Lipid peroxidation was assessed by measuring levels of MDA. Maximal MDA production was detected at 5 min of reperfusion and remained high in the group subjected to 60 min reperfusion. The MDA content in postconditioned hearts was comparable to control levels (Fig. 4B). The content of CuZnSOD, MnSOD, catalase and GPx1 was compared in all groups (Fig. 5). A significant increase related to postconditioning was observed only for CuZnSOD content after prolonged reperfusion (Fig. 5A). Other enzymes, such as catalase (Fig. 5C) and Microbiology inhibitor GPx (Fig. 5D), were slightly augmented in PC60 hearts compared with IR60 hearts, but the differences were not statistically significant. We also evaluated the transcription levels of the four enzymes. We found a threefold increase in CuZnSOD transcription in PC60 hearts compared with IR60 hearts (P CDK9 homogenates. Upregulation was 47.3 �� 2.6 U (mg protein)?1) in PC60 versus 3.7 �� 2.8 U (mg protein)?1) in control hearts versus 30.0 �� 5.4 U (mg protein)?1) in IR60 hearts (Table 2). Using cytosolic and mitochondrial fractions to determine in-gel activities, we confirmed that ischaemia�Creperfusion increases the activity of both SOD isoforms; however, additional upregulation related to postconditioning was observed only in the activity of CuZnSOD (Fig. 7A). To determine whether upregulation of the level and activity of CuZnSOD may play a physiological role in protecting hearts against ischaemia�Creperfusion injury, we perfused DETC, a relatively specific inhibitor of both SODs, throughout the reperfusion protocol. There was a partial but significant decrease in cardiac double product after DETC administration compared with the postconditioned hearts (P