lithium-chloride and indirubin-3--monoxime

The aim of this study was to examine the effects of GSK-3 β inhibitors compared with PRE and POS in spontaneously hypertensive rats (SHR). Isolated hearts were submitted to the following protocols: IC: 45 min global ischemia (GI) and 1-hour reperfusion (R); PRE: a cycle of 5 min GI and 10 minutes of R prior to 45 min GI; POS: three cycles of 30 sec GI/30 sec R at the start of R. Other hearts received lithium chloride (LiCl) or indirubin-3'-monoxime,5-iodo-(IMI) as GSK-3 β inhibitors. All interventions reduced the infarct size observed in IC group. The expressions of P-GSK-3 β and P-Akt decreased in IC and were restored after PRE, POS, and GSK-3 β inhibitors treatments. An increase of cytosolic MnSOD activity and lipid peroxidation and a decrease of GSH content observed in IC hearts were attenuated in PRE, POS, and LiCl or IMI treatments. An increase of P-GSK-3 β /VDAC physical association and a partial recovery of mitochondrial permeability were also detected after interventions. These data show that, in SHR hearts, GSK-3 β inhibitors mimic the cardioprotection afforded by PRE and POS and suggest that a decrease in mitochondrial permeability mediated by P-GSK-3 β /VDAC interaction is a crucial event.

Topics: Animals; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Heart; Humans; Hypertension; Indoles; Ischemic Postconditioning; Ischemic Preconditioning; Lipid Peroxidation; Lithium Chloride; Organ Culture Techniques; Oximes; Phosphorylation; Proto-Oncogene Proteins c-akt; Rats; Reperfusion Injury