[Effects of uncoupling proteins on nitric oxide synthesis and oxidative stress development in ishemia-reperfusion of old rat hearts].

Genipin is aglycone of geniposide, one of the active compounds of Gardenia gasminoides Ellis. The gardenia fruit extract has been used in traditional Chinese medicine to relieve the symptoms of type 2 diabetes that is accompanied with extensive oxidative stress and endothelial dysfunction of NO production. Besides, genipin was shown to inhibit UCP-depended proton leak through the inner mitochondrial membrane that leads to increased membrane potential and ATP production. We studied the effects of genipin at ischemia/reperfusion-induced oxidative stress and activity of NOS isozymes using Langendorfperfused old rat heart model. Ischemia/reperfusion is well-known oxidative agent, and showed significant increasing of superoxide radical, hydrogen peroxide and hydroxyl radical. Genipin application in doze 10-5 mol/L for 15 min before prolonged ischemia exerted powerful antiradical and antilipoperoxidative effects. Heart ischemia/reperfusion was supported with peroxynitrite generation and nitrozative stress. We demonstrated the inhibitory property of genipin on INOS expression that possibly occurs via protein kinase A inhibition and stabilization of I-kappaB-NF-kappaB complex. Genipin stimulated cNOS activity seemingly activating PI3K/Akt signaling pathway. Although, post-ischemic recovery ofcardiodynamic parameters of old rat hearts were depressed due to "switching off" the NO production by inducible NOS which is important in early period of reperfusion. Thus, we conclude that genipin is powerfull antioxidant and posses insulin-like activity due to its property of managing the NO production at intracellular signal transduction cascade level.