Browsing by Author "Carreira, R"
Now showing 1 - 2 of 2
Results Per Page
Sort Options
- O Nicorandil preserva a funcionalidade do sistema fosforilativo e oxidativo mitocondrial num modelo animal de isquémia-reperfusão globalPublication . Carreira, R; Monteiro, P; Gonçalves, L; Providência, LAIschemia followed by reperfusion (IR) negatively affects mitochondrial function. At the level of the oxidative-phosphorylative system, IR inhibits the respiratory complexes and ATP synthase, and increases the passive leak of protons through the inner mitochondrial membrane, uncoupling respiration from phosphorylation, decreasing mitochondrial potential and, consequently, ATP production. Drugs that minimize the mitochondrial damage induced by IR may prove to be clinically effective. In the present work, we analyzed the impact of nicorandil, a mitochondrial ATP-sensitive potassium channel agonist, on mitochondrial dysfunction at the level of the oxidative-phosphorylative system of rat hearts subjected to IR. The decrease in the respiratory control ratio (RCR) induced by IR leads to the conclusion that IR has a negative impact on the activity of the mitochondrial respiratory system, uncoupling oxidation from phosphorylation. This effect is reversed by nicorandil, which increases not only RCR, but also the ADP/O ratio. Regarding respiratory rate, state 3 rate was approximately the same for all the experimental groups, while state 4 rate was lower for the group where IR was induced in the presence of nicorandil. This result is in accordance with the data obtained for the RCR and ADP/O. State 4 rate is most affected by uncoupling, given that it is controlled by proton leak. Mitochondria subjected to IR in the presence of nicorandil have a lower state 4 rate, i.e. they are less uncoupled. From these results we conclude that nicorandil preserves the function of mitochondria subjected to IR in terms of both respiration and phosphorylative capacity.
- O Carvedilol Protege Mitocôndrias Cardíacas Isquémicas de Lesões Induzidas Por Stress OxidativoPublication . Carreira, R; Duarte, AI; Monteiro, P; Santos, MS; Rego, AC; Oliveira, CR; Gonçalves, L; Providência, LAIschemia negatively affects mitochondrial function by inducing the mitochondrial permeability transition (MPT). The MPT is triggered by oxidative stress, which occurs in mitochondria during ischemia as a result of diminished antioxidant defenses and increased reactive oxygen species production. It causes mitochondrial dysfunction and can ultimately lead to cell death. Therefore, drugs able to minimize mitochondrial damage induced by ischemia may prove to be clinically effective. We analyzed the effect of carvedilol, a beta-blocker with antioxidant properties, on mitochondrial dysfunction. Carvedilol decreased levels of TBARS (thiobarbituric acid reactive substances), an indicator of oxidative stress, which is consistent with its antioxidant properties. Regarding cell death by apoptosis, although ischemia did increase caspase-8-like activity, there were no changes in caspase-3-like activity, which is activated downstream of caspase-8; this may indicate that the apoptotic cascade is not activated by 60 minutes of ischemia. We conclude that carvedilol protects ischemic mitochondria by preventing oxidative mitochondrial damage, and, by so doing, it may also inhibit the formation of the MPT pore.