plastochromanol-8 and Reperfusion-Injury

Ischemia-induced mitochondrial dysfunction and ATP depletion in the kidney result in disruption of primary functions and acute injury of the kidney. This study tested whether γ-tocotrienol (GTT), a member of the vitamin E family, protects mitochondrial function, reduces ATP deficits, and improves renal functions and survival after ischemia/reperfusion injury. Vehicle or GTT (200 mg/kg) were administered to mice 12 h before bilateral kidney ischemia, and endpoints were assessed at different timepoints of reperfusion. GTT treatment reduced decreases in state 3 respiration and accelerated recovery of this function after ischemia. GTT prevented decreases in activities of complexes I and III of the respiratory chain, and blocked ischemia-induced decreases in F

Topics: Acute Kidney Injury; Adenosine Triphosphate; Animals; Chromans; Electron Transport; Energy Metabolism; Male; Mice; Mice, Inbred C57BL; Mitochondria; Protective Agents; Reperfusion Injury; Vitamin E

This study compared two dietary phytochemicals, grape-derived resveratrol and palm oil-derived γ-tocotrienol, either alone or in combination, on the contribution of autophagy in cardioprotection during ischaemia and reperfusion. Sprague-Dawley rats weighing between 250 and 300 g were randomly assigned to one of the following groups: vehicle, ischaemia/reperfusion (I/R), resveratrol + I/R, γ-tocotrienol + I/R, resveratrol +γ-tocotrienol + I/R. For resveratrol treatments, the rats were gavaged with resveratrol (2.5 mg/kg) for 15 days while for γ-tocotrienol experiments the rats were gavaged with γ-tocotrienol (0.3 mg/kg) for 30 days. For the combined resveratrol +γ-tocotrienol experiments, the rats were gavaged with γ-tocotrienol for 15 days, and then gavaging continued with resveratrol along with γ-tocotrienol for a further period of 15 days. After 30 days, isolated perfused hearts were subjected to 30 min. of global ischaemia followed by 2 hrs of reperfusion. Our results showed for the first time that at least in part, the cardioprotection (evidenced from the ventricular performance, myocardial infarct size and cardiomyocyte apoptosis) with resveratrol and γ-toctrienol was achieved by their abilities to induce autophagy. Most importantly, resveratrol and γ-tocotrienol acted synergistically providing greater degree of cardioprotection simultaneously generating greater amount of survival signal through the activation of Akt-Bcl-2 survival pathway. Autophagy was accompanied by the activation of Beclin and LC3-II as well as mTOR signalling, which were inhibited by either 3-methyl adenine (3-MA) or Wortmannin. The autophagy was confirmed from the results of transmission electron microscopy and light microscopy as well as with confocal microscopy. It is tempting to speculate that during ischaemia and reperfusion autophagy along with enhanced survival signals helps to recover the cells from injury.

Topics: Animals; Antioxidants; Apoptosis; Autophagy; Cardiotonic Agents; Chromans; Drug Synergism; Male; Myocardial Infarction; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Resveratrol; Signal Transduction; Stilbenes; Vitamin E