| The protection of brain mitochondria from oxidative stress is an important therapeutic strategy against ischemia-reperfusion injury and neurodegenerative disorders. Isolated brain mitochondria subjected to a 5 min period of anoxia followed by 5 min reoxygenation mirrored the effect of oxidative stress in the brain.(1). The present study attempts to evaluate the protective effects of endomorphin 1 (EM 1), endomorphin 2 (EM 2), and morphine (Mor) in an in vitro mouse brain mitochondria anoxia-reoxygenation model. Endomorphins (EM 1/2) and Mor were added to mitochondria prior to anoxia or reoxygenation. EM 1/2 and Mor markedly improved mitochondrial respiratory activity with a decrease in state 4 and increases in state 3, respiratory control ratio (RCR) and the oxidative phosphorylation efficiency (ADP/O ratio), suggesting that they may play a protective role in mitochondria. These drugs inhibited alterations in mitochondrial membrane fluidity, lipoperoxidation, and cardiolipin (CL) release, which indicates protection of the mitochondrial membranes from oxidative damage. The protective effects of these drugs were concentration-dependent. Furthermore, these drugs blocked the enhanced release of cytochrome c (Cyt c), and consequently inhibited the cell apoptosis induced by the release of Cyt c. Our results suggest that EM1/2 and Mor effectively protect brain mitochondria against oxidative stresses induced by in vitro anoxia-reoxygenation and may play an important role in the prevention of deleterious effects during brain ischemia-reperfusion and neurodegenerative diseases.(2). In the present study, an attempt has been made to evaluate the protective effects of caffeic acid phenethyl ester (CAPE) and its related phenolic compounds on mouse brain and liver mitochondria injury induced by in vitro anoxia-reoxygenation. Added before anoxia or reoxygenation, CAPE markedly protected coupled respiration with the decrease in state 4 and the increases in state 3, respiratory control ratio (RCR) and ADP/O ratio in a concentration-dependent manner. CAPE effectively protected mitochondria by inhibiting the mitochondrial membranes fluidity decrease, the lipoperoxidation and the protein carbonylation increase, which indicated its protective action against the mitochondrial oxidative damage. Meanwhile, CAPE blocked the enhanced release of cardiolipin (CL) and cytochrome c (Cyt c). The related phenolic compounds like caffeic acid (CA), ferulic acid (FA) and ethyl ferulate (EF) also had different-degree protective effects. CAPE and CAwere more potent than FA and EF. Their structural differences played the key role in their activity levels. These results suggest that CAPE and its related phenolic compounds protect mitochondria mainly correlated to their antioxidative activities and may be of interest for the prevention and therapy of ischemia-reperfusion injuries. |
