bicyclol and Reperfusion-Injury

To investigate the beneficial effect of bicyclol on rat hearts subjected to ischemia-reperfusion (IR) injuries and its possible mechanism.. Male Sprague-Dawley rats were intragastrically administered with bicyclol (25, 50 or 100 mg/(kg∙d)) for 3 d. Myocardial IR was produced by occlusion of the coronary artery for 1 h and reperfusion for 3 h. Left ventricular hemodynamics was continuously monitored. At the end of reperfusion, myocardial infarct was measured by 2,3,5-triphenyltetrazolium chloride (TTC) staining, and serum lactate dehydrogenase (LDH) level and myocardial superoxide dismutase (SOD) activity were determined by spectrophotometry. Isolated ventricular myocytes from adult rats were exposed to 60 min anoxia and 30 min reoxygenation to simulate IR injuries. After reperfusion, cell viability was determined with trypan blue; reactive oxygen species (ROS) and mitochondrial membrane potential of the cardiomyocytes were measured with the fluorescent probe. The mitochondrial permeability transition pore (mPTP) opening induced by Ca(2+) (200 μmol/L) was measured with the absorbance at 520 nm in the isolated myocardial mitochondria.. Low dose of bicyclol (25 mg/(kg∙d)) had no significant improving effect on all cardiac parameters, whereas pretreatment with high bicyclol markedly reduced the myocardial infarct and improved the left ventricular contractility in the myocardium exposed to IR (P<0.05). Medium dose of bicyclol (50 mg/(kg∙d)) markedly improved the myocardial contractility, left ventricular myocyte viability, and SOD activity, as well decreased infarct size, serum LDH level, ROS production, and mitochondrial membrane potential in rat myocardium exposed to IR. The reduction of ventricular myocyte viability in IR group was inhibited by pretreatment with 50 and 100 mg/(kg∙d) bicyclol (P<0.05 vs. IR), but not by 25 mg/(kg∙d) bicyclol. The opening of mPTP evoked by Ca(2+) was significantly inhibited by medium bicyclol.. Bicyclol exerts cardioprotection against IR injury, at least, via reducing oxidative stress and its subsequent mPTP opening.

Topics: Animals; Biphenyl Compounds; Cardiotonic Agents; Cells, Cultured; Male; Mitochondrial Membrane Transport Proteins; Mitochondrial Permeability Transition Pore; Oxidative Stress; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Reperfusion Injury; Treatment Outcome

To assess its potential neuroprotective effect against ischemia/reperfusion (IR) injury in mice, bicyclol was administered intragastrically once a day for 3 days. After 6h of bicyclol pretreatment on the third day, forebrain ischemia was induced for 1h by bilateral occlusion of the carotid arteries. After different times of reperfusion, the histopathological changes and the levels of mitochondria-generated reactive oxygen species (ROS), malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) in the cortex and hippocampus were measured. We found that extensive neuronal death occurred in the cortex and the CA1 area of the hippocampus at day 7 after IR and that bicyclol significantly attenuated IR-induced neuronal death in a dose-dependent manner. We also found that pretreatment with bicyclol dose dependently decreased the generation of ROS and the MDA content and reduced the compensatory increase in SOD activity in the cortex and hippocampus at 4h of reperfusion. These results suggest that bicyclol protects the mouse brain against cerebral IR injury by attenuating oxidative stress and lipid peroxidation.

Topics: Animals; Biphenyl Compounds; Brain Ischemia; Cell Count; Cell Death; Cell Survival; Cerebral Cortex; Dose-Response Relationship, Drug; Hippocampus; Male; Malondialdehyde; Mice; Mice, Inbred ICR; Mitochondria; Neurons; Neuroprotective Agents; Oxidative Stress; Reactive Oxygen Species; Reperfusion Injury; Superoxide Dismutase

To investigate the protective effect of bicyclol on kidney injury induced by ischemia-reperfusion in rats.. Bicyclol was orally administered to rats at doses of 50 and 200 mg.kg-1 before ischemia-reperfusion injury to evaluate the influence of bicyclol on the formation of MDA and BUN in serum, the content of GSH and the activity of GST in kidney, as well as kidney mitochondria membrane fluidity in ischaemia-reperfusion rats.. Bicyclol given orally at doses of 50 and 200 mg.kg-1 was shown to significantly decrease the increment of MDA and BUN in serum and protect the GSH depletion in kidney. Bicyclol was also shown to induce kidney GST and ameliorate the decrease of mitochondria membrane fluidity. The protective effects of bicyclol on kidney injury induced by ischemia-reperfusion are dose-dependent.. The protective action of bicyclol on kidney injury induced by ischemia-reperfusion may be attributed to its induction of kidney GSH and the GST, stabilization on mitochondria membrane and the inhibition on lipid peroxidation.

Topics: Animals; Biphenyl Compounds; Blood Urea Nitrogen; Disease Models, Animal; Glutathione; Glutathione Transferase; Ischemia; Kidney Diseases; Male; Malondialdehyde; Membrane Fluidity; Mitochondria; Protective Agents; Rats; Reperfusion Injury