Reducing the oxidative stress mediates the cardioprotection of bicyclol against ischemia-reperfusion injury in rats

Abstract

Abstract:Objective: To investigate the beneficial effect of bicyclol on rat hearts subjected to ischemia-reperfusion (IR) injuries and its possible mechanism. Methods: 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. Results: 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. Conclusions: Bicyclol exerts cardioprotection against IR injury, at least, via reducing oxidative stress and its subsequent mPTP opening.

Cardioprotective Effects of Luteolin on Ischemia/Reperfusion Injury in Diabetic Rats Are Modulated by eNOS and the Mitochondrial Permeability Transition Pathway

“…Using an established protocol, 28,33,34 single ventricular myocytes were prepared from adult rats by enzymatic dissociation. Briefly, the heart was perfused at 378C with 100% oxygenated, Ca 2+ -free Tyrode's solution, and then the solution was switched to 100% oxygenated, recirculating low-Ca 2+ Tyrode's containing 0.03% collagenase and 1% bovine serum albumin for 10 minutes.…”

Bicyclol in the treatment of patients with chronic diffuse liver diseases

“…Протективный эффект Бициклола был доказан в работах in vitro и in vivo, моделирующих различные формы повреждения печени четыреххлористым углеродом, ацетаминофеном, D-галактозамином и конкавалином А. Бициклол угнетает продукцию фактора некроза опухоли активными нейтрофилами, купферовскими клетками и макрофагами, а также способствует уменьшению интенсивности свободнорадикального повреждения (рис. 1) [8][9][10][11][12][13][14][15][16][17][18].…”

“…10,0 (7,(6)(7)(8)(9)(10)(11)(12)(13)0) 40-49 17,2 (11,(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)2) 36, 3 (26,9-49,1) 50-99 46, 8 (36,5-59,9) 89,4 (71,9-111,2) >100 61, 6 (38,9-97,6) 178, 8 (115,5-254,9) Уровень АЛТ в сыворотке крови (ед/л) (5,(8)(9)9) 40-49 21,4 (15,2) 17,8 (13,2) 50-99 27,5 (20,9) 31,6 (25,0-40,0) >100 30,0 (16,9) 82, 8 (58,4-117,5) Примечание. Скорректировано по возрасту, индексу массы тела, курению, потреблению алкоголя, уровню глюкозы в плазме, уровню общего холестерина в сыворотке крови, артериальному давлению и семейному анамнезу заболевания печени.…”

Remifentanil functions in the adaptive protection of cardiac function following ischemia

“…If mitochondria are protected, however, myocardial cell function can gradually recover to avoid causing irreversible damage (23). It has previously been suggested that mitochondrial calcium overload is an important contributory factor to myocardial injury during ischemia-reperfusion (24). Free and stable Ca 2+ regulation is necessary for ATP production in the mitochondria (25).…”