Ultrastructural effects of lipid peroxidation on the cardiac sarcolemma of the isolated rat heart

Author(s):  
T. Oguro ◽  
T. Onodera ◽  
M. Ashraf

Previously we reported that hydrogen peroxide (H2O2) is primarily cytotoxic to the cardiac cell membranes presumably through lipid peroxidation (LP). However, the effect of LP on the altered cell membrane permeability remains unknown. In this study, we evaluated the ultrastructural effects of LP on the sarcolemma of the isolated rat heart using H2O2 and N,N’-diphenyl-p-phenylene diamine (DPPD), an antilipid peroxidative agent.The hearts were perfused with 300 μM H2O2 for 15 minutes. In the other experiment the hearts were perfused with 2.5 μM DPPD for 20 minutes prior to perfusion with H2O2 for 15 minutes. Coronary effluent was collected at the end of the equilibration period and during H2O2 treatment for malondialdehyde (MDA) determination. Two minutes prior to the termination of the experiment, horseradish peroxidase (HRP: 220 U/mg × 55 mg) was perfused to assess the enhanced permeability of the cell membranes. The tissue slices were incubated in Graham-Karnovsky medium for one hour followed by postfixation with buffered 1% OsO4.

2020 ◽  
Author(s):  
Saman Atashbar ◽  
Elham Mohammad Khanlou ◽  
Saleh Khezri ◽  
Peyman Kurdpour ◽  
Ahmad Salimi

Abstract Background In spite of the cardiotoxic effect of selective cyclooxygenase-2 inhibitors, they are most widely used as anti-inflammatory and analgesic drugs. Today, valdecoxib and rofecoxib have been withdrawn on the market but celecoxib remains. In this study, we focused on an analysis of celecoxib toxic effects on isolated mitochondrial. Methods isolated rat heart mitochondria were obtained using differential centrifugation. Using flowcytometry and biochemical assays we searched succinate dehydrogenases (SDH), mitochondrial membrane potential (MMP), reactive oxygen species (ROS) formation, mitochondrial swelling, lipid peroxidation and mitochondrial complexes activity in rat heart isolated mitochondria. Results In here our results indicated a significant decrease in activity of complexes IV after exposure with celecoxib (16 µg/ml). This decrease in activity of complexes IV is paralleled by the MMP collapse, ROS formation, mitochondrial swelling and lipid peroxidation. Conclusion For the first time, this introductory study has showed a significant decrease in activity of complexes IV and mitochondrial dysfunction after exposure with celecoxib in rat heart isolated mitochondria.


Nature ◽  
1966 ◽  
Vol 211 (5049) ◽  
pp. 646-647 ◽  
Author(s):  
A. N. E. ZIMMERMAN ◽  
W. C. HÜLSMANN

1996 ◽  
Vol 84 (1) ◽  
pp. 117-127 ◽  
Author(s):  
Naohiro Kokita ◽  
Akiyoshi Hara

Background Oxygen-derived free radicals are involved in tissue damage during myocardial ischemia and reperfusion. Recent in vitro studies have demonstrated that a beneficial effect of propofol lies on its free radical scavenging properties. The current study, therefore, examined whether propofol is effective against the mechanical and metabolic damage induced by exogenously administered hydrogen peroxide in the isolated rat heart. Methods Rat hearts were perfused aerobically with Krebs-Henseleit bicarbonate buffer at a constant flow rate according to Langendorff's technique, while being paced electrically. Hearts were studied in control Krebs-Henseleit bicarbonate buffer, with Intralipid vehicle, with 25 microM or 50 microM propofol for 40 min, and with 50 microM propofol for 30 min followed by Intralipid for 10 min. A similar set of hearts was treated with hydrogen peroxide for 4 min, either in the absence of or beginning 10 min after Intralipid or propofol infusion. Left ventricular pressure was recorded as an index of mechanical function. The tissue concentrations of adenosine triphosphate, adenosine diphosphate, adenosine monophosphate, and creatine phosphate were measured as indices of energy metabolism. The tissue concentration of malondialdehyde was measured to evaluate lipid peroxidation. Results Hydrogen peroxide (600 microM) significantly increased the left ventricular end-diastolic pressure, decreased the left ventricular developed pressure (i.e., it produced mechanical dysfunction), and decreased tissue concentrations of adenosine triphosphate and creatine phosphate (i.e., metabolic damage). Hydrogen peroxide also increased the tissue concentration of malondialdehyde. These mechanical and metabolic alterations induced by hydrogen peroxide were significantly attenuated by propofol (25 microM or 50 microM), while the increase in malondialdehyde was completely suppressed by propofol. Conclusions The current study demonstrates that in the isolated heart, propofol attenuates both mechanical and metabolic changes induced by exogenously applied hydrogen peroxide. The beneficial action of propofol is probably correlated with reduction of the hydrogen peroxide-induced lipid peroxidation.


Author(s):  
Tetyana V Shimanskaya ◽  
Yulia V. Goshovska ◽  
Olena M. Semenykhina ◽  
Vadim F. Sagach

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