Cardioprotective effects of dihydrolipoic acid and tocopherol in right heart hypertrophy during oxidative stress.
Rat hearts hypertrophied by exposure of the animals to low oxygen pressure were perfused by the Langendorff technique. After oxidative stress induced by hypoxia/reoxygenation, functional recovery of the hypertrophied right heart was insufficient when compared to non-hypertrophied controls. Accordingly, mitochondrial membrane potential did not recover sufficiently. There was a positive trend for improvement of the rate-pressure product during reoxygenation in lipoic acid (CAS 1077-28-7; 0.8 mumol/l) treated hearts which was also verified for membrane potential. Adenosine 5'-triphosphate and creatine phosphate contents as well as the ATP/ADP ratio in hypertrophied right ventricle were significantly increased after reoxygenation in hearts treated with lipoic acid. With lipoic acid, there was a significantly higher content of glutathione (oxidized form) after reoxygenation, Ca2+ uptake was significantly increased in mitochondria isolated from hypertrophied right ventricles and treated by 12 nmol/mg protein of lipoic acid. The results reveal a distinct improvement of mitochondrial structure/function by lipoic acid and suggest for therapy a combination with the synergistic free radical scavenging properties of tocopherol (CAS 10191-41-0).
Thürich
T
T
Gustav-Embden-Zentrum der Biologischen Chemie, Arbeitsgruppe Membranstruktur.
Bereiter-Hahn
J
J
Schneider
M
M
Zimmer
G
G
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D002118:Calcium / Q000378:metabolism; D006332:Cardiomegaly / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D003326:Coronary Circulation / Q000502:physiology; D003402:Creatine Kinase / Q000378:metabolism; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D005978:Glutathione / Q000378:metabolism; D006334:Heart Function Tests; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008929:Mitochondria, Heart / Q000378:metabolism; D008933:Mitochondrial Swelling / Q000187:drug effects; D018384:Oxidative Stress / Q000502:physiology*; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D008063:Thioctic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014810:Vitamin E / Q000627:therapeutic use*
D000975:Antioxidants; D016166:Free Radical Scavengers; D014810:Vitamin E; D008063:Thioctic Acid; C015144:dihydrolipoic acid; D000255:Adenosine Triphosphate; D003402:Creatine Kinase; D005978:Glutathione; D002118:Calcium