Neuroprotective and cardioprotective actions of an association of pyruvate, vitamin E and fatty acids.
Oxidative stress may involve overproduction of hydrogen peroxide which can generate highly cytotoxic hydroxyl radicals in the presence of ferrous ions. This work demonstrates that TCAT (Tricomponent Antioxidant Therapy), an association of pyruvate, vitamin E and fatty acids, provides neuronal and cardiac protection in oxidative stress, ex vivo. Mouse P19 neuron cultures were exposed for 30 min to low millimolar H2O2 concentrations in the absence or presence of Fe2+. Concentrations 1X (10 mmol/L pyruvate, 0.1 U/mL vitamin E and 0.1% fatty acids) and 3X of TCAT, respectively, prevented neuronal death caused by these treatments. Analysis of the contribution of TCAT components to neuroprotection showed that vitamin E and fatty acids enhanced pyruvate action whereas they displayed no neuroprotection by themselves. In contrast, vitamin E and fatty acids were as potent antioxidants as pyruvate in an in vitro cell-free assay, indicating that TCAT protection is modulated by the existence of the cellular membrane barriers. Isolated rat hearts were perfused under electrolysis or subjected to regional ischemia-reperfusion. TCAT 1X prevented the electrolysis-induced decrease in left ventricular pressure, heart rate and coronary flow. At 0.25X concentration, TCAT abolished the incidence of irreversible ventricular fibrillation in ischemia-reperfusion. The results indicate that TCAT could have a broad therapeutic utility in neurological and cardiac injuries associated with oxidative stress. The protective action of TCAT can surpass that of its components, revealing a benefit of the association.
Paquin
Joanne
J
Département de chimie et de biochimie, Université du Québec à Montréal, Montreal, Québec, Canada.
Aouffen
M'hammed
M
De Grandpré
Eric
E
Nadeau
Réginald
R
Langlois
Denis
D
Mateescu
Mircea-Alexandru
MA
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002474:Cell-Free System; D004338:Drug Combinations; D005227:Fatty Acids / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000633:toxicity; D066298:In Vitro Techniques; D007501:Iron / Q000633:toxicity; D008297:Male; D051379:Mice; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016877:Oxidants / Q000633:toxicity; D010655:Phenylenediamines / Q000494:pharmacology; D019289:Pyruvic Acid / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014810:Vitamin E / Q000494:pharmacology*
D000975:Antioxidants; D002316:Cardiotonic Agents; D004338:Drug Combinations; D005227:Fatty Acids; D018696:Neuroprotective Agents; D016877:Oxidants; D010655:Phenylenediamines; D014810:Vitamin E; D019289:Pyruvic Acid; C013935:N,N-diethyl 4-phenylenediamine; D006861:Hydrogen Peroxide; D007501:Iron