LE STRESS OXYDANT INDUIT PAR VOIE METABOLIQUE (REGIMES ALIMENTAIRES) OU PAR VOIE GAZEUSE (HYPEROXIE) ET EFFET DE LA GLISODIN®

MITOCHONDRIA, THROUGH ITS RESPIRATORY CHAIN, IS THE MAIN SOURCE OF REACTIVE OXYGEN SPECIES (ROS). TWO ESSENTIAL PARAMETERS CAN MODULATE THAT PRODUCTION: THE NATURE OF REDUCED EQUIVALENTS (NADH, H+ AND FADH2) AND THE SUPPLY IN OXYGEN. IN THE PRESENT STUDY, WE EXAMINED THE EFFECTS OF DIETS (MODIFYING THE PROPORTION BETWEEN NADH,H+ AND FADH2) AND OF HYPEROXIA (MODIFYING THE SUPPLY IN O2) ON THE PRODUCTION OF H2O2 BY SKELETAL MUSCLE AND/OR LIVER RAT MITOCHONDRIA. IT APPEARS THAT FAT INTAKE REVERSES THE BENEFICIAL EFFECTS OF CALORIC RESTRICTION ON ROS PRODUCTION. HIGH FRUCTOSE DIET INCREASES OF H2O2 RELEASED BY MITOCHONDRIA, THAT CAN BE PREVENTED BY GLISODIN® A VEGETABLE SUPEROXIDE DISMUTASE (SOD) SUPPLEMENT. HYPEROXIC PRECONDITIONING (4 DAYS AT 50% OF O2 FOLLOWED BY 5 DAYS AT 80% OF O2) WOULD REDUCE THE ROS PRODUCTION BY ENHANCING CYTOCHROME C OXYDASE (COX) ACTIVITY.LA PRINCIPALE SOURCE D'ESPECES REACTIVES DE L'OXYGENE (ROS) EST LA MITOCHONDRIE, PAR L'INTERMEDIAIRE DE SA CHAINE RESPIRATOIRE. DEUX PARAMETRES ESSENTIELS PEUVENT MODULER CETTE PRODUCTION : LA NATURE DES EQUIVALENTS REDUITS (NADH,H+ ET FADH2) ET L'APPORT EN OXYGENE. NOUS NOUS SOMMES INTERESSES AUX EFFETS DE REGIMES ALIMENTAIRES (MODIFIANT LA PROPORTION ENTRE NADH,H+ ET FADH2) ET A L'HYPEROXIE (MODIFIANT L'APPORT EN O2) SUR LA PRODUCTION D'H2O2 PAR LES MITOCHONDRIES DE MUSCLE SQUELETTIQUE ET/OU DE FOIE DE RATS. NOUS AVONS MIS EN EVIDENCE QUE LA CONSOMMATION DE LIPIDES SUPPRIME LES EFFETS BENEFIQUES DE LA RESTRICTION CALORIQUE SUR LA PRODUCTION DE ROS. LE REGIME RICHE EN FRUCTOSE AUGMENTE LA QUANTITE D'H2O2 GENEREE PAR LES MITOCHONDRIES, CELLE-CI POUVANT NEANMOINS ETRE PREVENUE PAR UN TRAITEMENT A LA GLISODIN® (CONSTITUEE DE SOD VEGETALE). LE PRECONDITIONNEMENT HYPEROXIQUE (4 JOURS A 50% D'O2 SUIVI DE 5 JOURS A 80% D'O2) DIMINUERAIT LA PRODUCTION DE ROS EN STIMULANT L'ACTIVITE DE LA COX

Fat intake reverses the beneficial effects of low caloric intake on skeletal muscle mitochondrial H(2)O(2) production.

International audienceFood restriction is the most effective modulator of oxidative stress and it is believed that a reduction in caloric intake per se is responsible for the reduced generation of reactive oxygen species (ROS) by mitochondria. Hydrogen peroxide (H(2)O(2)) generation and oxygen consumption (O(2)) by skeletal muscle mitochondria were determined in a peculiar strain of rats (Lou/C) characterized by a self-low-caloric intake and a dietary preference for fat. These rats were fed either with a standard high-carbohydrate (HC) or a high-fat (HF) diet and the results were compared to those measured in Wistar rats fed a HC diet. H(2)O(2) production was significantly reduced in Lou/C rats fed a HC diet; this effect was not due to a lower O(2) consumption but rather to a decrease in rotenone-sensitive NADH-ubiquinone oxidoreductase activity and increased expression of uncoupling proteins 2 and 3. The reduced H(2)O(2) generation displayed by Lou/C rats was accompanied by a significant inhibition of permeability transition pore (PTP) opening. H(2)O(2) production was restored and PTP inhibition was relieved when Lou/C rats were allowed to eat a HF diet, suggesting that the reduced oxidative stress provided by low caloric intake is lost when fat proportion in the diet is increased

High dietary sucrose triggers hyperinsulinemia, increases myocardial beta-oxidation, reduces glycolytic flux and delays post-ischemic contractile recovery.

International audienceAlthough the causal relationship between insulin resistance (IR) and hypertension is not fully resolved, the importance of IR in cardiovascular dysfunction is recognized. As IR may follow excess sucrose or fructose diet, the aim of this study was to test whether dietary starch substitution with sucrose results in myocardial dysfunction in energy substrate utilization and contractility during normoxic and post-ischemic conditions. Forty-eight male Wistar rats were randomly allocated to three diets, differing only in their starch to sucrose (S) ratio (13, 2 and 0 for the Low S, Middle S and High S groups, respectively), for 3 weeks. Developed pressure and rate x pressure product (RPP) were determined in Langendorff mode-perfused hearts. After 30 min stabilization, hearts were subjected to 25 min of total normothermic global ischemia, followed by 45-min reperfusion. Oxygen consumption, beta-oxidation rate (using 1-13C hexanoate and Isotopic Ratio Mass Spectrometry of CO2 produced in the coronary effluent) and flux of non-oxidative glycolysis were also evaluated. Although fasting plasma glucose levels were not affected by increased dietary sucrose, high sucrose intake resulted in increased plasma insulin levels, without significant rise in plasma triglyceride and free fatty acid concentrations. Sucrose-rich diet reduced pre-ischemic baseline measures of heart rate, RPP and non-oxidative glycolysis. During reperfusion, post-ischemic recovery of RPP was impaired in the Middle S and High S groups, as compared to Low S, mainly due to delayed recovery of developed pressure, which by 45 min of reperfusion eventually resumed levels matching Low S. At the start of reperfusion, delayed post-ischemic recovery of contractile function was accompanied by: (i) reduced lactate production; (ii) decreased lactate to pyruvate ratio; (iii) increased beta-oxidation; and (iv) depressed metabolic efficiency. In conclusion, sucrose rich-diet increased plasma insulin levels, in intact rat, and increased cardiac beta-oxidation and coronary flow-rate, but reduced glycolytic flux and contractility during normoxic baseline function of isolated perfused hearts. Sucrose rich-diet impaired early post-ischemic recovery of isolated heart cardiac mechanical function and further augmented cardiac beta-oxidation but reduced glycolytic and lactate flux