[Self medication with Annona muricata L. (corossol) as an anti-cancer agent in Reunion]. / Automédication par Annona muricata L. (corossol) à visée anticancéreuse à la Réunion.

INTRODUCTION: Annona muricata L. also called soursop, graviola, guanabana and sapoty (French creole) is a fruit tree growing in tropical countries. The fruits, seeds, leaves and roots are used in traditional medicine. Potential anticancer effects encourage patients to consume this product as self medication. The object of the study was to determine the prevalence of use of graviola as an anticancer agent by patients treated for a lung cancer. METHODS: Our survey took place in two thoracic oncology day cares units of the university hospital of Reunion. All the patients treated by chemotherapy and immunotherapy for lung cancer were asked the same questions in a face to face interview over a 6-month period. RESULTS: One hundred questionnaires were collected. Sixty seven patients consumed graviola. In 53.7%, graviola was consumed as an anticancer agent and 25 patients took it regularly. Most often graviola was ingested as an infusion of boiled leaves (69.5%). The supply was exclusively local. CONCLUSIONS: A quarter of patients treated by chemotherapy for a lung cancer in Reunion consume graviola regularly as self medication. The consequences of this intake, drug interactions and side effects are unknown and would be interesting to identify.

Time course of asymmetric dimethylarginine (ADMA) and oxidative stress in fructose-hypertensive rats: a model related to metabolic syndrome.

OBJECTIVE: Asymmetric dimethylarginine (ADMA) is an endogenous modulator of endothelial function and oxidative stress, and increased levels of this molecule have been reported in some metabolic disorders and cardiovascular diseases. The aim of this work was to analyze the time course of dimethylarginine compounds and oxidative stress levels and the relationship between these and cardiovascular function in fructose-hypertensive rats. METHODS AND RESULTS: 90 male Sprague-Dawley rats were randomized into 2 groups, fed for 3 months with standard (C) chow supplemented or not with fructose (F, 60%). After sacrifice at different weeks (W), the aorta and plasma were harvested to assess the vascular and biochemical parameters. Our work showed that the plasma levels of ADMA in the fructose-fed rats increased after 2 weeks of the diet (1.6 ± 0.3 µM vs. 1.2 ± 0.3 µM, p < 0.05) with no changes in plasma levels of either SDMA or L-arginine and after an increase in glycemia. Levels of vascular oxidative stress, estimated in aortic segments using an oxidative fluorescence technique, were higher in the F group (W2: 1.14 ± 0.2% vs. 0.33 ± 0.02%, p < 0.01). An increase in expression levels of nitrotyrosine (3-fold) and iNOS (2-fold) were noted in the fructose-fed rats. After 1 month, this was associated with a significant increase in NAD(P)H oxidase activity. Concerning vascular function, a 15% decrease in maximal endothelium-dependent relaxation was found in the aorta of the F group. Our work showed that the presence of exogenous L-MMA, an inhibitor of NO synthase, was associated with a significant reduction in endothelium-dependent relaxation in isolated aorta rings of the C group; this effect was not observed in the vessels of fructose-fed rats. CONCLUSION: Our findings suggest that the elevated levels of ADMA observed could in part be secondary to the early development of oxidative stress associated with the development of hypertension.

Dietary n-3 polyunsaturated fatty acids and coronary heart disease-related mortality: a possible mechanism of action.

Epidemiological and interventional studies indicate that dietary n-3 PUFA reduces mortality due to coronary heart disease (CHD). They act at a low dose, since one or two meals with fatty fish per week is sufficient to provide protection when compared with no fish intake. These fatty acids are effective in providing primary prevention in low- and high-risk subjects and secondary prevention. At high doses, dietary n-3 PUFAs have several beneficial properties. First, they act favourably on blood characteristics: they are hypocholesterolemic and hypotriglyceridemic; they reduce platelet aggregation; they exhibit antithrombotic and fibrinolytic activities; they reduce blood viscosity and they exhibit antiinflammatory action. Second, they reduce ischemia/reperfusion-induced cellular damage. This effect is apparently due to the incorporation of eicosapentaenoic acid in membrane phospholipids. Third, they reduce ischemia and reperfusion arrhythmias. All the effects exerted by n-3 PUFAs at high doses are incompatible with the beneficial action on CHD mortality in humans observed at low doses, where their main properties are related to circulation in the form of free fatty acids. Numerous experimental studies have indicated that low concentrations of exogenous n-3 PUFAs reduce the severity of cardiac arrhythmias. This effect is probably responsible for the protective action of n-3 PUFA on CHD mortality. Further studies are necessary to confirm this assumption in animals. Such studies should take account of the fact that only a low dose of n-3 PUFA (20 mg/kg/day) is necessary to afford protection. Furthermore, since the beneficial effect of n-3 PUFAs on CHD mortality is observed in fish eaters versus no-fish eaters, and since populations in industrialised countries consume excess n-6 PUFAs, control animals in long-term dietary experiments should be fed a diet with only n-6 fatty acids as a source of PUFAs.

Effects of dietary polyunsaturated fatty acids and hepatic steatosis on the functioning of isolated working rat heart under normoxic conditions and during post-ischemic reperfusion.

The purpose of this study was to modify the amount of 22:4 n-6, 22:5 n-6 and 20:5 n-3 in cardiac phospholipids and to evaluate the influence of these changes on the functioning of working rat hearts and mitochondrial energy metabolism under normoxic conditions and during postischemic reperfusion. The animals were fed one of these four diets: (i) 10% sunflower seed oil (SSO); (ii) 10% SSO + 1% cholesterol; (iii) 5% fish oil (FO, EPAX 3000TG, Pronova) + 5% SSO; (iv) 5% FO + 5% SSO + 1% cholesterol. Feeding n-3 PUFA decreased n-6 PUFA and increased n-3 PUFA in plasma lipids. In the phospholipids of cardiac mitochondria, this dietary modification also induced a decrease in the n-6/n-3 PUFA ratio. Cholesterol feeding induced marked hepatic steatosis (HS) characterized by the whitish appearance of the liver. It also brought about marked changes in the fatty acid composition of plasma and mitochondrial phospholipids. These changes, characterized by the impairment of deltaS- and delta6-desaturases, were more obvious in the SSO-fed rats, probably because of the presence of the precursor of the n-6 family (linoleate) in the diet whereas the FO diet contained large amounts of eicosapentaenoic and docosahexaenoic acids. In the mitochondrial phospholipids of SSO-fed rats, the (22:4 n-6 + 22:5 n-6) to 18:2 n-6 ratio was decreased by HS, without modification of the proportion of 20:4 n-6. In the mitochondrial phospholipids of FO-fed rats, the amount of 20:5 n-3 tended to be higher (+56%). Cardiac functioning was modulated by the diets. Myocardial coronary flow was enhanced by HS in the SSO-fed rats, whereas it was decreased in the FO-fed animals. The rate constant k012 representing the activity of the adenylate kinase varied in the opposite direction, suggesting that decreased ADP concentrations could cause oxygen wasting through the opening of the permeability transition pore. The recovery of the pump function tended to be increased by n-3 PUFA feeding (+22%) and HS (+45%). However, the release of ascorbyl free radical during reperfusion was not significantly modified by the diets. Conversely, energy production was increased by ischemia/reperfusion in the SSO group, whereas it was not modified in the FO group. This supports greater ischemia/reperfusion-induced calcium accumulation in the SSO groups than in the FO groups. HS did not modify the mitochondrial energy metabolism during ischemia/reperfusion. Taken together, these data suggest that HS- and n-3 PUFA-induced decrease in 22:4 and 22:5 n-6 and increase in 20:5 n-3 favor the recovery of mechanical activity during post-ischemic reperfusion.

Dietary n-3 polyunsaturated fatty acids affect the development of renovascular hypertension in rats.

The consequences of a dietary n-3 PUFA supply was investigated on the blood pressure (BP) increase elicited by left renal artery stenosis in rats distributed in 3 groups (n = 8) fed for 8 weeks a semi-purified diet either as control diet or enriched diets (docosahexaenoic acid, DHA, or eicosapentaenoic acid, EPA). The PUFA intake induced large alterations in heart and kidney phospholipid fatty acid profile, but did not influence body weight, cardiac hypertrophy, renal left atrophy and right hypertrophy. Within 4 weeks, BP raised from 120-180 +/- 2 mm Hg in the control group, but only to 165 +/- 3 mm Hg in the n-3 PUFA groups. After stabilization of BP in the 3 groups, the rats received a short administration of increasing dose of perindopril. The lower dose (0.5 mg/kg) moderately decreased BP only in the control group. With higher doses (1, 5 and 10 mg/kg) BP was normalized in the 3 groups, with a higher amplitude of the BP lowering effect in the control group. A moderate n-3 PUFA intake can contribute to prevent the development of peripheral hypertension in rats by a mechanism that may involve angiotensin converting enzyme.

Is a dietary n-3 fatty acid supplement able to influence the cardiac effect of the psychological stress?

Epidemiological studies suggest that n-3 polyunsaturated fatty acids (PUFA) are involved in the prevention of cardiovascular disease. Stress is known to increase the incidence of CVD and the present study was realised to evaluate some physiological and biochemical effects of dietary docosahexaenoic acid (DHA) in male Wistar rats subjected to a psycho social stress. Rats were fed for 8 weeks a semi-purified diet containing 10% of either sunflower seed oil or the same oil supplemented with DHA. This food supply represented 50% of their daily requirement. The remaining 50% were supplied as 45 mg food pellets designed to induce stress in rats by an intermittent-feeding schedule process. The control group (n = 12) was fed the equivalent food ration as a single daily feeding. The physiological cardiovascular parameters were recorded by telemetry through a transmitter introduced in the abdomen. At the end of the experimentation, the heart and adrenals were withdrawn and the fatty acid composition and the catecholamine store were determined. Dietary DHA induced a pronounced alteration of the fatty acid profile of cardiac phospholipids (PL). The level of all the n-6 PUFAs was reduced while 22:6 n-3 was increased. The stress induced a significant increase in heart rate which was not observed in DHA-fed group. The time evolution of the systolic blood pressure was not affected by the stress and was roughly similar in the stressed rats of either dietary group. Conversely, the systolic blood pressure decreased in the unstressed rats fed DHA. Similar data were obtained for the diastolic blood pressure. The beneficial effect of DHA was also observed on cardiac contractility, since the dP/dt(max) increase was prevented in the DHA-fed rats. The stress-induced modifications were associated with an increase in cardiac noradrenaline level which was not observed in DHA-fed rats. The fatty acid composition of adrenals was significantly related to the fatty acid intake particularly the neutral lipid fraction (NL) which incorporated a large amount of DHA. Conversely, n-3 PUFAs were poorly incorporated in adrenal phospholipids. Moreover the NL/PL ratio was significantly increased in the DHA fed rats. The amount of adrenal catecholamines did not differ significantly between the groups. These results show that a supplementation of the diet with DHA induced cardiovascular alterations which could be detected in conscious animals within a few weeks. These alterations were elicited by a reduced heart rate and systolic and diastolic blood pressure.

Effects of electromyostimulation and strength training on muscle soreness, muscle damage and sympathetic activation.

Electromyostimulation (EMS) is known to develop muscular strength and hypertrophy. The aim of this study was to compare EMS exercise-induced damage with concentric (CONC) exercise-induced damage. Twelve male athletes were randomly assigned to concentric exercise (five sets of 6 voluntary contractions) or to EMS (30 contractions of 6 s duration, 20 s rest between contractions) on day 0 (D0). The load was 80% of the maximal isometric force. Criterion measures of plasma creatine kinase (CK) activity and lactate dehydrogenase (LDH) activity, and subjective ratings of muscle soreness and urinary catecholamines, were assessed 1 day before and for 3 days after exercise. Among the members of the EMS group, there were significant increases in catecholamine urinary excretion, especially adrenaline (on days D+2 and D+3), plasma CK activity (on day D+2) and plasma LDH activity (on days D+1 and D+2). The changes among the members of the CONC group were smaller and no significant difference was noted. Muscular soreness was greatest in the EMS group, with the peak occurring on day D+2. Comparisons of enzyme release, muscular soreness and urinary catecholamines suggest that EMS induces myofibre membrane damage and a significant increase in sympathetic nervous activity.

Influence of the phospholipid n-6/n-3 polyunsaturated fatty acid ratio on the mitochondrial oxidative metabolism before and after myocardial ischemia.

The influence of dietary n-6 and n-3 polyunsaturated fatty acids (PUFA) on heart pump function and mitochondrial energy metabolism was investigated before and after ischemia. Weanling male Wistar rats were fed for 8 weeks a diet containing either 10% of sunflower seed oil (SSO group) or 10% of a 1:1 (w/w) mixture of fish oil and sunflower seed oil (FO group). The hearts were perfused according to the working mode for 15 min with a Krebs-Henseleit medium containing glucose (11 mM), insulin (10 IU/L) and caprylic acid (25 microM). They were then either maintained in normoxic conditions (70 min) or subjected to a global no-flow normothermic ischemia (20 min) followed by reperfusion (50 min). The aortic and coronary flows were monitored at 5-min intervals. The lactate dehydrogenase (LDH) release in the coronary effluent was evaluated in the control hearts and during ischemia/reperfusion. At the end of the perfusion, two subpopulations of mitochondria were prepared from each heart, by either mechanical or enzyme extraction (ME and EE mitochondria, respectively). The succinate dehydrogenase (SDH) activity was evaluated. Furthermore, the respiration parameters were assessed with either glutamate (20 mM) or palmitoylcarnitine (25 microM) as substrate. Substituting sunflower seed oil by fish oil in the diet provoked a large decrease in the n-6/n-3 PUFA ratio of cardiac phospholipids. The n-3 PUFA enrichment did not alter the coronary and aortic flows nor the LDH release in physiological conditions. Conversely, during post-ischemic reperfusion, the increased amount of n-3 PUFA improved the recovery of aortic flow and decreased the LDH release, without affecting significantly the coronary flow. In ME and EE mitochondria, the phospholipid n-6/n-3 PUFA ratio was similarly modified by the dietary manipulations. The analysis of total cardiac SDH activity suggested an ischemia-induced oedema, of similar magnitude in the two dietary groups. However, neither dietary manipulations nor ischemia influenced the mitochondrial extraction. Similarly, the parameters of glutamate oxidation were also unaffected. Conversely, with palmitoylcarnitine, post-ischemic reperfusion induced a decrease in both state III respiration rate and energy production which were more important in the EE mitochondria of the SSO group. These results suggest that the recovery of mitochondrial energy metabolism and myocardial pump function during reperfusion may be improved in n-3 PUFA-rich hearts. This could be related to a lower injury in n-3 PUFA-rich membranes. Since cardiac function in physiological conditions was not affected by the diet, fish oil could be considered as a beneficial factor to limit heart injury during ischemia and reperfusion.

[Effects of the level of polyunsaturated fatty acids of the diet on the functioning and depletion of energy substrates in the rat heart during perfusion by left atrial route]. / Effets de la teneur en acides gras polyinsaturés du régime sur le fonctionnement et la déplétion en substrats énergétiques de coeur de rat au cours de la perfusion par voie atriale gauche.

The effects of semi-liquid diets containing 6.6% in weight of refined sunflower seed oil (SSO) or hydrogenated coconut oil (HCO) on cardiac endogenous substrates and functional parameters of rats hearts were compared to a standard laboratory chow during seven days. No difference appeared for cardiac glycogen and lipid constituents. Cardiac performance, measured through left atrial perfusion was enhanced by SSO diet and HCO one altered it. A significative phospholipid depletion appeared during the 45 minutes perfusion only in the HCO group.

Evaluation of pyridoxine intake and pyridoxine status among aged institutionalised people.

The vitamin B6 status of 60 institutionalised elderly subjects (group A: 31 men, mean age = 77 yr and 29 women, mean age = 84 yr) and 41 healthy young adults (group B or control group: 18 men, mean age = 30 yr and 23 women, mean age = 27 yr) was evaluated using erythrocyte aspartate aminotransferase activity coefficient (alpha EGOT) and plasma pyridoxal phosphate (PLP) level (vitamin B6-deficient subjects = alpha greater than 2.0 and PLP less than 80 nmol/l). The kilocalorie, protein and pyridoxine intakes were also estimated. Regarding calories and protein, the diets may be generally considered satisfactory in respect to the French 1981 RDA. The mean dietary intake of vitamin B6 was less than 2 mg/day in all groups. Ninety per cent of the aged, 80 per cent of females in group B in contrast to 56 per cent of males in group B consumed less than their individual vitamin B6 requirements as determined by a probability method. As the incidence of vitamin B6 biochemical deficiency was much higher in the group A (71% for males and 86% for females) than in the control group (11% for males and 30% for females), it is concluded that the high incidence of biochemical vitamin B6 deficiency noted in the aged appeared more relevant from an altered metabolism of the vitamin than from a too low energy intake. Supplements with high doses of vitamin B6 to aged subjects caused a significant decrease in alpha EGOT and a significant increase in PLP levels.