Supplementing Soy-Based Diet with Creatine in Rats: Implications for Cardiac Cell Signaling and Response to Doxorubicin.

Nutritional habits can have a significant impact on cardiovascular health and disease. This may also apply to cardiotoxicity caused as a frequent side effect of chemotherapeutic drugs, such as doxorubicin (DXR). The aim of this work was to analyze if diet, in particular creatine (Cr) supplementation, can modulate cardiac biochemical (energy status, oxidative damage and antioxidant capacity, DNA integrity, cell signaling) and functional parameters at baseline and upon DXR treatment. Here, male Wistar rats were fed for 4 weeks with either standard rodent diet (NORMAL), soy-based diet (SOY), or Cr-supplemented soy-based diet (SOY + Cr). Hearts were either freeze-clamped in situ or following ex vivo Langendorff perfusion without or with 25 μM DXR and after recording cardiac function. The diets had distinct cardiac effects. Soy-based diet (SOY vs. NORMAL) did not alter cardiac performance but increased phosphorylation of acetyl-CoA carboxylase (ACC), indicating activation of rather pro-catabolic AMP-activated protein kinase (AMPK) signaling, consistent with increased ADP/ATP ratios and lower lipid peroxidation. Creatine addition to the soy-based diet (SOY + Cr vs. SOY) slightly increased left ventricular developed pressure (LVDP) and contractility dp/dt, as measured at baseline in perfused heart, and resulted in activation of the rather pro-anabolic protein kinases Akt and ERK. Challenging perfused heart with DXR, as analyzed across all nutritional regimens, deteriorated most cardiac functional parameters and also altered activation of the AMPK, ERK, and Akt signaling pathways. Despite partial reprogramming of cell signaling and metabolism in the rat heart, diet did not modify the functional response to supraclinical DXR concentrations in the used acute cardiotoxicity model. However, the long-term effect of these diets on cardiac sensitivity to chronic and clinically relevant DXR doses remains to be established

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Is oxidative stress induced by iron status associated with gestational diabetes mellitus?

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Régime riche en graisses de courte et longue durées sur le fonctionnement cardiaque ex vivo en association avec le stress oxydant et le métabolisme énergétique

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Iron and Oxidative Stress in Gestational Diabetes

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Effects of di(2-ethylhexyl)phthalate on testicular oxidant/antioxidant status in selenium-deficient and selenium-supplemented rats.

International audienceDi(ethylhexyl)phthalate (DEHP), the most widely used plasticizer, was investigated to determine whether an oxidative stress process was one of the underlying mechanisms for its testicular toxicity potential. To evaluate the effects of selenium (Se), status on the toxicity of DEHP was further objective of this study, as Se is known to play a critical role in testis and in the modulation of intracellular redox equilibrium. Se deficiency was produced in 3-weeks-old Sprague-Dawley rats feeding them ≤0.05 mg Se /kg diet for 5 weeks, and Se-supplementation group was on 1 mg Se/kg diet. DEHP-treated groups received 1000 mg/kg dose by gavage during the last 10 days of the feeding period. Activities of antioxidant selenoenzymes [glutathione peroxidase 1 (GPx1), glutathione peroxidase 4 (GPx4), thioredoxin reductase (TrxR)], catalase (CAT), superoxide dismutase (SOD), and glutathione S-transferase (GST); concentrations of reduced glutathione (GSH), oxidized glutathione (GSSG), and thus the GSH/GSSG redox ratio; and thiobarbituric acid reactive substance (TBARS) levels were measured. DEHP was found to induce oxidative stress in rat testis, as evidenced by significant decrease in GSH/GSSG redox ratio (>10-fold) and marked increase in TBARS levels, and its effects were more pronounced in Se-deficient rats with ∼18.5-fold decrease in GSH/GSSG redox ratio and a significant decrease in GPx4 activity, whereas Se supplementation was protective by providing substantial elevation of redox ratio and reducing the lipid peroxidation. These findings emphasized the critical role of Se as an effective redox regulator and the importance of Se status in protecting testicular tissue from the oxidant stressor activity of DEHP. © 2011 Wiley Periodicals, Inc. Environ Toxicol, 2011

Green tea extract decreases oxidative stress and improves insulin sensitivity in an animal model of insulin resistance, the fructose-fed rat.

International audienceTea polyphenols, as both insulin potentiating factors and antioxidants, are postulated to act in preventing the metabolic syndrome, which is characterized by insulin resistance, dyslipidemia, and increased oxidative stress

: Lipid lowering drugs and selenium

International audienceThis secondary analysis of "Etude du Vieillissement Art?el" (EVA) study reports the effect of fibrates and statins on plasma selenium concentration and its 9-year change in free-living dyslipidemic elderly. Dyslipidemic patients were categorized in three sub-groups according to final low-density lipoprotein (LDL)-cholesterol level or hypolipidemic treatment: non-treated dyslipidemic (LDL-cholesterol >4.41mmol/L, n=84); dyslipidemics who were treated exclusively by fibrates (n=47) or by statins (n=25) whatever their serum LDL-cholesterol concentration. The influence of lipid-lowering treatments on plasma selenium concentrations and its 9-year change was evaluated by analysis of variance (ANOVA) and multivariate linear regression models taking into account cardiovascular risk and changes in lipid-profile parameters. Multivariate linear regression indicated that the plasma selenium decline was associated with the longitudinal variation in LDL (beta=-0.039+/-0.019, p=0.04) and high-density lipoprotein (HDL)-cholesterol concentrations (beta=0.187+/-0.059, p=0.002) but not with triglycerides (beta=-0.018+/-0.031, p=0.57). During the 9-year follow-up, similar plasma selenium declines were observed in all the sub-groups (p=0.33) despite plasma selenium levels being higher in fibrate users and lower in statin users (p=0.0004). The mechanisms underlying these data are not yet totally understood, but considering the risk of selenium deficiency in the elderly and its relationship with poor health status further clinical trial is needed to verify the proposed hypotheses

Effets du L-Lactate de magnésium alimentaire sur la fonction du myocarde et la masse musculaire chez le rongeur sain

poster commentéDans l’organisme, le L-Lactate est pris en charge par la déshydrogénase qui, en le transformant en pyruvate, produit des équivalents réduits et pourrait être impliqué dans la lutte contre le stress oxydant. L’objectif de notre travail consistait à savoir l’effet de cette molécule sur la fonction du cœur et la masse musculaire quand elle est administrée par voie alimentaire chez le rongeur sain et sédentaire. Des rats mâles ont absorbé à leur convenance une solution de L-Lactate de magnésium pendant 3 mois. L’activité mécanique du cœur a alors été mesurée par échographie. Les cœurs ont ensuite été perfusés selon le mode Langendorff dans des conditions parfaitement standard et la masse des muscles de la patte arrière a été estimée. Enfin, le stress oxydant a été déterminé dans le cœur et dans le plasma. Les animaux ont consommé de façon régulière une faible dose de L-Lactate (28 nmoles/Kg/J). Le composé n’a modifié ni le gain de poids corporel, ni les masses grasses et maigres. Il a accru la masse du tibialis antérieur (+12%). Il a réduit la longueur du ventricule gauche en diastole, mais n’a pas affecté la fraction d’éjection systolique in vivo. Dans le cœur isolé, il a accru les vitesses de contraction (+33%) et de relaxation (+21%) du myocarde, sans altérer le débit coronaire. Au niveau du plasma, il a réduit le stress oxydant des protéines sans altérer celui des lipides. En conclusion, le L-Lactate de magnésium mime les effets de l’entraînement physique régulier chez les animaux sédentaires sur le muscle squelettique et le cœur, peut être en réduisant le stress oxydant plasmatiqu