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Women have a lower incidence of cardiovascular diseases (CVD) than men at a similar age but the reverse is the case after menopause, indicating a possible protective effect of estrogen on cardiometabolic function. Although various hormonal therapies have been formulated to combat the CVD risks in postmenopausal state, the beneficial effects have not been consistent. Obesity with insulin resistance (IR) is closely linked to CVD risks while ovariectomized rodents have been shown to mimic a state of obesity and IR. We therefore hypothesized that low-dose spironolactone would ameliorate obesity and IR in estrogendeprived rats by replenishing estrogen and suppressing elevated glycogen synthase kinase-3 (GSK-3). Ten-week-old female Wistar rats were divided into 4 groups: sham-operated (SHM), spironolactone (SPL; 0.25 mg/kg), and ovariectomized (OVX) rats treated with or without spironolactone daily for 8 weeks. Results showed that estrogen deprivation through ovariectomy caused increased body mass gain and visceral adiposity that are accompanied by increased HOMA-IR, HOMA-[beta], 1-hour postload glucose, glucose intolerance, platelet/lymphocyte ratio, plasma insulin, atherogenic dyslipidemia, uric acid, GSK-3, corticosterone, and aldosterone and depressed 17[beta]-estradiol. However, treatment of OVX rats with spironolactone ameliorated all these effects. Taken together, the results demonstrate that treatment with low-dose spironolactone improves obesity and IR, which appears to involve replenishment of estrogen and suppression of GSK-3 along with circulating mineralocorticoid and glucocorticoid. The findings imply a positive cardiometabolic effect of low-dose spironolactone usage in estrogen-deprived conditions.Key words: aldosterone, cardiometabolic syndrome, estrogen replacement therapy, GSK-3, mineralocorticoid receptor, spironolactone.Les maladies cardiovasculaires (MCV) sont moins frequentes chez les femmes que chez les hommes d'ages similaires, mais la situation s'inverse apres la menopause, ce qui pointe vers un effet protecteur des aestrogenes sur la fonction cardiometabolique. Bien que diverses presentations de therapies hormonales aient ete proposees en vue de combattre le risque de MCV apres la menopause, les bienfaits obtenus ont ete inegaux. L'obesite avec resistance a l'insuline (RI) est intimement liee aux risques de MCV, et il est decrit que les rongeurs ovariectomises miment un etat d'obesite avec RI. Nous avons donc pose l'hypothese selon laquelle une faible dose de spironolactone permet d'ameliorer l'etat d'obesite avec RI chez des rates carencees en aestrogenes en retablissant les taux d'aestrogenes et en inhibant la hausse de la GSK-3 (pour glycogen synthase kinase-3). Nous avons reparti des rates Wistar de 10 semaines dans 4 groups : intervention factice (<< sham >>), ovariectomie (OVX), ainsi que deux groupes semblables avec en plus l'administration de spironolactone a raison de 0,25 mg/kg quotidiennement pendant 8 semaines. Les resultats ont montre que la carence en aestrogenes provoquee par l'OVX entrainait une augmentation de la prise de poids et une accumulation de tissu adipeux visceral accompagnees d'une augmentation des taux d'HOMA-IR, d'HOMA-[beta], de la glycemie 1 heure apres l'administration d'une charge glycemique, du ratio plaquettes/lymphocytes, des taux plasmatiques d'insuline, d'acide urique, de GSK 3, de corticosterone et d'aldosterone avec un abaissement des taux d'estradiol 17[beta], ainsi qu' intolerance au glucose et une dyslipidemie atherogene. Mais l'administration de spironolactone a permis d'attenuer ces effets chez les rates OVX. Dans l'ensemble, les resultats montrent que l'administration de faibles doses de spironolactone permet d'attenuer l'obesite et la RI, ce qui semble lie au retablissement des taux d'aestrogenes, avec l'inhibition de la GSK-3, ainsi que des taux de mineralocorticoides et de glucocorticoides en circulation. Les resultats pointent vers un effet cardiometabolique avantageux du spironolactone a faible dose utilise en situation de carence en aestrogenes. [Traduit par la Redaction]Mots-cles : aldosterone, syndrome cardiometabolique, therapie de substitution des aestrogenes, GSK-3, recepteur des mineralocorticoides, spironolactone., IntroductionCardiovascular disease (CVD) has been the major cause of death for several decades and is expected to remain so until 2030 (Mathers and Loncar 2006). It has been shown that [...]

Estrogen deficiency has been associated with increased incidence of cardiovascular diseases, and recent clinical trials of standard formulations of hormonal therapies have not demonstrated consistent beneficial effects. Estrogen-progestin therapy has been used as exogenous estrogen to normalize depressed estrogen level during menopause. Ovariectomized rodents mimic an estrogen-deficient state in that they develop cardiometabolic dysfunction, including insulin resistance (IR). We therefore hypothesized that hormonal therapy with combined oral contraceptive steroids, ethinylestradiol-levonorgestrel (EEL), improves IR, obesity, and glycogen synthase kinase-3 (GSK-3) through reduction of circulating mineralocorticoid in ovariectomized rats. Twelve-week-old female Wistar rats were divided into 4 groups: sham-operated (SHM) and ovariectomized (OVX) rats were treated with or without EEL (1.0 [micro]g ethinylestradiol and 5.0 [micro]g levonorgestrel) daily for 8 weeks. Results showed that OVX or SHM + EEL treated rats had increased HOMA-IR (homeostatic model assessment of IR), 1 h postload glucose, HOMA-[beta], triglycerides (TG), total cholesterol (TC), TC/HDL cholesterol, TG/HDL cholesterol, plasma insulin, GSK-3, corticosterone, and aldosterone. On the other hand, OVX + EEL treatment ameliorated all these effects except that of aldosterone. Taken together, the results demonstrate that oral hormonal replacement with EEL improves IR and pancreatic [beta]-cell function and suppresses GSK-3 and glucocorticoid independent of circulating aldosterone, suggesting a positive cardiometabolic effect of oral EEL therapy in estrogen-deficient rats. Key words: cardiometabolic syndrome, oral contraceptive, hormone replacement therapy, GSK-3, aldosterone. On a associe le deficit en restrogenes a une augmentation de l'incidence des maladies cardiovasculaires, et de recents essais cliniques portant sur des presentations standard d'hormonotherapies n'ont pas montre d'effets avantageux consequents. Le traitement par l'association d'restrogenes avec des progestatifs a ete utilise en tant qu'restrogenes exogenes en vue de ramener les taux d'restrogenes deprimes a la normale pendant la menopause. L'ovariectomie chez le rongeur est un modele de deficit restrogenique par la formation d'un dysfonctionnement cardiometabolique, y compris une resistance a l'insuline (RI). Par consequent, nous avons formule une hypothese selon laquelle la combinaison d'une hormonotherapie avec des steroides contraceptifs oraux--ethinylestradiol-levonorgestrel (EEL)--permet d'attenuer la RI, l'obesite et l'effet de la GSK-3 (glycogen synthase kinase-3) par la diminution des taux de mineralocorticoides en circulation chez des rates ovariectomisees. Nous avons reparti des rates Wistar de 12 semaines dans 4 groupes: intervention chirurgicale factice (SHM) ou ovariectomie (OVX) avec ou sans administration quotidienne d'EEL (1,0 [micro]g d'ethinylestradiol et 5,0 [micro]g de levonorgestrel) pendant 8 semaines. Les resultats ont montre que les rates des groupes OVX et SHM + EEL presentaient une hausse de l'HOMA-IR (pour << homeostatic model assessment of insulin resistance >>), de la glycemie 1 h apres l'administration de glucose et de l'HOMA-[beta], ainsi que des taux de triglycerides (TG) et de cholesterol total (CT), des rapports CT/cholesterol HDL et TG/cholesterol HDL, avec une augmentation des taux plasmatiques d'insuline, de GSK-3, de corticosterone et d'aldosterone. Inversement, tous ces effets s'amelioraient dans le groupe OVX + EEL, sauf pour l'aldosterone. Dans l'ensemble, ces resultats montrent que la substitution hormonale avec de l'EEL par voie orale permet d'attenuer la RI et d'ameliorer le fonctionnement des cellules pancreatiques [beta], avec une diminution des taux de GSK-3 et de glucocorticoides independante de l'aldosterone. Cela laisse entrevoir un effet cardiometabolique positif pour le traitement par l'EEL par voie orale chez les rates en deficit restrogenique. [Traduit par la Redaction] Mots-cles: syndrome cardiometabolique, contraceptif oral, traitement par substitution hormonale, GSK-3, aldosterone., Introduction Sexual dimorphisms in the development of cardiovascular diseases (CVDs) are well documented in both human and animal studies. The incidence of CVDs among women increases sharply after menopause (Mendelsohn [...]

We hypothesised that TG/HDL-C ratio and PAI-1 would be associated with high pulse pressure (PP) in young adults with sickle cell trait (SCT) and sickle cell disease (SCD). We compared the clinical, biochemical, and cardiometabolic parameters among individuals with normal genotype (HbAA; n = 60), SCT (HbAS; n = 60), and SCD (HbSS; n = 60), all in steady state. Using multivariate linear regression analysis, high PP was positively related to TG/HDL-C ratio in SCT (β = 0.307; p =.014) and PAI-1 (β = 0.499; p =.001) in SCD. The curve of receiver operating characteristic also showed that TG/HDL-C ratio and PAI-1 are efficient predictors of high PP in SCT carriers and SCD patients, respectively. This study suggests that increased levels of TG/HDL-C ratio and PAI-1 may be salient risk factors that would promote the development of arterial stiffness and other CVD in SCT carriers and SCD patients. [ABSTRACT FROM AUTHOR]

Oral contraceptive (OC) steroids use has been associated with variable effects on blood lipid and rheological properties, and abnormal plasma lipid and hemorheological profiles has been shown to be in almost all conditions associated with accelerated atherosclerotic cardiovascular disorders. This study aimed at investigating the effect of increased calcium intake on plasma levels of lipids, malondialdehyde (lipid peroxidation index), free radical defense system and hemorheological variables in OC-treated female Sprague–Dawley rats. OC-treated and OC+Calcium-treated groups received a combination of ethinyl estradiol and norgestrel for 10 weeks by oral gavage. OC+Calcium-treated rats fed on 2.5% calcium diet while other groups fed on 0.9% calcium diet in addition to drinking water ad libitum. Results showed that LDL-cholesterol, total cholesterol/HDL-cholesterol ratio, LDL-cholesterol/HDL-cholesterol ratio, plasma viscosity, hematocrit and plasma fibrinogen were significantly higher while plasma HDL-cholesterol, 17β-estradiol, testosterone and calcium levels were significantly lower in OC-treated rats when compared with the control rats. The altered plasma lipid and calcium levels were prevented by increased calcium intake, whereas the OC-induced changes in hematocrit, plasma viscosity, fibrinogen, 17β-estradiol and testosterone were not affected by increased dietary calcium. Plasma lipid peroxidation index, ascorbic acid and albumin levels were comparable in all the groups. The present study demonstrated that OC-induced altered blood lipid and rheological properties were not associated with increased lipid peroxidation. The results also suggest that calcium enriched diet may improve lipid profile but not hemorheological parameters, by a mechanism that is independent of circulating 17β-estradiol and testosterone in OC-treated rats. [ABSTRACT FROM AUTHOR]

The effect of oral administration of an aqueous extract of Hibiscus sabdariffa Linn petals on Na + -K + -ATPase and Ca 2+ -Mg 2+ -ATPase activities of rat heart have been investigated in Sprague-Dawley rats. The extract was administered orally in doses of 25.0 and 50.0 mg/kg body weight for 28 days. Results showed that Hibiscus sabdariffa treatment led to significant increases (p [ABSTRACT FROM AUTHOR]

The antidiabetic activity of the cashew plant ( Anacardium occidentale Linn. [Anacardiaceae]) stem-bark methanol extract was investigated in fructose-fed (diabetic) and normal rats. Animals were randomly divided into group A (control), group B (treated with 200.0 mg/kg body weight of the extract; orally), group C (fed with enriched fructose diet only, 25%; w/w) and group D (fed with enriched fructose diet along with 200.0 mg/kg body weight of the extract; orally). Animals were treated with extract and/or enriched fructose diet for 21 days. The enriched fructose diet resulted in significant increases in plasma glucose, total cholesterol, triglyceride, total cholesterol/HDL-cholesterol ratio, malonyldialdehyde, total protein, urea, and creatinine. Administration of the extract significantly prevented changes in plasma glucose, triglyceride, total cholesterol/HDL-cholesterol ratio, malonyldialdehyde, urea, and creatinine induced by enriched fructose diet. On the other hand, treatment with enriched fructose diet and/or extract did not have any significant effect on plasma alkaline phosphatase level. These results show that chronic oral administration of methanol extract of Anacardium occidental stem-bark at a dose of 200.0 mg/kg body weight may be a safe alternative antihyperglycemic agent that has beneficial effect by improving plasma glucose and lipids in fructose-induced diabetic rats, which is associated with a reduced lipid peroxidation. [ABSTRACT FROM AUTHOR]

The effects of administrating aqueous extracts of the petals of red and green Hibiscus sabdariffa (1.0 and 1.5 mg/kg body weight) on hematological and plasma lipid variables were examined in rats. Animals were randomly divided into group A (control), groups B and C (treated with 1.0 and 1.5 mg/kg body weight, respectively, of the extract of petals of red Hibiscus sabdariffa ), and groups D and E (treated with 1.0 and 1.5 mg/kg body weight, respectively, of the extract of petals of green Hibiscus sabdariffa ). The chronic administration of both extracts for 28 days resulted in significant decreases in the plasma total cholesterol levels at 1.5 mg/kg body weight (p 0.05). These results indicate that the lowered plasma total cholesterol concentrations induced by aqueous extracts of either red or green Hibiscus sabdariffa petals is strongly associated with decreased LDL-cholesterol concentrations. Thus, both extracts could exert similar cardiovascular protective effects. [ABSTRACT FROM AUTHOR]

The antidiabetic and antilipidemic effects of Bougainvillea glabra was investigated in this study using 25 male wistar rats. The rats were divided into 5 groups comprising of five animals each. These groups include a normal control (administered saline), an extract control (administered 100 mg/kg of extract) and a diabetic control (untreated group). The remaining two groups were administered 100mg/kg and 400 mg/kg of the extract respectively. The study lasted for three weeks although blood samples were obtained from the rat tails after every week. The results show that the extract significantly (p< 0.05) reduced the hyperglycaemia from 12±0.40 mmol/L (Diabetic Control) to 4.04±0.03 mmol/L (400 mg/kg group). Likewise, the extract significantly reduced the Total Cholesterol (TC), Triglyceride (TG) and Low-Density Lipoprotein Cholesterol (LDLCholesterol), while increasing the High-Density Lipoprotein Cholesterol (HDL-C). In conclusion, the observations from this study show that Bougainvillea glabra has antidiabetic effect and beneficial effects on blood lipid profile, thus justifying the use of the plant by traditional medicine practitioners for the treatment of diabetes mellitus. [ABSTRACT FROM AUTHOR]