RESUMO
Context: Studies have shown that cardiac triglyceride accumulation and impaired Na+-K+-ATPase activity are linked to diabetes- related cardiovascular disease, particularly in women.Objectives: We hypothesised that allopurinol (ALL) and valproic acid (VPA) treatment would improve cardiac triglyceride and Na+-K+-ATPase activity independent of circulating aldosterone in Combined Oral Contraceptive (COC)-induced dysglycemiaMaterials and methods: Rats received COC (1.0 µg ethinylestradiol and 5.0 µg levonorgestrel; po) with or without ALL (1 mg; po) and VPA (20 mg; po) for 6 weeks.Results: COC-treatment led to impaired glucose tolerance, accumulated abdominal fat, dyslipidemia, elevated plasma MDA, PAI-1 and aldosterone levels and also reduced plasma nitric oxide bioavailability and cardiac Na+-K+-ATPase activity. However, either ALL or VPA treatment ameliorated these alterations comparably independent of elevated aldosterone levelDiscussion and conclusion: Our results suggest that either ALL or VPA would improve cardiac TG and Na+-K+-ATPase activity comparably in COC-treated rats, regardless of circulating aldosterone level.
Assuntos
Intolerância à Glucose , Resistência à Insulina , Adenosina Trifosfatases , Aldosterona , Alopurinol/farmacologia , Animais , Anticoncepcionais Orais Combinados , Feminino , Humanos , Levanogestrel , Óxido Nítrico , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Ratos , Ratos Wistar , ATPase Trocadora de Sódio-Potássio , Triglicerídeos , Ácido Valproico/farmacologiaRESUMO
The kidney plays a critical role in human health and deviation from its normal function can lead to severe morbidity and mortality. Exposure to excess testosterone in women has been linked to several disorders, including kidney disorder and acting undoubtedly through androgen receptor (AR), whereas the involvement of mineralocorticoid receptor (MR) is unclear. Likewise, the renal effect of sodium acetate (SAc) during late gestational exposure to testosterone is not well known. We hypothesized that SAc or MR blockade would protect the kidney of testosterone-exposed pregnant rats against glutathione and adenosine depletion. Twenty-five pregnant Wistar rats were treated (sc) with olive oil, testosterone propionate (0.5 mg/kg) singly or in combination with SAc (200 mg/kg; p.o.), androgen receptor (AR) blocker, flutamide (Flu; 7.5 mg/kg; p.o.) or (MR) blocker, eplerenone (Eple; 0.5 mg/kg) between gestational days 14 and 19. Glutathione, adenosine and nitric oxide were decreased while uric acid (UA), xanthine oxidase (XO), malondialdehyde (MDA), lactate dehydrogenase activity and free fatty acids were increased in the kidneys of gestational rats exposed to testosterone. Also, plasma urea and creatinine were elevated. SAc and Eple reversed tested testosterone-induced effects in gestational rats. The exposure to testosterone impairs renal antioxidant defense via AR and MR during late gestation in pregnant rats. The study also provides evidence that sodium acetate protects the kidneys of gestational testosterone-exposed rats against defective antioxidant defense in like manner as MR or AR antagonist.
Assuntos
Acetatos/farmacologia , Antagonistas de Receptores de Andrógenos/farmacologia , Nefropatias , Antagonistas de Receptores de Mineralocorticoides/farmacologia , Receptores Androgênicos/metabolismo , Receptores de Mineralocorticoides/metabolismo , Testosterona/efeitos adversos , Animais , Feminino , Nefropatias/induzido quimicamente , Nefropatias/tratamento farmacológico , Nefropatias/metabolismo , Gravidez , Ratos , Ratos Wistar , Testosterona/farmacologiaRESUMO
High fructose intake has been associated with perturbed lipid, uric acid and lactate homeostasis. However, consumption of fructose-sweetened beverages is not usually regulated during pregnancy. The effect of short-chain fatty acid (acetate) on the metabolic effects of high fructose intake during pregnancy is not known. We hypothesized that acetate prevents gestational fructose-induced hepatic triglyceride (TG) accumulation by suppressing uric acid and lactate production. Pregnant Wistar rats were randomly separated into three groups (n = 6/group) receiving drinking water (CON), 10 % (w/v) fructose drink (FRU) and 10 % (w/v) fructose with 200 mg/kg (w/w; p.o.) sodium acetate (FRU + ACE) daily for nineteen days. Fructose intake resulted in increased body weight gain, liver weight, fluid intake, visceral fat, insulin resistance, fasting blood glucose, insulin, plasma and hepatic TG, total cholesterol, free fatty acid, lipid peroxidation, adenosine deaminase, xanthine oxidase, uric acid, lactate, lactate dehydrogenase, and liver injury marker enzymes. However, gestational high fructose intake led to depressed plasma and hepatic glucose-6-phosphate dehydrogenase (G6PD)-dependent antioxidant barrier, adenosine and food intake. All these effects except water intake and food intake were abated by sodium acetate. These results demonstrate that maternal fructose-enriched drink would cause hepatic TG accumulation that is associated with perturbed glucose, uric acid, lactate homeostasis, and G6PD-dependent antioxidant barrier. These results also demonstrate that acetate protects the liver against gestational fructose-induced TG accumulation by inhibiting uric acid and lactate production. Thus, acetate may be useful in the treatment of hyperuricemia- and hyperlactatemia-related disorders.
Assuntos
Frutose/metabolismo , Resistência à Insulina , Ácido Láctico/metabolismo , Fígado/metabolismo , Acetato de Sódio/farmacologia , Triglicerídeos/metabolismo , Ácido Úrico/metabolismo , Animais , Antioxidantes/metabolismo , Glicemia/análise , Feminino , Teste de Tolerância a Glucose , Ácido Láctico/sangue , Gravidez , Ratos , Ratos Wistar , Triglicerídeos/sangue , Ácido Úrico/sangueRESUMO
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 (ß = 0.307; p = .014) and PAI-1 (ß = 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.