Efecto de una dieta rica en calcio sobre el metabolismo mineral y óseo en ratas / Effect of a calcium-rich diet on bone and mineral metabolism in rats

Objetivo: Una dieta rica en calcio se ha recomendado generalmente para mantener una adecuada salud ósea; no obstante, estudios recientes han despertado la controversia sobre sus beneficios. En este sentido, la mayoría de los estudios existentes en modelos animales están realizados con dietas deficientes en vitamina D. En este estudio se evaluará el efecto de una dieta rica en calcio sobre el metabolismo mineral y la histomorfometría ósea en rata. Además, en células UMR-106 se evaluó el efecto directo del suplemento de calcio sobre la expresión de genes osteogénicos.Material y métodos: Un grupo de ratas wistar macho de aproximadamente 3 meses de edad fue alimentado con dieta de contenido normal de calcio (0,6%) mientras que otro grupo se alimentó con dieta de alto contenido en calcio (1,2%). Transcurridos 20 días se recogieron muestras de orina 24h, sangre para análisis bioquímicos y el fémur para estudio de histomorfometría ósea. In vitro, se estudió la expresión génica de Runx2, Osterix y Osteocalcina en células UMR-106 cultivadas en condiciones de alto contenido en calcio.Resultados: La ingesta de una dieta rica en calcio redujo la concentración de PTH y calcitriol en plasma, aumentó la calciuria y disminuyó la fosfaturia. A nivel óseo, se observó una drástica disminución de la actividad osteoblástica consistente con la bajada de PTH; sin embargo, el volumen trabecular permaneció similar en ambos grupos. In vitro, el suplemento de calcio no disminuyó la expresión de marcadores osteoblásticos en UMR-106, indicando que los efectos in vivo son mayormente indirectos y debidos a la bajada de PTH.Conclusiones: Una dieta de alto contenido en calcio reduce la concentración de PTH y calcitriol en plasma, resultando en una disminución de la actividad osteoblástica. (AU)

Magnesium: An old player revisited in the context of CKD-MBD.

Chronic kidney disease (CKD) is associated with a wide number of abnormalities in mineral metabolism. Often, these alterations are the leading players in the development of comorbidities associated with CKD, which are risk factors of mortality. In this context, mineral and bone disorder associated with CKD (CKD-MBD) are highlighted, connecting bone, renal, and cardiovascular disorders. Many studies have been led to propose strategies to avoid, reduce, or slow down CKD-MBD progression using different compositions of metallic elements-based P binders such as aluminum, magnesium, or calcium. Magnesium, the aim of this review, has been used by nephrologists to treat CKD-MBD with a variable acceptation due mainly to different results on bone homeostasis. Nowadays, we have new evidence about the efficacy of magnesium supplementation on vascular calcification, renal function, and bone disorders, suggesting potential beneficial effects of Magnesium in the management of CKD-MBD.

Vitamin E protection of obesity-enhanced vascular calcification in uremic rats.

This study aimed to determine the extent of extraskeletal calcification in uremic Zucker rats, by comparing obese and lean phenotypes, and to evaluate the influence of vitamin E (VitE) on the development of calcifications in both uremic rats and human vascular smooth muscle cells (HVSMCs) cultured in vitro. Zucker rats of lean and obese phenotypes with normal renal function [control (C); C-lean and C-obese groups] and with uremia [5/6 nephrectomy (Nx); Nx-lean and Nx-obese groups] and uremic rats treated with VitE (Nx-lean + VitE and Nx-obese + VitE groups) were studied. Uremic groups were subjected to Nx, fed a 0.9% phosphorus diet, and treated with calcitriol (80 ng/kg ip). The aortic calcium concentration was significantly higher (P < 0.05) in Nx-obese rats (10.0 ± 2.1 mg/g tissue) than in Nx-lean rats (3.6 ± 1.3 mg/g tissue). A decrease in plasma glutathione peroxidase activity was observed in Nx-obese rats compared with Nx-lean rats (217.2 ± 18.2 vs. 382.3 ± 15.5 nmol·min(-1)·ml(-1), P < 0.05). Treatment with VitE restored glutathione peroxidase activity and reduced the aortic calcium concentration to 4.6 ± 1.3 mg/g tissue. The differences in mineral deposition between Nx-lean, Nx-obese, Nx-lean + VitE, and Nx-obese + VitE rats were also evidenced in other soft tissues. In HVSMCs incubated with high phosphate, VitE also prevented oxidative stress and reduced calcium content, bone alkaline phosphatase, and gene expression of core-binding factor-α1. In conclusion, uremic obese rats develop more severe calcifications than uremic lean rats and VitE reduces oxidative stress and vascular calcifications in both rats and cultures of HVSMCs.

Mecanismos de lesión hepatocelular / Mechanisms of liver cell injury

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Effect of catecholestrogen administration during adriamycin-induced cardiomyopathy in ovariectomized rat.

The therapeutical beneficial effect of estrogen-derived metabolites or catecholestrogens is controversial. These molecules are produced during estrogen therapy based on 17-beta-estradiol treatment. The metabolization of 17-beta-estradiol is carried out in brain, kidney or liver, and triggers different products such as 2- and 4- hydroxyestradiol (2OH and 4OH). These products have shown antioxidant properties against oxidative stress (OS) in several experimental models. Different noxious side effects related to those metabolites have also been observed upon estrogen therapy. In this sense, catecholestrogens seem to be implicated in tumoral and mutagenic process after long treatment with estrogens substitutive therapy. In our study, we have verified that 2OH and 4OH have antioxidant and cardioprotective effects against adriamycin (AD)-induced cardiomyopathy in ovariectomized (OVX) rats. Catecholestrogens diminished the lipid peroxides and carbonyl protein (CO) content, and different enzymes related to cell injury (creatinine kinase, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase) in cardiac tissue from OVX-, AD-, and OVX+AD-treated rats. All these changes were correlated to a recovery on reduced glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) in heart tissue. The present study showed that 2OH and 4OH reduced all the parameters related to OS, antioxidant depletion and cardiac injury in OVX rats treated or not with AD.

Effect of red wine on oxidative stress and hypercholesterolemia induced by feeding a high-cholesterol diet in rat.

The effect of red wine on oxidative stress and hypercholesterolemia induced by feeding a high-cholesterol diet (supplemented with 1.65% of cholesterol (w/w) for 4 weeks) to female Wistar rats was examined. When red wine was simultaneously supplemented to high-cholesterol diet, total cholesterol, triglycerides, atherogenic index and lipid peroxidation products significantly decreased compared with the high-cholesterol diet alone, while GSH content and antioxidative enzymes activities were enhanced. In the hypercholesterolemic rat the excretion of fecal bile acids, as well as their plasma and hepatic concentrations were increased significantly. Administration of red wine enhanced these values, indicating an increase in the cholesterol degradation. These results suggest that red wine may have a protective effect against oxidative stress, hypercholesterolemia and atherogenic index induced by high-cholesterol diet.

Effect of melatonin on the oxidative stress in N1E-115 cells is not mediated by mt1 receptors.

To explore if protective effect of melatonin on oxidative stress induced by okadaic acid, an inhibitor of protein phosphatases PP1 and PP2A, is mediated by membrane receptors subtype mt1, we used an in vitro model with N1E-115 neuroblastoma cells. We demonstrated that exposure of cells to 50 nM okadaic acid for 2 h induces a reduction in the activity of antioxidative enzymes, and an increase of lipid peroxidation products, while melatonin prevents the effect of okadaic acid. On the other hand, the presence of luzindole, 20 min before adding melatonin, did not cause changes on the effect of the melatonin on oxidative stress. These results seem to indicate that protective effect of melatonin is not mediated by mt1 receptors.