Oral calcium and vitamin D supplements differentially alter exploratory, anxiety-like behaviors and memory in male rats.

Oral calcium and calcium plus vitamin D supplements are commonly prescribed to several groups of patients, e.g., osteoporosis, fracture, and calcium deficiency. Adequate and steady extracellular calcium levels are essential for neuronal activity, whereas certain forms of calcium supplement (e.g., CaCO3) probably interfere with memory function. However, it was unclear whether a long-term use of ionized calcium (calcium chloride in drinking water ad libitum), vitamin D supplement (oral gavage) or the combination of both affected anxiety and memory, the latter of which was probably dependent on the hippocampal neurogenesis. Here, we aimed to determine the effects of calcium and/or vitamin D supplement on the anxiety- and memory-related behaviors and the expression of doublecortin (DCX), an indirect proxy indicator of hippocampal neurogenesis. Eight-week-old male Wistar rats were divided into 4 groups, i.e., control, calcium chloride-, 400 UI/kg vitamin D3-, and calcium chloride plus vitamin D-treated groups. After 4 weeks of treatment, anxiety-, exploration- and recognition memory-related behaviors were evaluated by elevated pulse-maze (EPM), open field test (OFT), and novel object recognition (NOR), respectively. The hippocampi were investigated for the expression of DCX protein by Western blot analysis. We found that oral calcium supplement increased exploratory behavior as evaluated by OFT and the recognition index in NOR test without any effect on anxiety behavior in EPM. On the other hand, vitamin D supplement was found to reduce anxiety-like behaviors. Significant upregulation of DCX protein expression was observed in the hippocampus of both calcium- and vitamin D-treated rats, suggesting their positive effects on neurogenesis. In conclusion, oral calcium and vitamin D supplements positively affected exploratory, anxiety-like behaviors and/or memory in male rats. Thus, they potentially benefit on mood and memory in osteoporotic patients beyond bone metabolism.

Erythropoietin Administration Promotes Expression of VEGF in Renal Ischemic­Reperfusion Injury in Rat Model.

Background: Acute ischemia-reperfusion (I/R) injury is the most common causes of acute renal failure in daily clinical practice. It has been recognized that endothelial cell dysfunction and microvascular injury as the pathophysiological changes during I/R injury. Protective effects of erythropoietin (EPO) have been demonstrated in various experimental models of I/R induced injury. Therefore, the aim of the present study was to investigate whether EPO administration has renoprotective effect against acute renal failure I/R injury in rats by promotion of endothelial progenitor cells (EPCs) mobilization and neovascularization. Material and Method: Male Sprague-Dawley rats were pretreated with EPO (1,000 IU/kg/day, ip); or the placebo for 3 days before the induction of I/R procedure. On day 4, the bilateral renal occlusion for 30 min operations to produce renal I/R injury or treatment with EPO 30 min before the initiation of I/R were done. At the end of the reperfusion period at day 1 day 2 and day 4, blood and renal tissues were collected to investigate renal function and pathohistological examination. The expression levels of CAV-1 and CD34 were determined for circulating of EPCs in blood, while CD34, CAV-1 and VEGFR-2 were investigated for mobilized EPCs in kidney, using real time PCR. The expression level of VEGF was also examined to indicate the angiogenesis in kidney using real time PCR and western blotting. Results: In the I/R group, the significantly increased values of serum urea and creatinine were found on Day 1 after ischemia, as compared to sham group. The development of tubular epithelial cell necrosis, peritubular capillary congestion and mild interstitial infiltration has been observed in this group. Administration of EPO in I/R rat was significantly improved renal function and significantly less the tubular damage. The treatment with EPO significantly increased in expression levels of CD34 and CAV-1 in blood, and also CAV-1, VEGFR-2 and VEGF in kidney tissue in this group, as compared to the I/R group. Conclusion: These results suggest that treatment with EPO protects the kidney from ischemic acute renal injury via increasing the mobilization and recruitment of EPCs, resulting in the induction of expression of VEGF that might play an important role in the repair response.

Protective effect of alpha tocopherol on contrast-induced nephropathy in rats.

BACKGROUND: Contrast-induced nephropathy (CIN) is a prominent cause of in-hospital acute kidney injury occurring after the administration of intravenous radiocontrast medium. Oxidative stress has been proposed as one of the more important mechanisms in the pathogenesis of CIN. The aim of the present study has been to determine the effect of alpha tocopherol on the reduction of renal damage in a rat model of CIN. METHODS: Male Sprague Dawley rats were subjected into six groups pretreated with alpha-tocopherol (250 or 500 mg/kg/day) or the vehicle tweeen80 for 5 days before the induction of CIN. Renal function and oxidative stress markers; level of malondialdehyde (MDA), total antioxidant capacity (TAC), superoxide dismutase (SOD) activity were determined. Kidney tissues were sectioned for pathohistological examination. RESULTS: In the contrast media (CM) group, an increase in serum urea and creatinine was found. Tubular necrosis and peritubular capillary congestion were demonstrated in this group. Also, an imbalance of oxidative stress markers; an increase in MDA and a decreased SOD activity in kidney were shown. On the contrary, in CIN-induced rats administrated with alpha-tocopherol group, a significant reduction of renal function and renal MDA, together with a significant increase of renal SOD, were observed. Interestingly, a reduction in MDA and an increase of TAC in serum, along with prevention of tubular injury, were demonstrated in this group, as compared to the CM group. CONCLUSION: This present study demonstrated that alpha tocopherol showed protective effect on the rat renal damage induced CIN. Therefore, this vitamin could be used as an antioxidant to attenuate the radiocontrast oxidative damage.

Protective effect of alpha tocopherol on contrast-induced nephropathy in rats

Background: Contrast-induced nephropathy (CIN) is a prominent cause of in-hospital acute kidney injury occurring after the administration of intravenous radiocontrast medium. Oxidative stress has been proposed as one of the more important mechanisms in the pathogenesis of CIN. The aim of the present study has been to determine the effect of alpha tocopherol on the reduction of renal damage in a rat model of CIN. Methods: Male Sprague Dawley rats were subjected into six groups pretreated with alpha-tocopherol (250 or 500mg/kg/day) or the vehicle tweeen 80 for 5 days before the induction of CIN. Renal function and oxidative stress markers; level of malondialdehyde (MDA), total antioxidant capacity (TAC), superoxide dismutase (SOD) activity were determined. Kidney tissues were sectioned for pathohistological examination. Results: In the contrast media (CM) group, an increase in serum urea and creatinine was found. Tubular necrosis and peritubular capillary congestion were demonstrated in this group. Also, an imbalance of oxidative stress markers; an increase in MDA and a decreased SOD activity in kidney were shown. On the contrary, in CIN-induced rats administrated with alpha-tocopherol group, a significant reduction of renal function and renal MDA, together with a significant increase of renal SOD, were observed. Interestingly, a reduction in MDA and an increase of TAC in serum, along with prevention of tubular injury, were demonstrated in this group, as compared to the CM group. Conclusion: This present study demonstrated that alpha tocopherol showed protective effect on the rat renal damage induced CIN. Therefore, this vitamin could be used as an antioxidant to attenuate the radiocontrast oxidative damage (AU)

Antecedentes: La nefropatía inducida por contraste (NIC) constituye una causa importante del fracaso renal agudo en pacientes hospitalizados. Esta tiene lugar tras la administración de un medio de radiocontraste intravenoso. El estrés oxidativo se ha presentado como uno de los mecanismos más importantes de la patogénesis de la NIC. El objetivo de este estudio es determinar el efecto del alfa-tocoferol sobre la reducción del fracaso renal en un modelo de rata de NIC. Métodos: Las ratas Sprague Dawley machos, tratadas previamente con alfa-tocoferol (250 o 500 mg/kg/día) o con tween 80 durante los 5 días anteriores a la inducción de CIN, fueron divididas en 6 grupos. Se determinaron los marcadores de la función renal y del estrés oxidativo, el nivel de malondialdehído (MDA), la capacidad antioxidante total (CAT) y la actividad de la superóxido dismutasa (SOD). Se seccionaron los tejidos de los riñones para el examen histopatológico. Resultados: En el grupo de medio de contraste (MC), se detectó un aumento de la urea sérica y de la creatinina. Asimismo, se demostró la presencia de necrosis tubular y de congestión capilar peritubular en este grupo. También se detectó un desequilibrio de los marcadores de estrés oxidativo, un aumento de MDA y una disminución de la actividad de la SOD en el riñón. Por el contrario, en el grupo de ratas con NIC inducida a las que se les administró alfa-tocoferol, se observó una reducción importante de la función renal y de la MDA renal, junto con un aumento significativo de la SOD renal. Curiosamente, en comparación con el grupo MC, en este grupo se demostró una reducción de MDA y un aumento de la CAT sérica, así como la prevención de la lesión tubular. Conclusión: Este estudio ha demostrado que el alfa-tocoferol posee un efecto protector del daño renal en ratas con NIC inducida. Por lo tanto, esta vitamina podría utilizarse como antioxidante para atenuar el daño oxidativo del radiocontraste (AU)