Antioxidant and anti hyperglycemic role of wine grape powder in rats fed with a high fructose diet

BACKGROUND: Metabolic syndrome is a growing worldwide health problem. We evaluated the effects of wine grape powder (WGP), rich in antioxidants and fiber, in a rat model of metabolic syndrome induced by a high fructose diet. We tested whether WGP supplementation may prevent glucose intolerance and decrease oxidative stress in rats fed with a high fructose diet. METHODS: Male Sprague-Dawley rats weighing 180 g were divided into four groups according to their feeding protocols. Rats were fed with control diet (C), control plus 20 % WGP (C + WGP), 50 % high fructose (HF) or 50 % fructose plus 20 % WGP (HF + WGP) for 16 weeks. Blood glucose, insulin and triglycerides, weight, and arterial blood pressure were measured. Homeostasis model assessment (HOMA) index was calculated using insulin and glucose values. A glucose tolerance test was performed 2 days before the end of the experiment. As an index of oxidative stress, thio-barbituric acid reactive substances (TBARS) level was measured in plasma and kidney, and superoxide dismutase was measured in the kidney. RESULTS: Thiobarbituric acid reactive substances in plasma and renal tissue were significantly higher when compared to the control group. In addition, the area under the curve of the glucose tolerance test was higher in HF fed animals. Furthermore, fasting blood glucose, plasma insulin levels, and the HOMA index, were also increased. WGP supplementation prevented these alterations in rats fed with the HF diet. We did not find any significant difference in body weight or systolic blood pressure in any of the groups. CONCLUSIONS: Our results show that WGP supplementation prevented hyperglycemia, insulin resistance and reduced oxidative stress in rats fed with HF diet. We propose that WGP may be used as a supplement in human food as well.

Cyclooxygenase-2 and hypoxia-regulated proteins are modulated by basic fibroblast growth factor in acute renal failure

Acute renal failure (ARF) can be caused by injuries that induce tissue hypoxia, which in turn can trigger adaptive or inflammatory responses. We previously showed the participation of basic fibroblast growth factor (FGF-2) in renal repair. Based on this, the aim of this study was to analyze the effect of FGF-2 signaling pathway manipulation at hypoxia-induced protein levels, as well as in key proteins from the vasoactive systems of the kidney. We injected rat kidneys with FGF-2 recombinant protein (r-FGF) or FGF-2 receptor antisense oligonucleotide (FGFR2-ASO) after bilateral ischemia, and evaluated the presence of iNOS, EPO and HO-1, in representation of hypoxia-induced proteins, as well as COX-2, renin, kallikrein, and B2KR, in representation of the vasoactive systems of the kidney. A reduction in iNOS, HO-1, EPO, renin, kallikrein, B2KR, and in renal damage was observed in animals treated with r-FGF. The opposite effect was found with FGF-2 receptor down-regulation. In contrast, COX-2 protein levels were higher in kidneys treated with r-FGF and lower in those that received FGFR2-ASO, as compared to saline treated kidneys. These results suggest that the protective role of FGF-2 in the pathogenesis of ARF induced by I/R is a complex process, through which a differential regulation of metabolic pathways takes place.

Role of reactive oxygen species in bradykinin-induced proliferation of vascular smooth muscle cells

In addition to the induction of cell proliferation and migration, bradykinin (BK) can increase c-fos mRNA expression, activate ERK 1/2 and generate reactive oxygen species (ROS) in vascular smooth muscle cells (VSMC). It is not known, however, whether BK can induce cellular proliferation and extracellular matrix production via redox-sensitive signaling pathways. We investigated the role(s) of ROS in proliferation, migration and collagen synthesis induced by BK in VSMC derived from Sprague Dawley rat aorta. BK (10 nM) increased VSMC proliferation by 30 % (n=5); this proliferation was inhibited by the antioxidants N-acetylcysteine (20 mM) and a-lipoic acid (LA, 250 mM). In addition, BK induced an increase in cell migration and in collagen levels that were blocked by LA. ROS production induced by BK (n=10) was significantly inhibited by bisindolylmaleimide (4mM) and by PD98059 (40mM). These results suggest that: 1) ROS participate in the mechanism(s) used by bradykinin to induce cellular proliferation; 2) bradykinin induces ROS generation through a pathway that involves the kinases PKC and MEK; and 3) ROS participate in the pathways mediating cell migration and the production of collagen as a response to treatment with bradykinin. To our knowledge, this is the first report describing mechanisms to explain the participation of ROS in the cellular proliferation and extracellular matrix pathway regulated by BK.

Hipertrofia vascular: un mismo mensaje una diferente interpretación / Vascular hypertrophy: the same message but a different interpretation

Las células de la musculatura lisa vascular se caracterizan por cambiar su fenotipo de acuerdo al ambiente en que se encuentren. En un individuo adulto y sano, el fenotipo vascular es contráctil. En estas condiciones, las vías de transducción de señales activadas en respuesta a los estímulos, inducen cambios en la concentración de calcio intracelular y en la fosforilación de proteínas que llevan a la contracción o a la relajación de la célula. En patologías como la aterosclerosis, la hipertensión arterial y en la restenosis post-angioplastia, donde se produce una lesión vascular y el endotelio es removido de la superficie luminal del vaso, los estímulo entran en estrecho contacto con las células de músculo liso vascular. La falta de señales provenientes del endotelio, la alteración de la matriz extracelular, la estimulación por el roce y el contacto directo con agonistas en la sangre, induce la desdiferenciación de las células de músculo liso vascular, a un fenotipo sintético y proliferativo. En estas condiciones se altera la expresión de diversas hormonas y factores de crecimiento que pueden actuar de forma autocrina, activando vías de señalización que en el estado diferenciado de la célula no se activan, induciendo la fosforilación de factores transcripcionales y favoreciendo la duplicación celular. En esta revisión se discutirán algunos de los estímulos presentes en la sangre que favorecen la perpetuación del fenotipo sintético y las vías de señales que ellos activan para inducir la proliferación celular