María S. Gimenez

Temporal patterns of lipoperoxidation and antioxidant enzymes are modified in the hippocampus of vitamin A-deficient rats.

Animals can adapt their behavior to predictable temporal fluctuations in the environment through both, memory‐and‐learning processes and an endogenous time‐keeping mechanism. Hippocampus plays a key role in memory and learning and is especially susceptible to oxidative stress. In compensation, antioxidant enzymes activity, such as Catalase (CAT) and Glutathione peroxidase (GPx), has been detected in this brain region. Daily rhythms of antioxidant enzymes activity, as well as of glutathione and lipid peroxides levels, have been described in brain. Here, we investigate day/night variations in lipoperoxidation, CAT, and GPx expression and activity, as well as the temporal fluctuations of two key components of the endogenous clock, BMAL1 and PER1, in the rat hippocampus and evaluate to which extent vitamin A deficiency may affect their amplitude or phase. Holtzman male rats from control, vitamin A‐deficient, and vitamin A‐refed groups were sacrificed throughout a 24‐h period. Daily levels of clock proteins, lipoperoxidation, CAT and GPx mRNA, protein, and activity, were determined in the rat hippocampus obtained every 4 or 5 h. Gene expression of RARα and RXRβ was also quantified in the hippocampus of the three groups of rats. Our results show significant daily variations of BMAL1 and PER1 protein expression. Rhythmic lipoperoxidation, CAT, and GPx, expression and activity, were also observed in the rat hippocampus. Vitamin A deficiency reduced RXRβ mRNA level, as well as the amplitude of BMAL1 and PER1 daily oscillation, phase‐shifted the daily peak of lipoperoxidation, and had a differential effect on the oscillating CAT and GPx mRNA, protein, and activity. Learning how vitamin A deficiency affects the circadian gene expression in the hippocampus may have an impact on the neurobiology, nutritional and chronobiology fields, emphasizing for the first time the importance of nutritional factors, such as dietary micronutrients, in the regulation of circadian parameters in this brain memory‐and‐learning‐related region.

Protective effect of soybeans as protein source in the diet against cadmium-aorta redox and morphological alteration

We investigated the effects of cadmium exposition on thoracic aorta redox status and morphology, and the putative protective effect of soybeans in the diet. Male Wistar rats were separated into 6 groups: 3 fed with a diet containing casein and 3 containing soybeans, as protein source. Within each protein group, one was given tap water (control) and the other two tap water containing 15 and 100 ppm of Cd(2+), respectively, for two months. In rats fed with casein diet, 15 ppm of Cd induced an increase of thiobarbituric acid-reactive substances (TBARS), and of the catalase (CAT) and glutathione peroxidase (GPx) activities, which were even higher with 100 ppm of Cd(2+), in aorta. Also, 100 ppm Cd(2+) exposure increased superoxide dismutase (CuZnSOD) activity; CAT, GPX, SOD, Nrf2 and metallothioneine II mRNA expressions and CAT, GPx and NOX-2 protein levels, compared with control. Aorta endothelial and cytoplasmic alterations were observed. However, with the soybeans diet, 15 and 100 ppm of Cd(2+) did not modify TBARS levels; CAT, GPX and Nrf2 mRNA expressions; CAT, GPx and NOX-2 protein; and the aorta morphology, compared with control. The soybean diet attenuates the redox changes and protects against morphological alterations induced, in a dose-dependent way, by Cd in aorta.

Vitamin A deficiency injures liver parenchyma and alters the expression of hepatic extracellular matrix

Vitamin A is an essential lipid‐soluble nutrient that is crucial for morphogenesis and adult tissue maintenance. The retinoid homeostasis in the liver depends on a regular supply of vitamin A from an adequate dietary intake to preserve the normal organ structure and functions. This study focuses on the effect of vitamin A deficiency on the morphology and extracellular proteins expression of the liver in adult Wistar rats. Animals were fed with a normal (control group) or deficient vitamin A diet for 3 months. At the end of the experimental period, histological examination of the livers under light and electron microscopy revealed that vitamin A deficiency produced a loss of hepatocyte cord disposition with an irregular parenchymal organization. Abundant fat droplets were present in the cytoplasm of the hepatocytes. Elongated myofibroblastic‐like cells with an irregular cytoplasmic process and without lipid droplets could be seen at the perisinusoidal space, where an elevated intensity of alpha smooth muscle actin (α‐SMA) was observed. These results suggest that an activation of hepatic stellate cells (HSCs) occurred. Moreover, immunochemical methods revealed that vitamin A deficiency led to an increased expression of hepatic fibronectin, laminin and collagen type IV. We propose that vitamin A deprivation caused liver injury and that HSCs underwent a process of activation in which they produced α‐SMA and synthesized extracellular components. These changes may be a factor predisposing to liver fibrosis. In consequence, vitamin A deprivation could affect human and animal health. Copyright

Cytoprotective mechanisms in rats lung parenchyma with zinc deprivation

Abstract Suboptimal intake of Zinc (Zn) is one of the most common worldwide nutritional problems. The aim of this study is to provide new evidence on the relation between moderate Zn restriction, and cytoprotective functions in airway epithelium. We analyzed the effect of moderate Zn deficiency (ZD) on the expression of several pro and anti-apoptotic proteins and cytoprotective factors (Hsp27 and Hsp 70i), as well as the effect of restoring Zn during the refeeding period. Adult male rats were divided into three groups: Zn-adequate control group, Zn-deficient group and Zn-refed group. Our previous findings showed an important oxidative and nitrosative stress during ZD, this situation is accompanied by inflammation and alterations in the expression of matrix extracellular proteins. We observed a strong immunopositive area of anti and pro-apoptotics proteins in ZD groups. The mRNA levels of Nrf-2, Bax and Bad were increased in ZD, while in ZD refed group its levels were similar to the control values. The increased expression of Nrf-2 is likely to be critical for protection of lung under inflammatory process triggered during ZD. Hsp27 and Hsp 70i showed an increase of immunostaining area but they were not significant. During the supplementation period, heat-shock proteins increased significantly. In conclusion, our results provide further evidence of the pathways involved in cytoprotection and apoptosis caused by ZD. Additional studies are required in order to investigate whether Hsp27 and Hsp70 are consistently associated with cellular stress and inflammation in lung. There may be a beneficial role for improved Zn nutrition or Zn supplements early in lung pathology.

Alterations of the extracellular matrix of lung during zinc deficiency.

Suboptimal intake of Zn is one of the most common nutritional problems worldwide. Previously, we have shown that Zn deficiency (ZD) produces oxidative and nitrosative stress in the lung of rats. We analyse the effect of moderate ZD on the expression of several intermediate filaments of the cytoskeleton, as well as the effect of restoring Zn during the refeeding period. Adult male rats were divided into three groups: Zn-adequate control (CO) group; ZD group; Zn-refeeding group. CerbB-2 and proliferating cell nuclear antigen (PCNA) expression was increased in the ZD group while the other parameters did not change. During the refeeding time, CerbB-2, cytokeratins, vimentin and PCNA immunostaining was higher than that in the CO group. The present findings indicate that the overexpression of some markers could lead to the fibrotic process in the lung. Perhaps ZD implications must be taken into account in health interventions because an inflammation environment is associated with ZD in the lung.

Nutrition and Central Nervous System

Clinical studies have revealed that depression is accompanied by impaired brain function and cognitive performances or neurodegenerative processes. Moreover, accumulation of oxidative damage has been implicated in aging and various neurological disorders. This chapter aims to integrate the current knowledge on the relation between brain and diverse alterations in nutrition. The mammalian brain is a lipid-rich organ, where lipids content in gray matter is 36–40% lipid. However, the regulation of cholesterol transport from astrocytes to neurons still remains unclear, among other things. In addition to that, micronutrient status can affect cognitive function at all ages. Vitamin deficiency could influence memory function, and might contribute to cognitive impairment and dementia.

Dietary soy protein improves adipose tissue dysfunction by modulating parameters related with oxidative stress in dyslipidemic insulin-resistant rats

The present study investigates the benefits of the dietary intake of soy protein on adipose tissue dysfunction in a rat model that mimics several aspects of the human metabolic syndrome. Wistar rats were fed a sucrose-rich diet (SRD) for 4 months. After that, half of the animals continued with SRD until month 8 while in the other half, casein protein was replaced by isolated soy protein for 4 months (SRD-S). A reference group consumed a control diet all the time. In adipose tissue we determined: i) the activities of antioxidant enzymes, gene expression of Mn-superoxide dismutase (SOD) and glutathione peroxidase (GPx), and glutathione redox state ii) the activity of xanthine oxidase (XO), ROS levels and the gene expression of NAD(P)H oxidase iii) the expression of the nuclear factor erythroid-2 related factor-2 (Nrf2). Besides, adiposity visceral index, insulin sensitivity, and tumor necrosis factor-α (TNF-α) in plasma were determined. Compared with the SRD-fed rats, the animals fed a SRD-S showed: activity normalization of SOD and glutathione reductase, improvement of mRNA SOD and normalization of mRNA GPx without changes in the expression of the Nrf2, and improvement of glutathione redox state. These results were accompanied by a normalization of XO activity and improvement of both the ROS production as well as TNF-α levels in plasma. Besides, adipocyte size distribution, adiposity visceral index and insulin sensitivity improved. The results suggest that soy protein can be a complementary nutrient for treating some signs of the metabolic syndrome.