Toxic stress, health and nutrition among Brazilian children in shelters.

BACKGROUND: Living in a shelter is an adverse experience that generates toxic stress. This situation can cause the dysregulation of the hypothalamic-pituitary-adrenal axis and exert a negative impact on health.The aim of the present study was to determine the association between toxic stress and social, clinical and nutritional characteristics in children at welfare institutions in a city of northeastern of Brazil. METHODS: An analytical, cross-sectional study was conducted with male and female children up to 60 months of age who live in shelters. Hair cortisol was used for the assessment of stress (immunoassay). The anthropometric data collected were height for age, body mass index for age, arm circumference for age, and head circumference for age (expressed in z-scores). We also evaluated food intake using markers proposed by the Brazilian Dietary and Nutritional Vigilance Surveillance System as well as the occurrence of dental caries and anemia. RESULTS: Sixty-three children one to 60 months of age participated in the present study. Asthma was the most frequent disease (11.1%). The prevalence of short stature, anemia and dental caries in the sample was 22.2, 22.2 and 9.4%, respectively. Cortisol levels ranged from 0.93 pg/mg to 391.29 pg/mg (median: 6.17 pg/mg). Higher cortisol levels were found in children with illnesses (p = 0.012) and those who had been hospitalized after being admitted to the institutions (p = 0.001). CONCLUSIONS: The majority of children had unhealthy eating behavior. The cortisol concentrations found in the present study were suggestive of dysregulation of the hypothalamic-pituitary-adrenal axis. Hypercortisolism was associated with illness and hospitalization.

High-dose Nandrolone Decanoate induces oxidative stress and inflammation in retroperitoneal adipose tissue of male rats.

The non-therapeutic use of the androgenic anabolic steroid Nandrolone Decanoate is popular due to its effects on physical performance and body composition, especially for its lipolytic and anabolic effects associated. However, high doses of such drugs are often associated with a series of pathologies related to unbalanced redox homeostasis, which, in turn, can be linked to inflammation. The oxidative stress onset could deregulate the secretion of cytokines, evidencing a dysfunctional adipocyte. Thus, the aim of this study was to investigate the effect of supraphysiological doses of Nandrolone Decanoate on redox homeostasis of retroperitoneal fatpad of male rats and its relationship with cytokines-based inflammatory signaling. Hydrogen peroxide production was assessed in the retroperitoneal fat pad of adult male rats which received either 10 mg kg of Nandrolone Decanoate or only a vehicle. Also, catalase, superoxide dismutase and glutathione peroxidase activities were measured, together with total reduced thiols and protein carbonylation, as well as IL-1ß, TNF-α, and IL-6 local levels. High doses of Nandrolone Decanoate caused an increase in the hydrogen peroxide production, together with lower activities of the antioxidant enzymes and lower levels of total reduced thiol. There were also higher protein carbonylation and greater levels of IL-1ß, TNF-α, and IL-6 in the treated group compared to control group. Therefore, it was possible to verify that high doses of Nandrolone Decanoate cause oxidative stress and induce higher inflammatory signaling in retroperitoneal fat pad of male rats.

Phytomodulatory proteins promote inhibition of hepatic glucose production and favor glycemic control via the AMPK pathway.

Phytomodulatory proteins from the latex of the medicinal plant Calotropis procera has been shown to be implicated in many pharmacological properties. However there is no current information about their activity on glucose metabolism, although the latex is used in folk medicine for treating diabetes. In this study the phytomodulatory proteins (LP) from C. procera latex were assessed on glycemic homeostasis. Control animals received a single intravenous dose (5 mg/kg) of LP or saline solution (CTL). Four hours after treatment, the animals were euthanized and their livers were excised for analysis by western blot and RT-PCR AMP-activated protein kinase (AMPK), phosphoenolpyruvate carboxykinase (PEPCK) and tumor necrosis factor alpha (TNF-α). In vivo tests of intraperitoneal tolerance to insulin, glucose and pyruvate were also performed, and the effect of LP administration on fed glycemia was studied followed by blood analysis to determine serum insulin levels. Treatment with LP reduced glycemia two hours after glucose administration (LP: 87.2 ± 3.70 mg/dL versus CTL: 115.6 ± 8.73 mg/dL). However, there was no change in insulin secretion (CTL: 14.16 ± 0.68 mUI/mL and LP: 14.96 ± 0.55 mUI/mL). LP improved the insulin sensitivity, represented by a superior glucose decay constant during an insulin tolerance test (kITT) (4.17 ± 0.94%/min) compared to the CTL group (0.82 ± 0.72%/min), and also improved glucose tolerance at 30 min (105.2 ± 12.4 mg/dL versus 154.2 ± 18.51 mg/dL), while it decreased hepatic glucose production at 15 and 30 min (LP: 75.5 ± 9.31 and 52.5 ± 12.05 mg/dL compared to the CTL: 79.0 ± 3.02 and 84.5 ± 7.49 mg/dL). Furthermore, there was a significant inhibition of gene expression of PEPCK (LP: 0.66 ± 0.06 UA and CTL: 1.14 ± 0.22 UA) and an increase of phosphorylated AMPK (LP: 1.342 ± 0.21 UA versus CTL: 0.402 ± 0.09 UA). These findings confirm the effect of LP on glycemic control and suggest LP may be useful in diabetes treatment. However, the pharmacological mechanism of LP in PEPCK modulation still needs more clarification.

Sex differences in subcutaneous adipose tissue redox homeostasis and inflammation markers in control and high-fat diet fed rats.

The development of obesity-related metabolic disorders is more evident in male in comparison with female subjects, but the mechanisms are unknown. Several studies have shown that oxidative stress is involved in the pathophysiology of obesity, but the majority of these studies were performed with male animals. The aim of this study was to evaluate the sex-related differences in subcutaneous adipose tissue redox homeostasis and inflammation of rats chronically fed a high-fat diet. NADPH oxidase (NOX), glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase activities were evaluated in the subcutaneous adipose tissue (SC) of adult male and female rats fed either a standard chow (SCD) or a high-fat diet (HFD) for 11 weeks. NOX2 and NOX4 messenger RNA (mRNA) levels, total reduced thiols, interleukin (IL)-1ß, tumor necrosis factor α (TNF-α), and IL-6 were also determined. Higher antioxidant enzyme activities and total reduced thiol levels were detected in SC of control male compared with female rats. Chronic HFD administration increased NOX activity and NOX2 and NOX4 mRNA levels and decreased SOD and GPx activities only in male animals. IL-1ß, TNF-α, and IL-6 levels, as well as Adgre1, CD11b, and CD68 mRNA levels, were also higher in SC of males after HFD feeding. In SC of females, catalase activity was higher after HFD feeding. Taken together, our results show that redox homeostasis and inflammation of SC is sexually dimorphic. Furthermore, males show higher oxidative stress in SC after 11 weeks of HFD feeding owing to both increased reactive oxygen species (ROS) production through NOX2 and NOX4 and decreased ROS detoxification.

n5-STZ Diabetic Model Develops Alterations in Sciatic Nerve and Dorsal Root Ganglia Neurons of Wistar Rats.

One experimental model of diabetes mellitus (DM) similar to type II DM, called n5-STZ, is obtained by a single injection (via i.p.) of streptozotocin (STZ) in the 5th day of life of newborn rats. The present investigation aimed to characterize alterations in excitability of rat peripheral neurons in n5-STZ model. n5-STZ DM was induced, and electrophysiological evaluation was done at 12th week of rat life. Rats developed glucose intolerance, sensory alteration, and hyperglycemia or near-normoglycemia (21.2 ± 1.6 and 7.4 ± 0.4 mmol/L). In near-normoglycemia group the significant electrophysiological alteration observed was decreased in amplitude of 2nd wave (2nd component, conduction velocity: 48.8 m/s) of compound action potential (CAP) of sciatic nerve. For hyperglycemic rats, decreased excitability, amplitude, and conduction velocity of 2nd CAP component of sciatic nerve were found; a depolarization of resting potential (4-5 mV) and reduction in maximum ascendant and descendant inclinations of action potential were found in DRG neurons but no alteration on Na(+) current (INa(+) ). Thus, n5-STZ rats develop alterations in excitability which were related to glycemic levels but were not likely attributable to changes on INa(+) . Our data confirm that n5-STZ model is a useful model to study type II DM.