Paraprobiotics and Postbiotics-Current State of Scientific Research and Future Trends toward the Development of Functional Foods.

The potential of paraprobiotics and postbiotics to be used as beneficial agents for human health has caused an effort by the scientific community to gather information about the bioactivity of these compounds and production methods. Understanding the evolution of scientific research in this area of study is important to understand the future perspectives and the main bottlenecks of scientific and technological development involving these compounds. In this scenario, this review work used a bibliometric analysis tool intending to improve the scientific documentation, bringing information and communicating the results to the scientific community through the quantitative analysis of the current literature, available in one of the main databases, the Web of Science, also providing recent information on the evolution and future perspectives in the field of paraprobiotic and postbiotic development. The results of this study showed that the main studies discuss the bioactivity of these compounds. Concerning the development of functional foods, there is a need for extensive research on production methods and the interaction of these compounds with food. However, it concluded that much still needs to be studied to prove the claims of bioactivity, especially when used for the development of functional foods.

Transformation of Residual Açai Fruit (Euterpe oleracea) Seeds into Porous Adsorbent for Efficient Removal of 2,4-Dichlorophenoxyacetic Acid Herbicide from Waters.

Brazil's production and consumption of açai pulp (Euterpe oleracea) occur on a large scale. Most of the fruit is formed by the pit, which generates countless tons of residual biomass. A new purpose for this biomass, making its consumption highly sustainable, was presented in this study, where activated carbon (AC) was produced with zinc chloride for later use as an adsorbent. AC carbon formed by carbon and with a yield of 28 % was satisfactorily used as an adsorbent in removing the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D). Removal efficiency was due to the highly porous surface (Vp = 0.467 cm3 g-1; Dp = 1.126 nm) and good surface área (SBET = 920.56 m2 g-1). The equilibrium data fit the Sips heterogeneous and homogeneous surface model better. It was observed that the increase in temperature favored adsorption, reaching a maximum experimental capacity of 218 mg g-1 at 328 K. The thermodynamic behavior indicated a spontaneous, favorable, and endothermic behavior. The magnitude of the enthalpy of adsorption was in agreement with the physical adsorption. Regardless of the herbicide concentration, the adsorbent displayed fast kinetics, reaching equilibrium within 120 min. The linear driving force (LDF) model provided a strong statistical match to the kinetic curves. AC with zinc chloride (ZnCl2), created from leftover açai biomass, is a potential alternative as an adsorbent for treating effluents containing 2,4-D.

Highly Efficient Adsorption of Tetracycline Using Chitosan-Based Magnetic Adsorbent.

Herein, tetracycline adsorption employing magnetic chitosan (CS·Fe3O4) as the adsorbent is reported. The magnetic adsorbent was synthesized by the co-precipitation method and characterized through FTIR, XRD, SEM, and VSM analyses. The experimental data showed that the highest maximum adsorption capacity was reached at pH 7.0 (211.21 mg g-1). The efficiency of the magnetic adsorbent in tetracycline removal was dependent on the pH, initial concentration of adsorbate, and the adsorbent dosage. Additionally, the ionic strength showed a significant effect on the process. The equilibrium and kinetics studies demonstrate that Sips and Elovich models showed the best adjustment for experimental data, suggesting that the adsorption occurs in a heterogeneous surface and predominantly by chemical mechanisms. The experimental results suggest that tetracycline adsorption is mainly governed by the hydrogen bonds and cation-π interactions due to its pH dependence as well as the enhancement in the removal efficiency with the magnetite incorporation on the chitosan surface, respectively. Thermodynamic parameters indicate a spontaneous and exothermic process. Finally, magnetic chitosan proves to be efficient in TC removal even after several adsorption/desorption cycles.

Incidence of lung cancer and mortality among civil construction industry workers: A protocol for a systematic review and meta-analysis.

BACKGROUND: The construction sector is one of the most stable growth industries in the world. However, many studies have suggested an association between occupational exposure in civil construction and lung cancer risk. Thus, this study aims to assess lung cancer risk in civil construction workers occupationally exposed to physical and chemical agents through a systematic review and meta-analysis. METHODS/DESIGN: Studies will be identified by searching PUBMED, Embase, SCOPUS, WEB OF SCIENCE and the reference list of included articles. Eligible study designs will be cohort, cross-sectional, and case-control studies that report occupational exposure to physical or chemical agents and lung cancer risk through mortality or incidence outcomes. A meta-analysis will be used to combine odds ratios (ORs) from case-control studies and relative risks (RR) from cohort studies. Two reviewers will independently screen articles, extract data, and assess scientific quality using standardized forms and ROBINS-E tool if available. Otherwise, the New-Castle Ottawa rating scale will be used. Any of those will also be used in combination with the GRADE approach for quality of evidence. Overall risk estimates and their corresponding 95% confidence intervals (CIs) will be obtained using the random-effects model meta-analysis. This systematic review and meta-analysis will be conducted following the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. Results will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. DISCUSSION: This review will identify and synthesize studies investigating the association between occupational exposure in the construction industry and lung cancer. The findings will help governmental entities and researchers with evidence-based decision-making because they will integrate and validate the evidence on construction workers' health effects due to occupational exposure. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020164209.

Hepatic and neurobiological effects of foetal and breastfeeding and adulthood exposure to methylmercury in Wistar rats.

Methylmercury (MeHg) is an organic bioaccumulated mercury derivative that strongly affects the environment and represents a public health problem primarily to riparian communities in South America. Our objective was to investigate the hepatic and neurological effects of MeHg exposure during the phases foetal and breast-feeding and adult in Wistar rats. Wistar rats (n = 10) were divided into 3 groups. Control group received mineral oil; The simple exposure (SE) group was exposed only in adulthood (0.5 mg/kg/day); and double exposure (DE) was pre-exposed to MeHg 0.5 mg/kg/day during pregnancy and breastfeeding (±40 days) and re-exposed to MeHg for 45 days from day 100. After, we evaluated possible abnormalities. Behavioral and biochemical parameters in liver and occipital cortex (CO), markers of liver injury, redox and AKT/GSK3ß/mTOR signaling pathway. Our results showed that both groups treated with MeHg presented significant alterations, such as decreased locomotion and exploration and impaired visuospatial perception. The rats exposed to MeHg showed severe liver damage and increased hepatic glycogen concentration. The MeHg groups showed significant impairment in redox balance and oxidative damage to liver macromolecules and CO. MeHg upregulated the AKT/GSK3ß/mTOR pathway and the phosphorylated form of the Tau protein. In addition, we found a reduction in NeuN and GFAP immunocontent. These results represent the first approach to the hepatotoxic and neural effects of foetal and adult MeHg exposure.

Guarana supplementation attenuated obesity, insulin resistance, and adipokines dysregulation induced by a standardized human Western diet via brown adipose tissue activation.

Obesity is a metabolic disorder associated with adverse health consequences that has increased worldwide at an epidemic rate. This has encouraged many people to utilize nonprescription herbal supplements for weight loss without knowledge of their safety or efficacy. However, mounting evidence has shown that some herbal supplements used for weight loss are associated with adverse effects. Guarana seed powder is a popular nonprescription dietary herb supplement marketed for weight loss, but no study has demonstrated its efficacy or safety when administered alone. Wistar rats were fed four different diets (low-fat diet and Western diet with or without guarana supplementation) for 18 weeks. Metabolic parameters, gut microbiota changes, and toxicity were then characterized. Guarana seed powder supplementation prevented weight gain, insulin resistance, and adipokine dysregulation induced by Western diet compared with the control diet. Guarana induced brown adipose tissue expansion, mitochondrial biogenesis, uncoupling protein-1 overexpression, AMPK activation, and minor changes in gut microbiota. Molecular docking suggested a direct activation of AMPK by four guarana compounds tested here. We propose that brown adipose tissue activation is one of the action mechanisms involved in guarana supplementation-induced weight loss and that direct AMPK activation may underlie this mechanism. In summary, guarana is an attractive potential therapeutic agent to treat obesity.

The effects of retinol oral supplementation in 6-hydroxydopamine dopaminergic denervation model in Wistar rats.

Vitamin A (retinol) is involved in signaling pathways regulating gene expression and was postulated to be a major antioxidant and anti-inflammatory compound of the diet. Parkinson's disease (PD) is a progressive neurodegenerative disorder, characterized by loss of nigral dopaminergic neurons, involving oxidative stress and pro-inflammatory activation. The aim of the present study was to evaluate the neuroprotective effects of retinol oral supplementation against 6-hydroxydopamine (6-OHDA, 12 µg per rat) nigrostriatal dopaminergic denervation in Wistar rats. Animals supplemented with retinol (retinyl palmitate, 3000 IU/kg/day) during 28 days exhibited increased retinol content in liver, although circulating retinol levels (serum) were unaltered. Retinol supplementation did not protect against the loss of dopaminergic neurons (assessed through tyrosine hydroxylase immunofluorescence and Western blot). Retinol supplementation prevented the effect of 6-OHDA on Iba-1 levels but had no effect on 6-OHDA-induced GFAP increase. Moreover, GFAP levels were increased by retinol supplementation alone. Rats pre-treated with retinol did not present oxidative damage or thiol redox modifications in liver, and the circulating levels of TNF-α, IL-1ß, IL-6 and IL-10 were unaltered by retinol supplementation, demonstrating that the protocol used here did not cause systemic toxicity to animals. Our results indicate that oral retinol supplementation is not able to protect against 6-OHDA-induced dopaminergic denervation, and it may actually stimulate astrocyte reactivity without altering parameters of systemic toxicity.

Supplementation with Achyrocline satureioides Inflorescence Extracts to Pregnant and Breastfeeding Rats Induces Tissue-Specific Changes in Enzymatic Activity and Lower Neonatal Survival.

Achyrocline satureioides (AS, family Asteraceae) is a plant widely used in traditional medicine for stomach, digestive, and gastrointestinal disorders during pregnancy. Studies regarding the indiscriminate use of plant infusions during pregnancy are limited. Recent reports have shown that chronic flavonoid supplementation induces toxicity in vivo and raises the mortality rates of healthy subjects. Therefore, we investigated whether supplementation of pregnant and lactating Wistar rats with two AS inflorescence extracts, consisting of an aqueous (AQ) extract similar to a tea (47 mg·kg-1·day) and a hydroethanolic (HA) extract (35 mg·kg-1·day-1) with a higher flavonoid content, could induce redox-related side effects. Total reactive antioxidant potential (TRAP), thiobarbituric reactive species (TBARS), and total reduced thiol (SH) content were evaluated. Superoxide dismutase (SOD) and catalase (CAT) activities were additionally quantified. Our data suggest that both AQ and HA of AS inflorescence extracts may induce symptoms of toxicity in concentrations of (47 mg·kg-1·day) and (35 mg·kg-1·day-1), respectively, in mothers regarding the delivery index and further decrease of neonatal survival. Of note, significant tissue-specific changes in maternal (liver, kidney, heart, and hippocampus) and pups (liver and kidney) biochemical oxidative parameters were observed. Our findings provide evidence that may support the need to control supplementation with the AQ of AS inflorescence extracts during gestation due to potential toxicity in vivo, which might be related, at least in part, to changes in tissue-specific redox homeostasis and enzymatic activity.

Curcumin Supplementation Decreases Intestinal Adiposity Accumulation, Serum Cholesterol Alterations, and Oxidative Stress in Ovariectomized Rats.

The aim of this study was to investigate the potential of curcumin oral supplementation (50 and 100 mg/Kg/day, for 30 days) in circumventing menopause-associated oxidative stress and lipid profile dysfunctions in a rat ovariectomy (OVX) model. Female Wistar rats were operated and randomly divided into either sham-operated or OVX groups. Sham-operated group (n = 8) and one OVX group (n = 11) were treated with vehicle (refined olive oil), and the other two OVX groups received curcumin at 50 or 100 mg/Kg/day doses (n = 8/group). OVX vehicle-treated animals presented a higher deposition of intestinal adipose tissue as well as increased serum levels of IL-6, LDL, and total cholesterol when compared to sham-operated rats. In addition, several oxidative stress markers in serum, blood, and liver (such as TBARS, carbonyl, reduced-sulphydryl, and nonenzymatic antioxidant defenses) were altered toward a prooxidant status by OVX. Interestingly, curcumin supplementation attenuated most of these parameters to sham comparable values. Thus, the herein presented results show that curcumin may be useful to ameliorate lipid metabolism alterations and oxidative damage associated with hormone deprivation in menopause.

In Vitro Neuroprotective Effect of Shikimic Acid Against Hydrogen Peroxide-Induced Oxidative Stress.

Shikimic acid (SA), originally extracted from Illicium verum Hook. fil., is an indispensable starting material for the synthesis of the antiviral drug Oseltamivir (Tamiflu(®)) with very limited number of studies regarding its biological effects in vitro. Therefore, we here evaluated the thermoanalytical profile, redox properties, and in vitro effects of SA on human neuronal-like cells (SH-SY5Y). The thermoanalytical profile of SA was studied by using differential scanning calorimetry (DSC) and thermogravimetry/derivative thermogravimetry (TG/DTG) characterization. Both antioxidant potential and in vitro lipoperoxidation levels were analyzed. Cell viability and intracellular reactive species (RS) production was determined by DCF and SRB assays, respectively. Our results show in vitro antioxidant activity of SA without exerting cytotoxic effects on SH-SY5Y cells at tested concentrations of 10 nM, 10 µM, and 10 mM. In addition, SA protected the cells against H2O2-induced toxicity; effect that could be related, at least in part, with decreased intracellular RS production and its antioxidant potential. The present study shows evidence for neuroprotective actions of SA against oxidative stress-induced toxicity on SH-SY5Y cells, inviting for further investigation about its potential use in the context of oxidative stress-associated neurodegenerative diseases.

Chronic retinyl palmitate supplementation to middle-aged Wistar rats disrupts the brain redox homeostasis and induces changes in emotional behavior.

SCOPE: Aging process makes older adults especially vulnerable to neurodegeneration and mental disorders. Overconsumption-related neurotoxic effects of certain dietary nutrients by older population could represent a contribution factor for the development of neuropsychiatric conditions by this subpopulation. Thus, we here investigated whether chronic supplementation with retinyl palmitate, at doses commonly found in vitamin supplements (300, 600, and 3000 mcg of RAE/kg/day), could have an impact on emotional behavior of middle-aged Wistar rats. METHODS AND RESULTS: We report that supplementation with retinyl palmitate for 28 days induces an altered emotional state of middle-aged Wistar rats and oxidative stress in cerebellum, cerebral cortex, hippocampus, and striatum, associated with imbalance of enzymatic antioxidant defenses, decrease in non-enzymatic antioxidant defenses, and increase in protein and lipid damages. CONCLUSION: Our data show evidence for (i) changes in emotional reactivity, similar to anxiety, in middle-aged rats chronically supplemented with retinyl palmitate; and (ii) suggest a possible interrelation between pro-oxidant events in the brain and these differences in the behavioral profile that cannot be attributed to hepatotoxicity. Our results invite for additional studies to further investigate such interrelation.

Supplementation of adult rats with moderate amounts of ß-carotene modulates the redox status in plasma without exerting pro-oxidant effects in the brain: a safer alternative to food fortification with vitamin A?

Despite the antioxidant potential of vitamin A, recent studies reported that chronic retinol ester supplementation can also exert pro-oxidant effects and neurotoxicity in vivo and raises the mortality rates among healthy subjects. Our aim was to find evidence for a safer (i.e., less toxic) molecule with provitamin A activity. Therefore, we investigated whether chronic supplementation of healthy Wistar rats with ß-carotene (0.6, 3, and 6 mg/kg/day) would demonstrate antioxidant characteristics without leading to pro-oxidant side effects in the brain. Total reactive antioxidant potential (TRAP), thiobarbituric reactive species level (TBARS), and total reduced thiol content (SH) were evaluated in plasma. TBARS and SH were additionally evaluated in selected brain regions together with superoxide dismutase (SOD) and catalase (CAT) activity. In the present study, we show that ß-carotene is able to exert antioxidant activity in plasma without triggering pro-oxidant events in the brain, providing evidence that may justify its further evaluation as a safer nutritional supplement with provitamin A activity.

Guarana (Paullinia cupana Mart.) prevents ß-amyloid aggregation, generation of advanced glycation-end products (AGEs), and acrolein-induced cytotoxicity on human neuronal-like cells.

Advanced glycation end-products (AGEs) are considered potent molecules capable of promoting neuronal cell death and participating in the development of neurodegenerative disorders such as Alzheimer's disease (AD). Previous studies have shown that AGEs exacerbate ß-amyloid (Aß) aggregation and AGE-related cross-links are also detected in senile plaques. Acrolein (ACR) is an α, ß-unsaturated aldehyde found in the environment and thermally processed foods, which can additionally be generated through endogenous metabolism. The role of ACR in AD is widely accepted in the literature. Guarana (Paullinia cupana Mart.) is popularly consumed by the population in Brazil, mainly for its stimulant activity. In the present study, we showed that guarana (10, 100, and 1000 µg/mL) is able to prevent protein glycation, ß-amyloid aggregation, in vitro methylglyoxal, glyoxal, and ACR (20 µM)-induced toxicity on neuronal-like cells (SH-SY5Y). Since these are considered typical AD pathological hallmarks, we propose that guarana may deserve further research as a potential therapeutic agent in such a neurodegenerative disease.

The association effect of insulin and clonazepam on oxidative stress in liver of an experimental animal model of diabetes and depression.

CONTEXT: It is known that oxidative stress occurs in peripheral blood in an experimental animal model of diabetes and depression, and acute treatment with insulin and clonazepam (CNZ) has a protective effect on oxidative stress in this model. OBJECTIVE: This study evaluated the effect of insulin plus CNZ on oxidative stress parameters in the liver of diabetic male rats induced with streptozotocin (STZ) and subjected to forced swimming test (FST). MATERIALS AND METHODS: Diabetes was induced by a single intraperitoneal (i.p.) dose of STZ 60 mg/kg in male Wistar rats. Insulin (4 IU/kg) plus CNZ acute i.p. treatment (0.25 mg/kg) was administered 24, 5 and 1 h before the FST. Nondiabetic control rats received i.p. injections of saline (1 mL/kg). Protein oxidative damage was evaluated by carbonyl formation and the antioxidant redox parameters were analyzed by the measurements of enzymatic activities of the superoxide dismutase (SOD), catalase and glyoxalase I (GLO). Glycemia levels also were determined. RESULTS: Our present study has shown an increase in carbonyl content from diabetic rats subjected to FST (2.04 ± 0.55), while the activity of catalase (51.83 ± 19.02) and SOD (2.30 ± 1.23) were significantly decreased in liver from these animals, which were reverted by the treatment. Also, the activity of GLO (0.15 ± 0.02) in the liver of the animals was decreased. DISCUSSION AND CONCLUSION: Our findings showed that insulin plus CNZ acute treatment ameliorate the antioxidant redox parameters and protect against protein oxidative damage in the liver of diabetic rats subjected to FST.

Increased cerebral oxidative damage and decreased antioxidant defenses in ovariectomized and sham-operated rats supplemented with vitamin A.

Previous studies have linked oxidative stress with aging and aging-related processes, including menopause. Abnormalities in the redox state similar to those observed in menopausal women can be modeled experimentally with rat ovariectomy. The aim of the present study was to investigate the effects of vitamin A (retinol palmitate) supplementation (500 or 1,500 IU kg(-1) day(-1) for 30 days) on behavioral parameters and brain redox profile in ovariectomized (OVX) and sham-operated rats. Ovariectomy caused pronounced uterine atrophy and decreased locomotor/exploratory activity. Moreover, we found increased hypothalamic and frontal cortex superoxide dismutase/catalase (SOD/CAT) ratio and decreased hippocampal thiol content, accompanied by increased frontal cortex lipid oxidative damage (TBARS) in OVX rats. Vitamin A at 1,500 IUkg(-1) day(-1) decreased exploratory behavior and decreased total hippocampal thiol content in sham-operated rats, increased hippocampal SOD/CAT ratio and decreased total antioxidant potential in the hippocampus of both sham and OVX groups, and increased cortical TBARS levels in OVX rats. Thus, vitamin A may induce a pro-oxidant state in discrete brain regions of sham-operated and OVX rats. These results suggest some caution regarding the use of high doses of vitamin A supplementation during menopause.

L-NAME co-treatment prevent oxidative damage in the lung of adult Wistar rats treated with vitamin A supplementation.

Based on the fact that vitamin A in clinical doses is a potent pro-oxidant agent to the lungs, we investigated here the role of nitric oxide (NO•) in the disturbances affecting the lung redox environment in vitamin A-treated rats (retinol palmitate, doses of 1000-9000 IU•kg(-1)•day(-1)) for 28 days. Lung mitochondrial function and redox parameters, such as lipid peroxidation, protein carbonylation and the level of 3-nytrotyrosine, were quantified. We observed, for the first time, that vitamin A supplementation increases the levels of 3-nytrotyrosine in rat lung mitochondria. To determine whether nitric oxide (NO •) or its derivatives such as peroxynitrite (ONOO-) was involved in this damage, animals were co-treated with the nitric oxide synthase inhibitor L-NAME (30 mg•kg(-1), four times a week), and we analysed if this treatment prevented (or minimized) the biochemical disturbances resulting from vitamin A supplementation. We observed that L-NAME inhibited some effects caused by vitamin A supplementation. Nonetheless, L-NAME was not able to reverse completely the negative effects triggered by vitamin A supplementation, indicating that other factors rather than only NO• or ONOO- exert a prominent role in mediating the redox effects in the lung of rats that received vitamin A supplementation.

Similarities in serum oxidative stress markers and inflammatory cytokines in patients with overt schizophrenia at early and late stages of chronicity.

Schizophrenia (SZ) is a debilitating neurodevelopmental disorder that strikes at a critical period of a young person's life. Its pathophysiology could be the result of deregulation of synaptic plasticity, with downstream alterations of inflammatory immune processes regulate by cytokines, impaired antioxidant defense and increased lipid peroxidation. The aim of this study was to examine serum oxidative stress markers and inflammatory cytokines in early and late phases of chronic SZ. Twenty-two patients at early stage (within first 10 years of a psychotic episode), 39 at late stage (minimum 10 years after diagnosis of SZ) and their respective matched controls were included. Each subject had 5 ml blood samples collected by venipuncture to examined thiobarbituric acid-reactive substances (TBARS), total reactive antioxidant potential (TRAP), protein carbonyl content (PCC), Interleukins 6 and 10 (IL-6, IL-10) and tumor necrosis factor alpha (TNF-alpha). TBARS, IL-6 and PCC levels were significantly higher in patients with SZ at early and late stages than in controls. There were no differences for TRAP and TNF-alpha levels in patients with SZ at early and late stages than in controls. IL-10 levels were decreased in patients at late stage and a decrease trend in early stage was found. Results provided evidence consistent with comparable biological markers across chronic SZ. The concept of biochemical staging proposed by others for bipolar disorder is not seen in this cohort of patients with SZ, at least for cytokines and oxidative stress markers. Our findings reinforce the need of assessment of individuals in ultra high risk to develop psychosis and first-episode population.

Changes in lymphocyte HSP70 levels in women handball players throughout 1 year of training: the role of estrogen levels.

Heat shock protein 70 (HSP70) is a chaperone that maintains protein conformation during heat stress. It has recently been observed that HSP70 may be released from cells in response to increased energy demand (e.g., exercise) and/or oxidative stress. Since HSP70 levels should change in response to athletic training, we have investigated whether blood HSP70 levels in young women handball players change over a complete training season. Thirty women handball players (12-24 years old) were divided into low (≥30 pg mL(-1)) (LE) and normal (30-330 pg mL(-1)) (NE) estradiol groups. HSP70 levels in lymphocytes and plasma and blood redox parameters were evaluated over 1 year (2009), with sampling at the beginning, middle, and end of the season. We observed no changes in superoxide dismutase activity or protein carbonyl or extracellular HSP70 levels, while catalase activity increased at the middle of the season in the NE group, and the thiobarbituric acid species levels in both groups were higher at the beginning of the season than at the middle or end. The lymphocyte HSP70 content was higher at the middle and end than at the beginning of the season in the NE group and also higher in the LE group than in the NE group at the beginning of the season. These results suggest that plasma estradiol levels may play an important role in exercise training and that the intracellular HSP70 content, a biomarker for inflammation, is affected by both estradiol levels and exercise-induced oxidative stress.

Increased blood oxidative stress in experimental menopause rat model: the effects of vitamin A low-dose supplementation upon antioxidant status in bilateral ovariectomized rats.

Menopause has been reported to be associated with increased oxidative stress and metabolic disorders among women worldwide. Disarrangements in the redox state similar to those observed in women during the decline of ovarian hormonal activity can be obtained experimentally through rat bilateral ovariectomy. The search for alternative treatments to improve life quality in postmenopausal woman is really important. The aim of this study was to evaluate biochemical and oxidative stress parameters that distinguish sham-operated female rats from Wistar rats bilaterally ovariectomized (OVX). Additionally, we have also investigated the effects of retinol palmitate (a vitamin A supplement) low-dose supplementation (500 or 1500 IU/kg/day, during 30 days) upon blood and plasma antioxidant status in OVX rats. Ovariectomy caused an increase in body weight gain, pronounced uterine atrophy, decreased plasma triglycerides and increased total cholesterol levels, and reduced acid uric content. Moreover, we found increased blood peroxidase activities (catalase and glutathione peroxidase), decreased plasma non-enzymatic antioxidant defenses total reactive antioxidant potential and total antioxidant reactivity, decreased protein and non-protein SH levels, accompanied by increased protein oxidative damage (carbonyl). In addition, vitamin A low-dose supplementation was capable to ameliorate antioxidant status in OVX rats, restoring both enzymatic and non-enzymatic defenses, promoting reduction in plasma SH content, and decreasing protein oxidative damage levels. This is the first work in the literature showing that vitamin A at low dose may be beneficial in the treatment of menopause symptoms. Further studies will be made to better understand the effects of vitamin A supplementation in menopause rat model.

L-NAME cotreatment did prevent neither mitochondrial impairment nor behavioral abnormalities in adult Wistar rats treated with vitamin A supplementation.

Vitamin A has been characterized as a potential neurotoxin, because ingestion of such vitamin - or its derivatives, the retinoids - at moderate to high doses elicits a myriad of deleterious effects, from acute intoxication involving head-ache, confusion, and 'pseudo tumor cerebri' to chronic, and perhaps irreversible, abnormalities, including irritability, anxiety, depression, and suicide ideation. Nevertheless, it still remains to be found the mechanism by which vitamin A induces cognitive decline. Based on the fact that vitamin A at clinical doses is a potent pro-oxidant agent to the central nervous system, we performed the present work to analyze whether a cotreatment with L-NAME at 30 mg/kg (four times a week) was able to prevent (or minimize) the biochemical and/or behavioral disturbances resulting from a 28-day daily supplementation with retinol palmitate at doses from 1000 to 9000 IU/kg/day. Then, we investigated mitochondrial function, redox parameters, and the levels of proteins potentially involved in neurodegenerative events, as for instance α-synuclein and receptor for advanced glycation endproducts. Besides, monoamine oxidase enzyme activity was quantified in this work. We observed that L-NAME cotreatment was not completely effective in preventing the redox disturbances induced by vitamin A supplementation. Moreover, L-NAME cotreatment did not affect the behavioral deficits elicited by vitamin A supplementation. We conclude that other parameters rather than NO levels or its derivatives, as for example ONOO(-), take a more important role in mediating the negative effects triggered by vitamin A supplementation.