Carlos Eduardo Schnorr

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 persons 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.

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.

Vitamin A supplementation in rats under pregnancy and nursing induces behavioral changes and oxidative stress upon striatum and hippocampus of dams and their offspring

Vitamin A is important for both development and maintenance of adult brain homeostasis. However, excessive vitamin A exposure has been linked to cognitive impairments and may induce congenital defects, including neuronal malformations. Recently, we demonstrated that vitamin A supplementation is able to alter behavioral parameters and induce a pro-oxidant state in hippocampus and striatum of adult male rat. Thus, the aim of the present work was to investigate the effects of vitamin A supplementation in pregnant and nursing rats on maternal and offspring striatum and hippocampus. Wistar female rats (7 per group) were orally supplemented with retinyl palmitate (2500, 12,500 and 25,000 IU/kg/day) or saline (control) throughout pregnancy and nursing. Homing test was performed at postnatal days (PND) 5 and 10 for offspring, while open field test (OFT) was carried out at PND19 and 20 for dams and offspring, respectively. Redox parameters were evaluated at PND21 for both. Vitamin A supplementation during pregnancy and nursing increased superoxide dismutase/catalase (SOD/CAT) ratio and oxidative damage in maternal and offspring striatum and hippocampus. Additionally, supplementation induced behavioral alterations. In conclusion, we suggest some caution regarding vitamin A intake during pregnancy and breastfeeding, since oxidative stress can disturb several biological phenomena, including neuronal signaling and neurotransmission, which may induce several behavioral deficits.

Increased 3-nitrotyrosine levels in mitochondrial membranes and impaired respiratory chain activity in brain regions of adult female rats submitted to daily vitamin A supplementation for 2 months

Vitamin A supplementation among women is a common habit worldwide in an attempt to slow aging progression due to the antioxidant potential attributed to retinoids. Nonetheless, vitamin A elicits a myriad of side effects that result from either therapeutic or inadvertent intake at varying doses for different periods. The mechanism behind such effects remains to be elucidated. In this regard, we performed the present work aiming to investigate the effects of vitamin A supplementation at 100, 200, or 500IU/kgday(-1) for 2 months on female rat brain, analyzing tissue lipid peroxidation levels, antioxidant enzyme activities (both Cu/Zn-superoxide dismutase - SOD - and Mn-SOD); glutathione S-transferase (GST) and monoamine oxidase (MAO) enzyme activity; mitochondrial respiratory chain activity and redox parameters in mitochondrial membranes, as well as quantifying α- and β-synucleins, β-amyloid peptide(1-40), immunoglobulin heavy-chain binding protein/78kDa glucose-regulated protein (BiP/GRP78), receptor for advanced glycation end products (RAGE), D2 receptor, and tumor necrosis factor-α (TNF-α) contents in rat frontal cortex, hippocampus, striatum, and cerebellum. We observed increased lipid peroxidation marker levels, altered Cu/Zn-SOD and Mn-SOD enzyme activities, mitochondrial nitrosative stress, and impaired respiratory chain activity in such brain regions. On the other hand, we did not find any change in MAO and GST enzyme activities, and on α- and β-synucleins, β-amyloid peptide(1-40), GRP78/BiP, RAGE, D2 receptor, and TNF-α contents. Importantly, we did not observed any evidence regarding an antioxidant effect of such vitamin at low doses in this experimental model. The use of vitamin A as an antioxidant therapy among women needs to be reexamined.

Vitamin A supplementation to pregnant and breastfeeding female rats induces oxidative stress in the neonatal lung.

Vitamin A is an essential micronutrient that regulates many biological processes through modulation of retinoic acid receptor-responsive genes. Vitamin A acts as a systemic antioxidant, participating in the modulation of diverse redox mechanisms involved in physiological and pathological processes. Different studies, however, observed that vitamin A and other retinoids may induce pro-oxidant/deleterious actions under certain conditions, leading to impairment of brain and lung function. Here, we studied the effect of vitamin A treatment at oral doses of 100 IU/kg, 200 IU/kg, and 300 IU/kg to female rats (Rattus norvegicus) during pregnancy and lactation on oxidative parameters of lungs from the offspring vitamin A supplementation induced increases in lipoperoxidation, protein carbonyl, activities of the antioxidant enzymes superoxide dismutase and catalase (200 IU/kg, and 300 IU/kg), and decreased sulphydryl protein (500 IU/kg) content in the neonatal lung.

Guarana (Paullinia cupana Mart.) prevents β-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 Alzheimers disease (AD). Previous studies have shown that AGEs exacerbate β‐amyloid (Aβ) aggregation and AGE‐related cross‐links are also detected in senile plaques. Acrolein (ACR) is an α, β‐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, β‐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. Copyright

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

Abstract 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.

Preventive supplementation with fresh and preserved peach attenuates CCl4-induced oxidative stress, inflammation and tissue damage

The present study was elaborated to comparatively evaluate the preventive effect of different peach-derived products obtained from preserved fruits (Syrup and Preserve Pulp Peach [PPP]) and from fresh peels and pulps (Peel and Fresh Pulp Peach [FPP]) in a model of liver/renal toxicity and inflammation induced by carbon tetrachloride (CCl4) in rats. Tissue damage (carbonyl, thiobarbituric acid reactive species and sulfhydril), antioxidant enzymes activity (catalase and superoxide dismutase) and inflammatory parameters [tumor necrosis factor (TNF)-α and interleukin (IL)-1β levels, and receptor for advanced glycation end-products (RAGE) and nuclear factor (NF)κB-p65 immunocontent] were investigated. Our findings demonstrated that Peel, PPP and FPP (200 or 400 mg/kg) daily administration by oral gavage for 30 days conferred a significant protection against CCl4-induced antioxidant enzymes activation and, most importantly, oxidative damage to lipids and proteins as well as blocked induction of inflammatory mediators such as TNF-α, IL-1β, RAGE and NFκB. This antioxidant/anti-inflammatory effect seems to be associated with the abundance of carotenoids and polyphenols present in peach-derived products, which are enriched in fresh-fruit-derived preparations (Peel and FPP) but are also present in PPP. The Syrup - which was the least enriched in antioxidants - displayed no protective effect in our experiments. These effects cumulated in decreased levels of transaminases and lactate dehydrogenase leakage into serum and maintenance of organ architecture. Therefore, the herein presented results show evidence that supplementation with peach products may be protective against organ damage caused by oxidative stress, being interesting candidates for production of antioxidant-enriched functional foods.

The effects of vitamin A supplementation to rats during gestation and lactation upon redox parameters: Increased oxidative stress and redox modulation in mothers and their offspring

Vitamin A is an essential nutrient required in adequate amounts for reproduction and development. Subtle variations in the status of maternal nutrition may affect physiological and metabolic parameters in the fetus. Evidence suggests a key role for oxidative stress in these events. Literature is controversial about the effects of vitamin A supplementation. Here, we studied the effects of vitamin A supplementation on female Wistar rats during gestation and lactation on oxidative stress parameters of maternal and offspring tissues. Rats received daily doses of vitamin A at 2500, 12,500 and 25,000IU/kg. We observed an increase of oxidative damage markers in the reproductive tissues and plasma of dams. The activity of glutathione-S-transferase was modulated by vitamin A supplementation. It was found to be increased in the liver of dams and decreased in the kidneys of mothers and offspring. In pups, supplementation decreased the total antioxidant potential of the liver along with decreased superoxide dismutase/catalase activity ratio in the kidney. The levels of lipoperoxidation were increased in male offspring, but decreased in female pups. Collectively, the results suggest that excessive vitamin A intake during gestation and lactation might be toxic for mothers with adverse effects for the developing offspring.

Long-term vitamin A supplementation at therapeutic doses induces mitochondrial electrons transfer chain (METC) impairment and increased mitochondrial membrane-enriched fraction (MMEF) 3-nitrotyrosine on rat heart

Abstract The aim of the present study was to compare electrons flux and oxidative/nitrosative stress parameters on the heart among rats supplemented with vitamin A and one not supplemented long-term. Vitamin A has important roles for the cardiovascular system as well as antioxidant properties. However, pro-oxidant properties have been reported. Male adult rats were treated with four different doses of retinyl palmitate (1000–9000 IU/Kg/day) or saline (control) for 28 days and the heart was removed for analysis. Electrons flux and oxidative/nitrosative stress parameters were evaluated and statistics were conducted with Anova one-way followed by Dunnets post hoc and significance level of p<0.05. The supplementation induced increase on lipids/proteins oxidation and mitochondrial 3-nitrotyrosine content, an imbalance on enzymatic activity and a decrease on respiratory chain complexes activities. The results suggest that vitamin A induces oxidative/nitrosative stress and mitochondrial impairment on a cardiac level.