Decreased malondialdehyde levels in fish (Astyanax altiparanae) exposed to diesel: Evidence of metabolism by aldehyde dehydrogenase in the liver and excretion in water.

Increased malondialdehyde (MDA) levels are commonly considered an indicator of lipid peroxidation derived from oxidative stress insults promoted by exposure of fish to pollutants. However, a decrease in MDA levels after xenobiotic exposure has been also reported, an effect that is mostly attributed to enhanced antioxidant defenses. In this study, we assessed whether pollutant-mediated MDA decrease would be associated with antioxidant enhancement or with its metabolism by aldehyde dehydrogenase (ALDH) in the liver and gills of lambari (Astyanax altiparanae) exposed to diesel oil (0.001, 0.01, and 0.1 mL/L). MDA levels were decreased in the liver of lambari exposed to diesel. The activities of the antioxidant enzymes, catalase (CAT) and glutathione peroxidase (GPx), were unchanged in the liver, while that of glucose-6-phosphate dehydrogenase (G6PDH) was decreased. In contrast, levels of total glutathione (tGSH) and the activity of glutathione S-transferase (GST) were increased in the liver, which partly support antioxidant protection against lipid peroxidation. More importantly, ALDH activity increased in a concentration-dependent manner, being negatively correlated with MDA levels, indicating MDA metabolism by ALDH. In the gills, diesel exposure increased MDA and lipid hydroperoxide levels, and promoted increases in antioxidant defenses, indicating oxidative stress. Curiously, ALDH activity was undetectable in the gills, supporting the possibility of direct MDA excretion in the water by the gills. Analyses of MDA in the water revealed increased levels of MDA in the aquaria in which the fish were exposed to diesel, compared to control aquaria. A second experiment was carried out in which the fish were intraperitoneally injected with MDA (10 mg/kg) and analyzed after 1, 6, and 12 h. MDA injection caused a time-dependent decrease in hepatic MDA levels, did not alter ALDH, CAT, GPx, and GST activities, and decreased G6PDH activity and tGSH levels. In the gills, MDA injection caused a slight increase in MDA levels after 1 h, but did not alter GPx, G6PDH, and GST activities. MDA injection also enhanced CAT activity and tGSH levels in the gills. MDA concentration in water increased progressively after 1, 6, and 12 h, supporting the hypothesis of direct MDA excretion as an alternative route for MDA elimination in fish. Our results suggest that the decreased MDA levels after exposure of lambari to diesel oil pollutant probably reflects an association between enhanced antioxidant protection, MDA metabolism, and MDA excretion in water.

Thermal environment in mobile shelters with different cover types used for chicken housing at the semi-extensive rearing system.

In tropical climate countries, animal production faces a huge challenge, being the high solar irradiation levels an important factor that negatively influences the welfare and animal performance. The purpose of this research was to check the environment inside mobile shelters with different kinds of cover materials. This research has been developed at the State University of Goiás, Brazil, being used four different cover materials: DFPC, double-faced plastic canvas; PVC, polyvinyl chloride; VFB, tiles made with vegetable fiber and bitumen; and VFBW, tiles made with vegetable fiber and bitumen being the outer face painted white. Covers were placed up mobile shelters with the following dimensions: 1 m length × 1 m width × 1 m height and cover pitch of 30°. The environment was evaluated through thermal comfort indexes: enthalpy (H), temperature and humidity index (THI), black globe and humidity index (BGHI), mean radiant temperature (MRT) and thermal heat load (THL), and the measurement of thermal environmental variables (temperature of external (EST) and internal (IST) surface of the cover, dry bulb temperature (Tdb), black globe temperature (Tbg), relative humidity (RH), and wind speedy (WS)). Data analysis was performed using PROC MIXED of SAS® by analysis of variance (ANOVA), followed by the Tukey test, at 5% of significance level. There was observed beneficial effect of the usage of shading, with a decrease in air temperature and thermal comfort indexes when compared with the unshaded environment. The materials presented different thermal behavior, with better results for PVC and VFBW, that presented lower internal (IST) and external surface temperature (EST), in addition to lower black globe temperature, thermal heat load, and black globe and humidity index. PVC and VFBW were the best types of covers evaluated, with significant decreased thermal comfort indexes.

Effects of methylphenidate on the aggressive behavior, serotonin and dopamine levels, and dopamine-related gene transcription in brain of male Nile tilapia (Oreochromis niloticus).

The occurrence of pharmaceuticals in the aquatic environment has increased considerably in the last decades, causing negative biochemical, physiological, and behavioral effects in aquatic organisms. In this study, we evaluated the effects of methylphenidate (MPH) on the aggressive behavior, dopamine-related gene transcript levels, monoamine levels, and carboxylesterase transcript levels and activity in the brain of male Nile tilapia (Oreochromis niloticus). Carboxylesterase activity was also measured in the liver and gills. Fish were exposed for 5 days to MPH at 20 and 100 ng L-1. Fish exposed to 100 ng L-1 of MPH showed increased aggressiveness and decreased dopamine (DA) and serotonin (5-HT) levels. No changes were observed in plasma testosterone levels and in the transcript levels of D1 and D2 dopamine receptors, dopamine transporter (DAT), and carboxylesterase 2 (CES2). Exposure to 100 ng L-1 of MPH caused a decrease in the transcript levels of carboxylesterase 3 (CES3) and an increase in tyrosine hydroxylase (TH), while exposure to 20 ng L-1 of MPH increased the transcript levels of D5 dopamine receptor. Carboxylesterase activity was unchanged in the brain and liver and increased in the gills of fish exposed to 20 ng L-1. These results indicate that MPH at 100 ng L-1 increases aggressiveness in Nile tilapia, possibly due to a decrease in 5-HT levels in the brain and alterations in dopamine levels and dopamine-related genes.

Oxidative stress in patients with refractory temporal lobe epilepsy and mesial temporal sclerosis: Possible association with major depressive disorder?

OBJECTIVE: The objective was to evaluate the genetic and biochemical profiles associated with oxidative stress (OS) in patients with temporal lobe epilepsy with mesial temporal sclerosis (TLE-MTS) and a healthy control group, and also to verify the possible existence of association between OS markers and psychiatric disorders (PD) in group with TLE-MTS. METHODS: Forty-six patients with refractory TLE-MTS and 112 healthy controls were included. Psychiatric evaluation occurred through Diagnostical and Statistical Manual of Mental Disorders (DSM-5) criteria. A peripheral blood sample was collected for analysis of glutathione S-transferase (GST) T1/M1 polymorphisms and serum levels of malondialdehyde (MDA) and antioxidant capacity equivalent to the trolox (TEAC), serum markers of OS. Student's t-test, Fisher's exact test, Chi-square test, and Analysis of Variance (ANOVA) were used, with a significance level of P<0.05. RESULTS: The PD were observed in 27 patients of the group with TLE-MTS (58.6%); major depressive disorder (MDD) was the most frequent. Serum levels of MDA (P<0.0001) and TEAC (P<0.0001) were higher in group with TLE-MTS. When patients with MDD were compared with patients without PD, significant differences were observed between MDA (P=0.002) and TEAC (P=0.003) serum levels. Patients with TLE-MTS and MDD presented higher levels when compared with patients with TLE-MTS without PD and with another PD except MDD. CONCLUSIONS: The present study observed significantly higher serum levels of MDA and of TEAC in patients with refractory TLE-MTS in comparison with the control group. The MDD was observed as an important issue associated with higher OS levels in refractory TLE-MTS. Further studies are needed to investigate the association of OS, TLE-MTS, and PD.

Isolated and mixed effects of diuron and its metabolites on biotransformation enzymes and oxidative stress response of Nile tilapia (Oreochromis niloticus).

Diuron is one of the most used herbicide in the world, and its field application has been particularly increased in Brazil due to the expansion of sugarcane crops. Diuron has often been detected in freshwater ecosystems and it can be biodegraded into three main metabolites in the environment, the 3,4-dichloroaniline (DCA), 3,4-dichlorophenylurea (DCPU) and 3,4-dichlorophenyl-N-methylurea (DCPMU). Negative effects under aquatic biota are still not well established for diuron, especially when considering its presence in mixture with its different metabolites. In this study, we evaluated the effects of diuron alone or in combination with its metabolites, DCPMU, DCPU and 3,4-DCA on biochemical stress responses and biotransformation activity of the fish Oreochromis niloticus. Results showed that diuron and its metabolites caused significant but dispersed alterations in oxidative stress markers and biotransformation enzymes, except for ethoxyresorufin-O-deethylase (EROD) activity, that presented a dose-dependent increase after exposure to either diuron or its metabolites. Glutathione S-transferase (GST) activity was significant lower in gills after exposure to diuron metabolites, but not diuron. Diuron, DCPMU and DCA also decreased the multixenobiotic resistance (MXR) activity. Lipid peroxidation levels were increased in gill after exposure to all compounds, indicating that the original compound and diuron metabolites can induce oxidative stress in fish. The integration of all biochemical responses by the Integrated Biomarker Response (IBR) model indicated that all compounds caused significant alterations in O. niloticus, but DCPMU caused the higher alterations in both liver and gill. Our findings imply that diuron and its metabolites may impair the physiological response related to biotransformation and antioxidant activity in fish at field concentrations. Such alterations could interfere with the ability of aquatic animals to adapt to environments contaminated by agriculture.

Potential utility of melatonin as an antioxidant therapy in the management of sickle cell anemia.

This study aimed to assess antioxidant effects of melatonin treatment compared to N-acetylcysteine (NAC) and to their combination in a sickle cell suspension. Sickle erythrocytes were suspended in phosphate-buffered saline, pH 7.4, composing external control group. They were also suspended and incubated at 37°C either in the absence (experimental control group) or in the presence of NAC, melatonin and their combination at concentrations of 100 pm, 100 nm and 100 µm for 1 hr (treatment groups). The melatonin influences were evaluated by spectrophotometric [hemolysis degree, catalase (CAT), glutathione S-transferase (GST), glutathione peroxidase (GPx), glutathione reductase (GR), glucose-6-phosphate dehydrogenase (G6PDH), and superoxide dismutase (SOD) activities] and chromatographic methods [glutathione (GSH) and malondialdehyde (MDA) levels]. Incubation period was able to cause a rise about 64% on hemolysis degree as well as practically doubled the lipid peroxidation levels (P < 0.01). However, almost all antioxidants tested treatments neutralized this incubation effect observed in MDA levels. Among the antioxidant biomarkers evaluated, we observed a modulating effect of combined treatment on GPx and SOD activities (P < 0.01), which showed ~25% decrease in their activities. In addition, we found an antioxidant dose-dependent effect for melatonin on lipid peroxidation (r = -0.29; P = 0.03) and for combined antioxidant treatments also on MDA levels (r = -0.37; P = 0.01) and on SOD activity (r = -0.54; P < 0.01). Hence, these findings contribute with important insight that melatonin individually or in combination with NAC may be useful for sickle cell anemia management.

Biochemical responses, morphometric changes, genotoxic effects and CYP1A expression in the armored catfish Pterygoplichthys anisitsi after 15 days of exposure to mineral diesel and biodiesel.

Despite being considered friendlier to the environment, biodiesel fuel can be harmful to aquatic organisms, especially when combined with petroleum diesel fuel. In this work we evaluated the effects of mineral diesel fuel containing increasing concentrations of biodiesel (5% and 20%, namely B5 and B20) and pure biodiesel (B100), at concentrations of 0.001 and 0.01mLL(-1), after 15 days of exposure, in armored catfish (Pterygoplichtys anisitsi). Toxicity tests were also performed to estimate LC50 values (96h) for each compound. Biotransformation enzymes [ethoxyresorufin-O-deethylase (EROD), and glutathione S-transferase (GST)] as well as oxidative stress markers (superoxide dismutase, SOD, catalase, CAT, glutathione peroxidase, GPx, and the level of lipid peroxidation) were measured in liver and gills after treatment. Genotoxic effects were also accessed in erythrocytes using the comet assay and by evaluating the frequency of micronuclei formation. Further, the mRNA of cytochrome P450 1A (CYP1A) was also measured in liver. Mortality was not observed even exposure to concentrations as high as 6.0mLL(-1). EROD and GST activities were increased after B5 and B20 treatments; however, CYP1A mRNA induction was not observed. SOD and CAT activities were decreased, but GPx was significantly higher for all treatments in gills. There were no significant changes in lipid peroxidation, but genotoxicity markers revealed that all treatments increased comet scores. Fuels B5 and B20 increased micronuclei frequency. Our results indicate that despite being less toxic, biodiesel may cause sublethal alterations in fish that may alter long term health.

Prevalence of ß(S)-globin gene haplotypes, α-thalassemia (3.7 kb deletion) and redox status in patients with sickle cell anemia in the state of Paraná, Brazil.

The aim of this study was to determine the frequency of beta S-globin gene (ß(S) globin) haplotypes and alpha thalassemia with 3.7 kb deletion (-α(3.7kb) thalassemia) in the northwest region of Paraná state, and to investigate the oxidative and clinical-hematological profile of ß(S) globin carriers in this population. Of the 77 samples analyzed, 17 were Hb SS, 30 were Hb AS and 30 were Hb AA. The ß(S)globin haplotypes and -α(3.7kb) thalassemia were identified using polymerase chain reaction.Trolox equivalent antioxidant capacity (TEAC) and lipid peroxidation (LPO) were assessed spectophotometrically. Serum melatonin levels were determined using high-performance liquid chromatography coupled to coulometric electrochemical detection. The haplotype frequencies in the SS individuals were as follows: Bantu- 21 (62%), Benin - 11 (32%) and Atypical- 2 (6%). Bantu/Benin was the most frequent genotype. Of the 47 SS and AS individuals assessed, 17% (n = 8) had the -α(3.7kb) mutation. Clinical manifestations, as well as serum melatonin, TEAC and LPO levels did not differ between Bantu/Bantu and Bantu/Benin individuals (p > 0.05). Both genotypes were associated with high LPO and TEAC levels and decreased melatonin concentration. These data suggest that the level of oxidative stress in patients with Bantu/Bantu and Bantu/Benin genotypes may overload the antioxidant capacity.

Isolated and mixed effects of pure and formulated abamectin and difenoconazole on biochemical biomarkers of the gills of Danio rerio.

Pesticides are released into the environment daily, and their effects on nontarget species in aquatic ecosystems have been widely reported. To evaluate the adverse effects caused in adults of Danio rerio species exposed to the pesticides abamectin, difenoconazole, and their commercial formulations (Kraft 36EC® and Score 250EC®), both isolated and in mixtures, biochemical biomarkers were analyzed in the gills of organisms exposed to sublethal concentrations. To this end, the activities of the enzymes 7-ethoxyresorufin-O-deethylase (EROD), glucuronosyltransferase (UDPGT), glutathione-S-transferase (GST), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), lipid hydroperoxide (LH), and malondialdehyde (MDA), which are indicative of oxidative stress, were measured after 48 h of exposure to the different pesticide treatments. The results showed a significant increase in EROD activity and MDA levels in the gills of fish exposed to the commercial formulation of abamectin. When the fish were exposed to difenoconazole and its commercial formulation, an increase in GST, GPx, and MDA levels and a decrease in GR activity were observed in the gills. Furthermore, the responses of the biomarkers were more pronounced in organisms exposed to mixtures of both active ingredients and commercial formulations. It is concluded that the commercial formulations Kraft 36EC® and Score 250EC® and their mixtures cause significant alterations in the detoxification metabolism of exposed organisms and induce oxidative stress in fish.

Exposure to pesticides used in rice farming (bentazone, chlorantraniliprole and tebuconazole) affects biochemical biomarkers and hepatic histopathological parameters of hammertoad tadpoles (Boana faber).

Pesticides used in rice cultivation can cause negative health effects to non-target organisms representative of natural biodiversity. In this context, the present study aimed to investigate the occurrence of pesticides in surface waters from a river that flows in the middle of a rice farming-dominated area. We were also interested in evaluate biochemical and histological effects caused by exposure (16 d) to the lower and higher concentrations of the main found herbicide (bentazone, BTZ), insecticide (chlorantraniliprole, CTP) and fungicide (tebuconazole, TBZ), isolated or mixed, in Boana faber tadpoles. No significant differences were observed in the development of the animals. Tadpoles exposed to the herbicide BTZ showed higher hepatic levels of malondialdehyde (MDA). In animals exposed to CTP, MDA levels were lower than controls. Animals exposed to the fungicide TBZ showed higher hepatic activity of glutathione S-transferase and carboxylesterase (CbE), as well as higher levels of carbonyl proteins and MDA. Animals exposed to Mix showed higher activity in CbE and glucose-6-phosphate dehydrogenase activity in the liver, as well as higher levels of MDA. In the brain and muscle of tadpoles exposed to Mix, acetylcholinesterase activity was higher. Histological changes were also observed in pesticide-exposed animals, such as increased occurrence of melanomacrophages, inflammatory infiltrates and congestion. Our data evidences the contamination of natural aquatic environments by rice pesticides, and the adverse effects of main ones in B. faber tadpoles, which suggests the contribution of pesticides derived from rice cultivation to the degradation of local biodiversity health.

Prednisone and prednisolone effects on development, blood, biochemical and histopathological markers of Aquarana catesbeianus tadpoles.

Synthetic glucocorticoids are often found in surface waters and can cause harmful effects to aquatic organisms such as amphibians. In this work we evaluated the effects of the drugs prednisone (PD) and prednisolone (PL) on developmental, molecular, blood, biochemical and histological markers. Aquarana catesbeianus tadpoles were exposed for 16 days to environmentally relevant concentrations of 0, 0.1, 1 and 10 µg/L of both drugs. PD increased the transcript levels of the enzyme deiodinase III (Dio3), the hormones cortisol and T4 and delayed development. Changes in the thyroid gland occurred after tadpoles were exposed to both drugs, with a reduction in the diameter and number of follicles and an increase/or decrease in area. Also, both drugs caused a decrease in lymphocytes (L) and an increase in neutrophils (N), thrombocytes, the N:L ratio and lobed and notched erythrocytes. Increased activity of the enzymes superoxide dismutase, glutathione S-transferase and glucose 6-phosphate dehydrogenase was observed after exposure to PD. Furthermore, both drugs caused an increase in the activity of the enzymes catalase and glutathione peroxidase. However, only PD caused oxidative stress in exposed tadpoles, evidenced by increased levels of malondialdehyde and carbonyl proteins. Both drugs caused an increase in inflammatory infiltrates, blood cells and melanomacrophages in the liver. Our results indicate that PD was more toxic than PL, affecting development and causing oxidative stress.

Genetic and biochemical markers of hydroxyurea therapeutic response in sickle cell anemia.

BACKGROUND: Sickle cell anemia (SCA) presents a complex pathophysiology which can be affected by a number of modifying factors, including genetic and biochemical ones. In Brazil, there have been no studies verifying ßS-haplotypes effect on oxidative stress parameters. This study evaluated ßS-haplotypes and Hb F levels effects on oxidative stress markers and their relationship with hydroxyurea (HU) treatment in SCA patients. METHODS: The studied group was composed by 28 SCA patients. Thirteen of these patients were treated with HU and 15 of them were not. We used molecular methodology (PCR-RFLP) for hemoglobin S genotype confirmation and haplotypes identification. Biochemical parameters were measured using spectrophotometric methods (Thiobarbituric-acid-reactive substances and Trolox equivalent antioxidant capacity levels, catalase and GST activities) and plasma glutathione levels by High-performance liquid chromatography coupled to electrochemical detection. RESULTS: We found the highest frequency of Bantu haplotype (48.2%) which was followed by Benin (32.1%). We observed also the presence of Cameroon haplotype, rare in Brazilian population and 19.7% of atypical haplotypes. The protective Hb F effect was confirmed in SCA patients because these patients showed an increase in Hb F levels that resulted in a 41.3% decrease on the lipid peroxidation levels (r =-0.74, p=0.01). Other biochemical parameters have not shown differential expression according to patient's haplotypes. Bantu haplotype presence was related to the highest lipid peroxidation levels in patients (p < 0,01), but it also conferred a differential response to HU treatment, raising Hb F levels in 52.6% (p = 0.03) when compared with the group with the same molecular profile without HU usage. CONCLUSIONS: SCA patients with Bantu haplotype showed the worst oxidative status. However these patients also demonstrated a better response to the treatment with HU. Such treatment seems to have presented a "haplotype-dependent" pharmacological effect.

Combined effects of diesel and air exposure on oxidative stress parameters of mussels Perna perna (Mytilidae, Bivalvia).

This study aimed to assess the combined effect of hypoxia and exposure to diesel on biochemical parameters of Perna perna mussels. Mussels previously kept for 48 h in clean seawater were submitted to hypoxia for 24 h followed by reoxygenation in clean seawater for 48 h. The same procedure was done but using seawater containing 0.01 mL/L of diesel, before and after hypoxia. Antioxidant enzymes as well as levels of glutathione and lipid peroxidation were measured in gills and digestive glands. The neutral red retention time assay was also evaluated in hemocytes. Results showed that cycles of air exposure and reoxygenation caused oxidative stress and antioxidant modulation in both the gills and digestive glands. The presence of diesel in water triggered additional modulation of antioxidants under hypoxia and reoxygenation stress, apparently enhancing the capacity of mussels to avoid lipid peroxidation.

Influence of temperature on the biomarker responses of bullfrog tadpoles (Lithobates catesbeianus) to 2-hydroxyatrazine exposure.

The influence of temperature (25 and 32 °C) on the biomarker responses of bullfrog tadpoles (Lithobates catesbeianus) to different concentrations of the atrazine metabolite 2-hydroxyatrazine (2-HA, 0, 10, 50 and 200 ng.L-1, 16 days), was evaluated. Temperature affected the activities of superoxide dismutase, glutathione S-transferase and acetylcholinesterase. The activities of catalase, glutathione peroxidase, glucose-6-phosphate dehydrogenase and carboxylesterase presented no alterations. Frequencies of micronuclei and nuclear abnormalities were also not altered. 2-HA decreased SOD activity at 25 °C and caused histopathological changes in the liver and the kidney at both temperatures, with the kidney being more affected by the combination of higher temperature and 2-HA exposure, presenting glomerular shrinkage and an increase in Bowman's space. Our results indicate that at environmentally relevant concentrations, 2-HA can cause changes in biomarker responses as well as in the morphology of liver and kidney in L. catesbeianus tadpoles. Temperature has an important influence on biomarker response and histopathological alterations.

Fipronil impairs the GABAergic brain responses of Nile Tilapia during the transition from normoxia to acute hypoxia.

γ-aminobutyric acid (GABA) is one of the main neurotransmitters involved in the adaptation processes against the damage that hypoxia can cause to the brain. Due to its antagonist action on GABA receptors, the insecticide fipronil can turn the fish more susceptible to the negative effects of hypoxia. This study aimed to understand better if fipronil affects these GABAergic responses of Tilapia ahead to hypoxia. Oreochromis Niloticus (Nile Tilapia) were exposed for 3 and 8 h to fipronil (0.0, 0.1, and 0.5 µg.L-1 ) under normoxia (dissolved O2 > 6 mg.L-1 ) and moderate hypoxia (dissolved O2 < 2 mg.L-1 ) conditions. Briefly, hypoxia caused opposite effects on the gene transcription of the evaluated ionotropic and metabotropic GABA receptors. Unexpectedly, we obtained reduced HIF1A mRNA and brain GABA levels, mostly in the first 3 h of the experiment, for the hypoxic group compared with the normoxia one. Besides that, we also demonstrated that the insecticide fipronil impairs the brain GABAergic signaling of a hypoxia-tolerant fish during the transition from a normoxic to an acute hypoxic state. Thus, these results predict the relevant impact on the brain metabolic adaptations of fishes exposed to such stressful conditions in an aquatic environment, as well as the effects of fipronil in the GABAergic responses to hypoxia, which in turn may have ecological and physiological significance to hypoxia-tolerant fishes exposed to this insecticide.

Oxidative stress markers and apoptosis in the prostate of diabetic rats and the influence of vitamin C treatment.

Negative consequences of diabetes on the prostate such as involution are associated with diminished testosterone, insulin deficiency, and hyperglycemia. The contributions of oxidative damage, which usually increases with diabetes, are unknown for these alterations. This study evaluated the impact of streptozotocin-induced diabetes on the biomarkers of the antioxidant system of rat ventral prostate, the influence of vitamin C supplementation on these biomarkers, and on the balance between cell proliferation and death. Diabetes (D) was induced in Wistar male rats by streptozotocin (5 mg/100 g b.w., i.p.). Control animals (C) were injected with a vehicle. Vitamin C (150 mg/kg b.w./day) supplementation was introduced by gavage in diabetes (D + V) as well as control (C + V) groups. Thirty days after diabetes onset, the rats were killed and the ventral prostates were analyzed using light microscopy, immunocytochemistry, and biochemical assays for biomarkers of oxidative stress. In comparison to control groups, the levels of circulating testosterone, proliferating, and androgen receptor-positive cells decreased in diabetic groups regardless of vitamin C treatment whereas apoptosis was increased. The levels of superoxide dismutase and glutathione peroxidase did not change, but the levels of glutathione-S-transferase (GST) were increased in diabetic prostate. Vitamin C supplementation normalized GST activity and recovered the apoptotic rates in the prostate. In conclusion, GST is a good indicator of compensatory oxidant defense in the prostate at earlier stages of diabetes and vitamin C improves its activity and attenuates apoptosis in the gland.

Oxidative stress and antioxidant capacity in sickle cell anaemia patients receiving different treatments and medications for different periods of time.

To evaluate, in a longitudinal study, the profile of lipid peroxidation and antioxidant capacity markers in sickle cell anaemia patients receiving different treatments and medication over different time periods. The three groups were: patients undergoing transfusion therapy and receiving iron chelator deferasirox (DFX group, n = 20); patients receiving deferasirox and hydroxyurea (DFX + HU group, n = 10), and patients receiving only folic acid (FA group, n = 15). Thiobarbituric acid-reactive substance (TBARS) assays and trolox-equivalent antioxidant capacity (TEAC) assays were evaluated during two different periods of analysis, T0 and T1 (after ~388 days). Higher FA group TBARS values were observed compared with the DFX + HU group (p = 0.016) at T0; and at T1, higher FA group TBARS values were also observed compared with both the DFX group (p = 0.003) and the DFX + HU group (p = 0.0002). No variation in TEAC values was seen between groups, at either T0 or T1. The mean values of TBARS and TEAC for both the DFX and DFX + HU groups decreased at T1. The antioxidant effects of HU and DFX were observed by through an increase in TEAC levels in DFX and DFX + HU groups when compared with those of normal subjects. Increased TEAC values were not recorded in the FA group, and lipid peroxidation was seen to decrease after DFX and HU use.

Fish biomarker responses reflect landscape anthropic disturbance in savanna streams.

Disturbance in the landscape surrounding streams can interfere with water quality and cause harm to aquatic organisms. In this study, we evaluate the influence of land use on the genetic and biochemical biomarkers of fish in streams of Brazilian savanna (Cerrado). We also evaluated whether biomarker responses are seasonally consistent. For this purpose, individuals of the Neotropical tetra fish Astyanax lacustris were exposed in cages for 96 h, in 13 streams draining agroecosystems with different degrees of disturbance during the dry and wet seasons. After exposure, blood, liver, and gills were collected for multibiomarker analyses (micronuclei, erythrocytic nuclear abnormalities, lipid peroxidation, antioxidant enzymes, and biotransformation enzyme). The results showed that the gradient of anthropic disturbance was positively associated with genotoxic damage (erythrocytic nuclear abnormalities) and negatively associated with antioxidant and biotransformation enzymes of the liver in both seasons. No association of the gradient of anthropic disturbance with the frequency of micronuclei and for most gill enzymes was found for both seasons. Landscape disturbance was also negatively associated with water quality in the wet season. These results indicate that changes in land use interfere with the genetic and biochemical processes of organisms. Thus, the multibiomarker approach may represent an effective strategy for assessing and monitoring terrestrial landscape disturbance.

Influence of Melatonin Treatment on Cellular Mechanisms of Redox Adaptation in K562 Erythroleukemic Cells.

Melatonin (MEL) presents well-documented pleiotropic actions against oxidative stress (OS), acting indirectly through activation of transcription factors, e.g., FoxO3 and Nrf2. Thus, this study aimed to investigate the possible modulating effects of MEL on the redox signaling pathways PI3K/AKT/FoxO3 and Keap1/Nrf2/ARE in K562 erythroleukemic cells subjected to OS induction. For this, the viability, and transcript levels of genes involved in redox adaptation were evaluated in K562 cells in different periods of erythroid differentiation: under OS induction by hydrogen peroxide (100 µM H2O2); treated with 1 nM (C1) and 1 mM (C2) MEL; and associated or not with stress induction. We observed a restoration of physiological levels of Nrf2 in both MEL concentrations under OS. The C1 was related to enhanced expression of antioxidant and proteasome genes through the Nrf2-ARE pathway, while C2 to the induction of FOXO3 expression, suggesting an involvement with apoptotic pathway, according to BIM transcript levels. The effects of MEL administration in these cells showed a period and dose-dependent pattern against induced-OS, with direct and indirect actions through different pathways of cellular adaptation, reinforcing the importance of this indolamine in the regulation of cellular homeostasis, being a promising therapeutic alternative for diseases that present an exacerbated OS.

Potential Cytoprotective and Regulatory Effects of Ergothioneine on Gene Expression of Proteins Involved in Erythroid Adaptation Mechanisms and Redox Pathways in K562 Cells.

This study aimed to establish the importance of ergothioneine (ERT) in the erythroid adaptation mechanisms by appraising the expression levels of redox-related genes associated with the PI3K/AKT/FoxO3 and Nrf2-ARE pathways using K562 cells induced to erythroid differentiation and H2O2-oxidative stress. Cell viability and gene expression were evaluated. Two concentrations of ERT were assessed, 1 nM (C1) and 100 µM (C2), with and without stress induction (100 µM H2O2). Assessments were made in three periods of the cellular differentiation process (D0, D2, and D4). The C1 treatment promoted the induction of FOXO3 (D0 and 2), PSMB5, and 6 expressions (D4); C1 + H2O2 treatment showed the highest levels of NRF2 transcripts, KEAP1 (D0), YWHAQ (D2 and 4), PSMB5 (D2) and PSMB6 (D4); and C2 + H2O2 (D2) an increase in FOXO3 and MST1 expression, with a decrease of YWHAQ and NRF2 was observed. in C2 + H2O2 (D2) an increase in FOXO3 and MST1, with a decrease in YWHAQ and NRF2 was observed All ERT treatments increased gamma-globin expression. Statistical multivariate analyzes highlighted that the Nrf2-ARE pathway presented a greater contribution in the production of PRDX1, SOD1, CAT, and PSBM5 mRNAs, whereas the PI3K/AKT/FoxO3 pathway was associated with the PRDX2 and TRX transcripts. In conclusion, ERT presented a cytoprotective action through Nrf2 and FoxO3, with the latter seeming to contribute to erythroid proliferation/differentiation.