RESUMO
This study aimed to assess the antioxidant capacity of lemon flavonoid extract Eriomin® (LE) and its impact on cholesterol metabolism in the context of healthy aging. We orally treated 24-month-old male Wistar rats with an LE (40 mg/kg) suspended in 0.3 mL of sunflower oil. At the same time, control groups received an equal volume of sunflower oil (CON) or remained untreated (ICON) daily for 4 weeks. We examined LE's effects on superoxide dismutase and catalase- and glutathione-related enzyme activities, the concentration of lipid peroxides and protein carbonyls, total oxidant status (TOS) and antioxidant status (TAS), and oxidative stress index (OSI) in the liver, jejunum, and ileum. We also measured total cholesterol, its biosynthetic precursors (lanosterol, lathosterol, desmosterol), its degradation products (bile acid precursors) in the serum, liver, jejunum, and ileum, and serum phytosterols (intestinal absorption markers). LE reduced TOS, TAS, and OSI (p < 0.05) compared with control values, indicating its consistent antioxidant action in all examined organs. LE lowered hepatic desmosterol (p < 0.05) while also reducing 7α- and 24-hydroxycholesterol levels in the liver and ileum (p < 0.01). Serum cholesterol, hepatic gene expression, and the immunostaining intensity of CYP7A1 were unchanged. In conclusion, LE exerted non-enzymatic antioxidant effects and reduced cholesterol degradation, reducing its biosynthesis products, thereby maintaining serum cholesterol levels.
Assuntos
Envelhecimento , Antioxidantes , Colesterol , Citrus , Flavonoides , Fígado , Estresse Oxidativo , Extratos Vegetais , Ratos Wistar , Animais , Colesterol/sangue , Colesterol/metabolismo , Antioxidantes/metabolismo , Masculino , Ratos , Extratos Vegetais/farmacologia , Flavonoides/metabolismo , Flavonoides/farmacologia , Fígado/metabolismo , Fígado/efeitos dos fármacos , Envelhecimento/metabolismo , Citrus/química , Estresse Oxidativo/efeitos dos fármacos , Jejuno/metabolismo , Jejuno/efeitos dos fármacos , Colesterol 7-alfa-Hidroxilase/metabolismo , Colesterol 7-alfa-Hidroxilase/genéticaRESUMO
Age and sex influence serum cholesterol levels, but the underlying mechanisms remain unclear. To investigate further, we measured cholesterol, precursors (surrogate synthesis markers), degradation products (oxysterols and bile acid precursors) in serum, the liver, jejunum, and ileum, as well as serum plant sterols (intestinal absorption markers) in male and female Wistar rats (4 and 24 months old). The analysis of histomorphometric and oxidative stress parameters (superoxide dismutase, catalase, glutathione-related enzyme activities, lipid peroxide, and protein carbonyl concentrations) in the liver and jejunum offered further insights into the age- and sex-related differences. The hepatic gene expression analysis included AR, ERα, and sex-specific growth hormone-regulated (Cyp2c11 and Cyp2c12) and thyroid-responsive (Dio1, Tbg, and Spot 14) genes by qPCR. We observed age-related changes in both sexes, with greater prominence in females. Aged females had significantly higher serum cholesterol (p < 0.05), jejunum cholesterol (p < 0.05), and serum plant sterols (p < 0.05). They exhibited poorer hepato-intestinal health compared with males, which was characterized by mild liver dysfunction (hydropic degeneration, increased serum ALT, p < 0.05, and decreased activity of some antioxidant defense enzymes, p < 0.05), mononuclear inflammation in the jejunal lamina propria, and age-related decreases in jejunal catalase and glutathione peroxidase activity (p < 0.05). Aged females showed increased levels of 27-hydroxycholesterol (p < 0.05) and upregulated ERα gene expression (p < 0.05) in the liver. Our study suggests that the more significant age-related increase in serum cholesterol in females is associated with poorer hepato-intestinal health and increased jejunal cholesterol absorption. The local increase in 27-hydroxycholesterol during aging might reduce the hepatoprotective effects of endogenous estrogen in the female liver.
Assuntos
Receptor alfa de Estrogênio , Fígado , Feminino , Masculino , Ratos , Animais , Catalase/genética , Ratos Wistar , EnvelhecimentoRESUMO
With the ever-growing concern for human health and wellbeing, the prenatal period of development requires special attention since fetuses can be exposed to various metals through the mother. Therefore, this study explored the status of selected toxic (Pb, Cd, Ni, As, Pt, Ce, Rb, Sr, U) and essential trace metals (Mn, Co, Cu, Zn, Se) in the umbilical cord (UC) sera, maternal sera, and placental tissue samples of 92 healthy women with normal pregnancies. A further aim focuses on the potential transplacental transfer of these trace metals. Based on the obtained levels of investigated elements in clinical samples, it was observed that all of the trace metals cross the placental barrier and reach the fetus. Furthermore, statistical analysis revealed significant differences in levels of toxic Ni, As, Cd, U, Sr, Rb, and essential Mn, Cu, and Zn between all three types of analyzed clinical samples. Correlation analysis highlighted As to be an element with levels that differed significantly between all tested samples. Principal component analysis (PCA) was used to enhance these findings. PCA demonstrated that Cd, Mn, Zn, Rb, Ce, U, and Sr were the most influential trace metals in distinguishing placenta from maternal and UC serum samples. As, Co, and Cu were responsible for the clustering of maternal serum samples, and PCA demonstrated that the Pt level in UC sera was responsible for the clustering of these samples. Overall, the findings of this study could contribute to a better understanding of transplacental transfer of these trace metals, and shed a light on overall levels of metal exposure in the population of healthy pregnant women and their fetuses.
Assuntos
Metais Pesados , Oligoelementos , Cádmio , Feminino , Humanos , Metais Pesados/toxicidade , Placenta/química , Gravidez , Análise de Componente PrincipalRESUMO
The chemical element selenium (Se) is a nonmetal that is in trace amounts indispensable for normal cellular functioning. During pregnancy, a low Se status can increase the risk of oxidative stress. However, elevated concentrations of Se in the body can also cause oxidative stress. This study aimed to compare the effects of BSA-stabilized Se nanoparticles (SeNPs, Se0) (BSA-bovine serum albumin) and inorganic sodium selenite (NaSe, Se+4) supplementation on the histological structure of the placenta, oxidative stress parameters and the total placental Se concentration of Wistar rats during pregnancy. Pregnant females were randomized into four groups: (i) intact controls; (ii) controls that were dosed by daily oral gavage with 8.6% bovine serum albumin (BSA) and 0.125 M vit C; (iii) the SeNP group that was administered 0.5 mg of SeNPs stabilized with 8.6% BSA and 0.125 M vit C/kg bw/day by oral gavage dosing; (iv) the NaSe group, gavage dosed with 0.5 mg Na2SeO3/kg bw/day. The treatment of pregnant females started on gestational day one, lasted until day 20, and on day 21 of gestation, the fetuses with the placenta were removed from the uterus. Our findings show that the mode of action of equivalent concentrations of Se in SeNPs and NaSe depended on its redox state and chemical structure. Administration of SeNPs (Se0) increased fetal lethality and induced changes in the antioxidative defense parameters in the placenta. The accumulation of Se in the placenta was highest in SeNP-treated animals. All obtained data indicate an increased bioavailability of Se in its organic nano form and Se0 redox state in comparison to its inorganic sodium selenite form and Se+4 redox state.
Assuntos
Nanopartículas , Selênio , Animais , Feminino , Gravidez , Ratos , Biologia , Suplementos Nutricionais , Nanopartículas/química , Oxirredução , Estresse Oxidativo , Placenta , Ratos Wistar , Selênio/química , Soroalbumina Bovina/farmacologia , Selenito de Sódio/farmacologiaRESUMO
Sepsis is a life-threatening condition caused by the dysregulated and overwhelming response to infection, accompanied by an exaggerated pro-inflammatory state and lipid metabolism disturbance leading to sequential organ failure. Meldonium is an anti-ischemic and anti-inflammatory agent which negatively interferes with lipid metabolism by shifting energy production from fatty acid oxidation to glycolysis, as a less oxygen-demanding pathway. Thus, we investigated the effects of a four-week meldonium pre-treatment on faecal-induced sepsis in Sprague-Dawley male rats. Surprisingly, under septic conditions, meldonium increased animal mortality rate compared with the meldonium non-treated group. However, analysis of the tissue oxidative status did not provide support for the detrimental effects of meldonium, nor did the analysis of the tissue inflammatory status showing anti-inflammatory, anti-apoptotic, and anti-necrotic effects of meldonium. After performing tissue lipidomic analysis, we concluded that the potential cause of the meldonium harmful effect is to be found in the overall decreased lipid metabolism. The present study underlines the importance of uninterrupted energy production in sepsis, closely drawing attention to the possible harmful effects of lipid-mobilization impairment caused by certain therapeutics. This could lead to the much-needed revision of the existing guidelines in the clinical treatment of sepsis while paving the way for discovering new therapeutic approaches.
Assuntos
Fezes/microbiologia , Metilidrazinas/farmacologia , Sepse/prevenção & controle , Glândulas Suprarrenais/efeitos dos fármacos , Animais , Anti-Inflamatórios/farmacologia , Apoptose , Biomarcadores , Epinefrina/metabolismo , Ácidos Graxos/metabolismo , Inflamação , Metabolismo dos Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos , Lipidômica , Masculino , Norepinefrina/metabolismo , Estresse Oxidativo , Oxigênio/química , Ratos , Ratos Sprague-Dawley , Temperatura , Resultado do Tratamento , Triglicerídeos/metabolismo , Troponina T/sangueRESUMO
The purpose of this study was to establish reference values (RVs) for the occupationally- and environmentally-important toxic elements in the whole blood of adult Serbian population for the first time. Contaminated drinking water with arsenic, high share of smokers in the country, removing tetraethyl lead from the gasoline and war attack at the end of the twentieth century were some of the reasons to provide background information for arsenic (As), cadmium (Cd), lead (Pb), thorium (Th), and uranium (U) in the blood of the Serbian population. The whole blood samples were collected from the healthy respondents living in the Belgrade and surrounding areas of the capital (nâ¯=â¯305; w/m ratio = 154/151; mean age: 41⯱â¯2). The concentrations of toxic metals were determined by inductively coupled plasma-mass spectrometry (ICP-MS). Reference values were estimated as the lower limit (LL) and upper limit (UL) of the 95% confidence interval (CI), together with the selected percentiles (P2.5-P97.5). The obtained geometric mean (GM) for As, Cd, Pb, Th, and U were: 0.50â¯ng/g, 0.32â¯ng/g, 20.94â¯ng/g, 0.30â¯ng/g, and 0.06â¯ng/g, respectively. The influences of age, sex and lifestyle on results were considered. Women have significantly higher levels of Cd and Th than men. The increased level of Th was observed in the aged group below 40 years, while smokers had significantly higher levels of Pb and double higher level of Cd in the blood than non-smokers (pâ¯<â¯0.05). In comparison with other population groups worldwide, the Serbian population had significantly higher levels of Th and U (up to 100 times higher). These findings could contribute to better understanding of the molecular basis for the development of various health hazards, including the increased incidence of cancer among the Serbian population which need be confirmed by clinical studies.
Assuntos
Arsênio/sangue , Cádmio/sangue , Monitoramento Ambiental/métodos , Poluentes Ambientais/sangue , Chumbo/sangue , Tório/sangue , Urânio/sangue , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , SérviaRESUMO
Evaluation of trace metals at level of solid tissue can provide better information than blood or urine and, therefore, could highlight the role of metals in the etiology of organ-specific disease. The current study aimed to establish the baseline content of four essential (Mn, Cu, Zn, Se) and four toxic metals (As, Cd, Pb, U) in the healthy thyroid tissues (HTTs) by considering sex, age and smoking habits. A further aim was to examine whether differences in the content of metals exist in regard to the thyroid diseases, such as benign tumor (BT), Hashimoto's thyroiditis (HT), multinodular goiter (MNG) and thyroid cancer (TC). A total number of investigated tissue samples were 423. All metals were quantified by inductively coupled plasma-mass spectrometry (ICP-MS). It was found that the content of Cu and U was higher in HTTs of women, while the content of Zn was higher in HTTs of men. Increased content of Zn and decreased content of U was found in the group of HTTs above 50 years compared to a younger group (<50 years). Increased content of Cd, Pb and U distinguish smokers from the non-smokers. In comparison with other population groups worldwide, investigated Serbian population had up to 15 times reduced content of Se. Despite the difference in metal's profile according to biological variables, this study also demonstrated, for the first time, that each thyroid disease has its unique metal's profile. The most altered metal's content was found in tissues with HT. Contrarily, the greatest similarity in metal's content with HTTs was found in BT tissues. Based on the increased content, metal's that dominantly discriminated HTTs from the HT, MNG and TC was As, Pb and Cd, respectively. Reported results could highlight the role of toxic and essential trace metals in the not very well clarified etiology of thyroid diseases and, moreover, could provide a molecular basis for pathophysiological changes of metal's hazardous effects on thyroid health at the tissue level.
Assuntos
Metais/análise , Doenças da Glândula Tireoide/metabolismo , Glândula Tireoide/química , Neoplasias da Glândula Tireoide/química , Feminino , Humanos , Masculino , Metais/metabolismo , Pessoa de Meia-Idade , Oligoelementos/análiseRESUMO
Acute renal ischemia/reperfusion (I/R) injury is a clinical condition that is challenging to treat. Meldonium is an anti-ischemic agent that shifts energy production from fatty acid oxidation to less oxygen-consuming glycolysis. Thus, in this study we investigated the effects of a four-week meldonium pre-treatment (300 mg/kg b.m./day) on acute renal I/R in male rats (Wistar strain). Our results showed that meldonium decreased animal body mass gain, food and water intake, and carnitine, glucose, and lactic acid kidney content. In kidneys of animals subjected to I/R, meldonium increased phosphorylation of mitogen-activated protein kinase p38 and protein kinase B, and increased the expression of nuclear factor erythroid 2-related factor 2 and haeme oxygenase 1, causing manganese superoxide dismutase expression and activity to increase, as well as lipid peroxidation, cooper-zinc superoxide dismutase, glutathione peroxidase, and glutathione reductase activities to decrease. By decreasing the kidney Bax/Bcl2 expression ratio and kidney and serum high mobility group box 1 protein content, meldonium reduced apoptotic and necrotic events in I/R, as confirmed by kidney histology. Meldonium increased adrenal noradrenaline content and serum, adrenal, hepatic, and renal ascorbic/dehydroascorbic acid ratio, which caused complex changes in renal lipidomics. Taken together, our results have confirmed that meldonium pre-treatment protects against I/R-induced oxidative stress and apoptosis/necrosis.
Assuntos
Injúria Renal Aguda/tratamento farmacológico , Metilidrazinas/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/patologia , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Masculino , Norepinefrina/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Ratos , Ratos Wistar , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologiaRESUMO
We investigated in the liver of dice snakes during pre- and post-hibernation changes in the following antioxidant parameters: total, manganese and copper zinc containing superoxide dismutases (Tot SOD, MnSOD, CuZn SOD, respectively), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GR) and the concentrations of total glutathione (GSH) and sulfhydryl groups (-SH). In addition, we examined the expression of phase I biotransformation enzyme cytochrome P4501A (CYP1A) and the activity of phase II biotransformation enzyme glutathioneS-transferase (GST), the level of lipid peroxidation (by measuring the thiobarbituric acid-reactive substances (TBARS)), cholinesterase activity (ChE) and metallothionein expression (MT). We also measured the concentrations of heavy metals, including Al, Cd, As, Co, Cr, Cu, Fe, Mn, Mo, Ni, Pb and Zn in the water and snake liver during both periods. During the post-hibernation period, the activities of Tot SOD, CuZn SOD and GST and the concentration of GSH were significantly decreased, while GSH-Px and GR activities, the concentrations of -SH groups and TBARS were significantly increased. The activities of Mn SOD, CAT and ChE, and the relative amounts of CYP1A and MT did not significantly change during the investigated periods. The observed differences in the examined parameters probably represent adaptive physiological responses to sudden changes in tissue oxygenation during arousal from hibernation. Our findings also indicate that the accumulated metals modulated the responses of the examined parameters during the investigated periods.
Assuntos
Adaptação Fisiológica , Colubridae/fisiologia , Hibernação/fisiologia , Metais Pesados/metabolismo , Animais , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Catalase/metabolismo , Colinesterases/metabolismo , Colubridae/metabolismo , Feminino , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Glutationa Redutase/metabolismo , Glutationa Transferase/metabolismo , Peroxidação de Lipídeos , Fígado/metabolismo , Metalotioneína/metabolismo , Metais Pesados/análise , Estresse Oxidativo , Superóxido Dismutase/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Água/químicaRESUMO
Heavy metal pollution of the aquatic environment is of great concern worldwide. Heavy metals are capable of inducing oxidative stress by increasing the formation of reactive oxygen species (ROS), and directly affecting the antioxidant defense system (AOS) in living organisms. The frog Pelophylax kl. esculentus is a semiaquatic species with semipermeable skin and a complex lifecycle, and represents a potentially useful bioindicator organism. The aim of this study was to investigate the accumulation of several heavy metals (Cd, Co, Cr, Cu, Fe, Hg, Ni, Pb and Zn), and their effects on selected parameters of the AOS, including the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GR), phase II biotransformation enzyme glutathione-S-transferase (GST), the total glutathione (GSH) contents and sulfhydryl (SH) group concentrations, as well as cholinesterases (ChEs) activities in the liver, skin and muscle of P. kl. esculentus. Frog samples were collected at two sites (the Danube-Tisza-Danube canal (DTDC) and the river Ponjavica) in Serbia, which are characterized by different levels of metal pollution. Differences between the metal contents in different tissues showed that the skin of frogs from the DTDC accumulated statistically higher concentrations of Cd, Cu, Pb and Zn, while only the Fe concentration was lower. No significant differences between metal concentrations in muscle tissues of frogs from the DTDC and Ponjavica were observed. Examination of the parameters of the AOS revealed that frogs from the DTDC had higher concentrations of GSH in the liver and of SH groups in the skin and muscle, whereas the activities of the antioxidative enzymes SOD, GHS-Px and GR in the liver and of GR in the skin were lower than in frogs from the Ponjavica. The relationship between metal concentrations and AOS parameters showed the highest number of correlations with GSH, GR and CAT, and with Ni, Zn, Hg, Cr and Cd. Based on the results in this study, we concluded that increased concentrations of heavy metals in frog tissues can alter the AOS, which leads to higher concentrations of GSH and SH groups and lower activities of antioxidative enzymes. The response of the AOS to metal pollutants allowed us to make a distinction between different frog tissues, and to conclude that the liver and skin are more suitable for assessing metal-induced oxidative stress in frogs than muscle.
Assuntos
Metais Pesados/toxicidade , Ranidae/metabolismo , Poluentes Químicos da Água/toxicidade , Animais , Catalase/metabolismo , Colinesterases/metabolismo , Monitoramento Ambiental , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Glutationa Redutase/metabolismo , Glutationa Transferase/metabolismo , Fígado/metabolismo , Metais Pesados/análise , Músculos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Rios , Sérvia , Pele/metabolismo , Compostos de Sulfidrila/metabolismo , Superóxido Dismutase/metabolismo , Poluentes Químicos da Água/análiseRESUMO
Metals are involved in the formation of reactive oxygen species and can induce oxidative stress. The aim of this study was to assess the effects of several metals on oxidative stress in the skin and muscle of the Pelophylax esculentus "complex" frogs (parental species Pelophylax ridibundus, Pelophylax lessonae, and their hybrid Pelophylax esculentus) that inhabit the wetland Obedska Bara in Serbia, and the potential use of these species as bioindicator organisms in biomonitoring studies. The biomarkers of oxidative stress (SOD, CAT, GSH-Px, GR, GST activities and GSH, SH concentrations) and cholinesterase activity were investigated. The concentrations of nine metals (Fe, Cu, Zn, As, Cd, Cr, Hg, Ni, and Pb) were measured in the water and tissues. Correlations were established between metals and biomarkers in the tissues. The results of metal accumulation distinguished the skin of P. lessonae and muscle of P. ridibundus from other P. esculentus complex species. The oxidative stress biomarkers observed in P. ridibundus and P. esculentus had greater similarity than in P. lessonae. The P. lessonae displayed the highest number of correlations between biomarkers and metals. The results of tissue responses revealed that skin was more susceptible to metal-induced oxidative stress, with only exception of As. In the light of these findings, we can suggest the use of P. esculentus complex species as a biomonitoring species in studies of metal accumulation and metal-induced oxidative stress, but with special emphasis on P. lessonae.
Assuntos
Monitoramento Ambiental , Estresse Oxidativo/fisiologia , Rana esculenta/fisiologia , Poluentes Químicos da Água/metabolismo , Animais , Metais/análise , Metais/metabolismo , Metais/toxicidade , Músculos/metabolismo , Sérvia , Pele/metabolismo , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade , Áreas AlagadasRESUMO
To compare the effects of organic selenium nanoparticles (SeNPs, Se0) and inorganic sodium selenite (NaSe, Na2SeO3, Se4+) on the antioxidant response in maternal and fetal rat liver, pregnant females were treated with two forms of selenium (Se) at equivalent doses during gestation (0.5 mg SeNPs or 0.5 mg NaSe/kg body weight/day). Structural parameters of the liver of gravid females and their fetuses were examined in a sex-specific manner. The oxidative stress parameters superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GR), glutathione S-transferase (GST), total glutathione (GSH) and sulfhydryl groups (SH) were established. In addition, the Se concentration was determined in the blood, liver, urine and feces of the gravid females and in the liver of the fetuses. The structure of the liver of gravid females remained histologically the same after supplementation with both forms of Se, while the oxidative stress in the liver was significantly lower after the use of SeNPs compared to NaSe. Immaturity of fetal antioxidant defenses and sex specificity were demonstrated. This study provides a detailed insight into the differences in the bioavailability of the nano form of Se compared to sodium selenite in the livers of pregnant females and fetuses.
RESUMO
The activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GR), and glutathione S-transferase (GST), as well as the concentrations of sulfhydryl (SH) groups and glutathione (GSH) were analyzed in five age classes of the Mediterranean centipede Scolopendra cingulata as follows: embryo, adolescens, maturus junior, maturus, and maturus senior. The data obtained showed the presence of SOD, CAT, GSH-Px, GR, GST, and SH groups in embryos. The transition from embryo to adolescens was accompanied by an increase in the activities of all studied enzymes, in response to the increased production of ROS due to the increased metabolic activity of the centipede associated with growth and development. Our results show that trends in antioxidant enzyme (AOE) activities were not uniform among adult age classes, suggesting that maturus junior, maturus, and maturus senior differentially respond and/or have different susceptibility to ROS. On the other hand, GSH concentration in embryos was undetectable, highest in adolescens and decreased in the latter part of life. Pearson correlation analysis in embryos showed that the activities of the AOEs were strongly and positively correlated with each other but negatively correlated with GSH and SH groups. At later age classes, SOD, CAT, GSH-Px, GR, GSH, and SH groups were no longer significantly correlated with GST. In the discriminant analysis, the variables that separated the age classes were GR, GST, SH groups, and body length. Body length was directly related to the age of individuals, clearly indicating that development/aging affects the regulation of antioxidant defense in this species.
Assuntos
Antioxidantes , Xenarthra , Animais , Antioxidantes/metabolismo , Quilópodes/metabolismo , Espécies Reativas de Oxigênio , Catalase/metabolismo , Glutationa/metabolismo , Superóxido Dismutase/metabolismo , Glutationa Peroxidase/metabolismo , Glutationa Redutase/metabolismo , Xenarthra/metabolismo , Glutationa Transferase/metabolismoRESUMO
Studies indicate that the soil, water and consequently foodstuffs in Serbia are significantly poor in zinc (Zn), and thus, it is likely that there is a Zn deficiency in the Serbian population. This study examined the Zn status in multiple clinical samples, including body fluids (serum, cerebrospinal fluid), whole blood and Zn-rich solid tissues (thyroid and brain tissue). Differences between sex and age were also considered, and comparative analysis of Zn status with other world populations was performed. Serum samples from a large number of Serbian adults approximately had twofold lower Zn amounts when compared to other populations. A similar trend was obtained for whole blood. Males had significantly higher amounts of Zn in serum, whole blood and thyroid tissue samples than females. Higher amounts of Zn were observed in the group older than 50 years. Importantly, in thyroid and brain tissues, Zn was 10- and 20-fold lower, respectively, than reported in the literature. Our results indicate that the population in Serbia could be considered Zn deficient. Therefore, adequate oral Zn supplementation and/or foodstuff fortification should be considered to prevent the deleterious effects caused by Zn deficiency.
Assuntos
Líquidos Corporais , Zinco , Feminino , Humanos , Masculino , Sérvia/epidemiologia , Solo , Glândula TireoideRESUMO
There are only a few reports examining the impact of oxidative stress in patients with benign and malignant brain tumors. In this study we investigated whether there are changes in antioxidant system (AOS) parameters and key trace elements between control, benign and malignant brain tissues. The study also aimed to examine correlations between the analyzed parameters. The study enrolled both types of brain tumors, benign tumors (BT) and malignant tumors (MT). The results were compared with control tissue (CT) without tumor infiltration collected from patients with BT. The following antioxidant parameters were determined: activities of total, manganese-containing, and copper/zinc-containing superoxide dismutase (TotSOD, MnSOD and CuZnSOD), activities of catalase, glutathione peroxidase, glutathione S-transferase, glutathione reductase and acetylcholine esterase (AChE), the concentrations of glutathione and sulfhydryl groups and of manganese (Mn), copper (Cu), zinc (Zn), and selenium (Se). BT and MT had altered activities/levels of multiple AOS parameters as compared to CT, indicating that tumor cells had an altered cell metabolism and changes in AOS represent adaptive response to increased oxidative stress. Low MnSOD and AChE and high GST activities were significant for distinguishing between MT and CT. Malignant tissue was also characterized by lower Mn and Cu concentrations relative to CT and BT. Principal Component Analysis clearly discriminated BT from CT and MT (PC1, 66.97%), while PC2 clearly discriminated CT from BT and MT (33.03%). Most correlative relationships were associated with Se in the BT group and Cu in the MT group. The results of this study reveal differences between the AOS parameters and the essential trace elements between the analyzed groups. The observed dysregulations show that oxidative stress could have an important role in disrupting brain homeostasis and its presence in the pathogenesis of benign and malignant brain tumors.
Assuntos
Antioxidantes/metabolismo , Neoplasias Encefálicas/metabolismo , Encéfalo/metabolismo , Enzimas/metabolismo , Oligoelementos/análise , Acetilcolinesterase/metabolismo , Adulto , Estudos de Casos e Controles , Catalase/metabolismo , Cobre/análise , Feminino , Regulação Enzimológica da Expressão Gênica , Glutationa/análise , Glutationa Peroxidase/metabolismo , Glutationa Redutase/metabolismo , Glutationa Transferase/metabolismo , Humanos , Masculino , Manganês/análise , Pessoa de Meia-Idade , Selênio/análise , Superóxido Dismutase/metabolismo , Zinco/análiseRESUMO
Acute ischemia/reperfusion (I/R) liver injury is a clinical condition challenging to treat. Meldonium is an anti-ischemic agent that shifts energy production from fatty acid oxidation to less oxygen-consuming glycolysis. Thus, we investigated the effects of a 4-week meldonium pre-treatment (300 mg/kg b.m./day) on the acute I/R liver injury in Wistar strain male rats. Our results showed that meldonium ameliorates I/R-induced liver inflammation and injury, as confirmed by liver histology, and by attenuation of serum alanine- and aspartate aminotransferase activity, serum and liver high mobility group box 1 protein expression, and liver expression of Bax/Bcl2, haptoglobin, and the phosphorylated nuclear factor kappa-light-chain-enhancer of activated B cells. Through the increased hepatic activation of the nuclear factor erythroid 2-related factor 2, meldonium improves the antioxidative defence in the liver of animals subjected to I/R, as proved by an increase in serum and liver ascorbic/dehydroascorbic acid ratio, hepatic haem oxygenase 1 expression, glutathione and free thiol groups content, and hepatic copper-zinc superoxide dismutase, manganese superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase activity. Based on our results, it can be concluded that meldonium represent a protective agent against I/R-induced liver injury, with a clinical significance in surgical procedures.
Assuntos
Regulação da Expressão Gênica/efeitos dos fármacos , Hepatopatias/tratamento farmacológico , Fígado/metabolismo , Metilidrazinas/farmacologia , Traumatismo por Reperfusão/tratamento farmacológico , Doença Aguda , Animais , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/patologia , Fígado/patologia , Hepatopatias/metabolismo , Hepatopatias/patologia , Masculino , Ratos , Ratos Wistar , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologiaRESUMO
This study investigated seasonal variations of antioxidant defense enzyme activities: total, manganese, copper zinc containing superoxide dismutase (Tot SOD, Mn SOD, CuZn SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GR) and biotransformation phase II enzyme glutathione-S-transferase (GST) activity in the liver and white muscle of red mullet (Mullus barbatus). The investigations were performed in winter and spring at two localities: Near Bar (NB) and Estuary of the River Bojana (EB) in the Southern Adriatic Sea. At both sites, Mn SOD, GSH-Px, GR and GST activities decreased in the liver in spring. In the white muscle, activities of Mn SOD, GSH-Px, GR and GST in NB decreased in spring. GR decreased in spring in EB, while CAT activity was higher in spring at both sites. The results of Principal Component Analysis (PCA) based on correlations indicated a clear separation of various sampling periods for both investigated tissues and a marked difference between two seasons. Our study is the first report on antioxidant defense enzyme activities in the red mullet in the Southern Adriatic Sea. It indicates that seasonal variations of antioxidant defense enzyme activities should be used in further biomonitoring studies in fish species.
Assuntos
Fígado/enzimologia , Fibras Musculares de Contração Rápida/enzimologia , Oxirredutases/metabolismo , Estações do Ano , Smegmamorpha/fisiologia , Animais , Oceanos e MaresRESUMO
The pathogenesis of malignant brain tumors (MBTs) should be better understood due to the evident association between prolonged exposure to metals and increased risk of MBTs. The present research aimed to find trace metals that could contribute to the pathogenesis of MBTs. Essential trace elements (Mn, Co, Zn, Cu, Se) and relevant toxic metals (Al, Ni, As, Sr, Cd, Ce, Pt, Pb, U) in the serum, cell fraction (CF), cerebrospinal fluid (CSF) and cancerous tissue (CT) samples of MBT patients were analyzed. The results were compared with sex- and age-matched control groups. For the first time, this research showed that elemental profiles of serum, CF, CSF and CT samples in MBT patients were significantly altered compared to the appropriate controls, as well as that higher contents of trace elements (particularly Mn, Se, and Pb) could be involved in the pathogenesis of MBTs. However, the most noticeable change found was the elevated U content, indicating its considerable role as a major cerebral discriminator of the presence/absence of MBTs. The U/Se ratio could be considered as an appropriate blood marker in diagnostic MBT evaluation. The reported results could contribute to better understanding of the poorly understood pathogenesis of MBTs. Furthermore, the reported results could highlight a molecular basis for the pathophysiological changes caused by the hazardous effects of trace metals on brain homeostasis.
Assuntos
Neoplasias Encefálicas/sangue , Neoplasias Encefálicas/líquido cefalorraquidiano , Oligoelementos/sangue , Oligoelementos/líquido cefalorraquidiano , Adulto , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Neoplasias Encefálicas/patologia , Feminino , Homeostase/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Oligoelementos/toxicidadeRESUMO
This study was aimed to determine reference values (RVs) for the manganese (Mn), copper (Cu), zinc (Zn), and selenium (Se) in the whole blood (B) and serum (S) samples of the Serbian population. Blood specimens were collected from healthy persons (n = 295; women/men ratio = 149/146; mean age: 42 ± 2 years). The RVs were calculated as lower limit (LL) and upper limit (UL) of the 95% confidence interval (CI) and were expressed as percentiles (P) in the range from P2.5 to P97.5. The influences of sex, age, and smoking habits on element profiles were considered. It was found that the contents of B-Cu and S-Cu were higher in women, while the contents of B-Zn and S-Zn were higher in men. Both trace elements were significantly increased in a group of persons above 40 when compared to a younger persons (≤ 40 years). According to smoking habits, increased content was found only for S-Mn in the nonsmoker's group (p < 0.05). Comparing our results to the results reported in other population groups worldwide, the Serbian population had significantly reduced content of Se in both types of samples. This finding could highlight the deficiency of Se in the investigated Serbian population and could contribute to the better understanding of the molecular basis for the increased incidence of thyroid and other diseases in which selenium plays a key role.
Assuntos
Cobre/sangue , Manganês/sangue , Selênio/deficiência , Oligoelementos/sangue , Zinco/sangue , Adulto , Distribuição por Idade , Feminino , Voluntários Saudáveis , Humanos , Masculino , Valores de Referência , Selênio/sangue , Distribuição por Sexo , Adulto JovemRESUMO
INTRODUCTION: Any substance that induces production of free radicals can be a potential cause of brain damage. The aim of our study was to investigate the relationship between some metal ions and oxidative stress biomarkers in the blood of patients with brain tumor and hydrocephalus. MATERIAL AND METHODS: Our study included 27 control subjects, 24 patients with brain tumor and 21 patients with hydrocephalus. The activities of superoxide dismutase (CuZn SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GR), glutathione S-transferase (GST) and acetyl cholinesterase (AChE), as well as concentrations of reduced glutathione (GSH), lipid peroxides (TBARS) and sulfhydryl groups (SH) were analyzed in the plasma and red blood cells (RBCs) of patients. We also determined the concentrations of Mn, Ni, Co, Cu, Zn, As, Se, Cd, Hg and Fe. RESULTS: The higher activity of SOD and concentration of GSH in both investigated groups could indicate higher oxidative stress. We also observed decreased levels of SH groups in both groups of patients. In both groups of patients we detected decreased concentrations of Ni, Co, Zn and Fe (and Mn in brain tumor patients) and increased concentrations of As, Se and Cd in the blood. Interestingly, we observed a higher concentration of Cd in both plasma and RBCs of hydrocephalus patients compared to the patients with brain tumor. CONCLUSIONS: There are strong correlations between some metal ion concentrations and certain oxidative stress biomarkers in the blood of patients, which supports our hypothesis, but the observed trend needs to be further investigated.