Lemon Flavonoid Extract Eriomin Improves Pro/Antioxidant Status and Interferes with Cholesterol Metabolism without Affecting Serum Cholesterol Levels in Aged Rats.

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.

Differences in Cholesterol Metabolism, Hepato-Intestinal Aging, and Hepatic Endocrine Milieu in Rats as Affected by the Sex and Age.

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.

Examination of Trace Metals and Their Potential Transplacental Transfer in Pregnancy.

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.

The Effects of BSA-Stabilized Selenium Nanoparticles and Sodium Selenite Supplementation on the Structure, Oxidative Stress Parameters and Selenium Redox Biology in Rat Placenta.

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.

Lipidomics Provides New Insight into Pathogenesis and Therapeutic Targets of the Ischemia-Reperfusion Injury.

Lipids play an essential role in both tissue protection and damage. Tissue ischemia creates anaerobic conditions in which enzyme inactivation occurs, and reperfusion can initiate oxidative stress that leads to harmful changes in membrane lipids, the formation of aldehydes, and chain damage until cell death. The critical event in such a series of harmful events in the cell is the unwanted accumulation of fatty acids that leads to lipotoxicity. Lipid analysis provides additional insight into the pathogenesis of ischemia/reperfusion (I/R) disorders and reveals new targets for drug action. The profile of changes in the composition of fatty acids in the cell, as well as the time course of these changes, indicate both the mechanism of damage and new therapeutic possibilities. A therapeutic approach to reperfusion lipotoxicity involves attenuation of fatty acids overload, i.e., their transport to adipose tissue and/or inhibition of the adverse effects of fatty acids on cell damage and death. The latter option involves using PPAR agonists and drugs that modulate the transport of fatty acids via carnitine into the interior of the mitochondria or the redirection of long-chain fatty acids to peroxisomes.

The Effects of a Meldonium Pre-Treatment on the Course of the Faecal-Induced Sepsis in Rats.

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.

Oxidative stress in Pelophylax esculentus complex frogs in the wild during transition from aquatic to terrestrial life.

During life, anuran individuals undergo drastic changes in the course of transition from aquatic to terrestrial habitat, when they are faced with metabolically demanding processes (growth, responses to developmental pressures), which result in increased production of reactive oxygen species (ROS), signaling molecules involved in development that can induce oxidative damage and stress. This situation can be further complicated by environmental influences. The aim of this study was to investigate oxidative stress parameters in naturally developing Pelophylax esculentus complex frogs during four developmental periods: premetamorphosis, prometamorphosis, metamorphic climax and juvenile stage, in order to examine changes in the response of the antioxidative system (AOS) and oxidative damage during the transition from aquatic to terrestrial life. Results show that ontogenetic shifts in anurans are accompanied by different levels of damage and AOS responses, which vary from the increased first-line enzymatic activities during the early period of development (premetamorphosis), through increased changes in the non-enzymatic complement during the metamorphic climax, to changes in both the enzymatic and non-enzymatic components observed in juvenile individuals. Premetamorphic individuals and individuals in metamorphosis displayed higher levels of lipid peroxidation, indicating that direct exposure to the environment for the first time and the modulation of organs are the most susceptible stages for oxidative damage. On the other hand, lower oxidative damage in juveniles points to the ability of their AOS to efficiently respond to challenges of the terrestrial environment. This study highlights the importance of ROS and the AOS of anurans in response to different developmental and/or environmental pressures that individuals face.

The Effects of Meldonium on the Renal Acute Ischemia/Reperfusion Injury in Rats.

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.

Oxidative stress biomarkers, cholinesterase activity and biotransformation enzymes in the liver of dice snake (Natrix tessellata Laurenti) during pre-hibernation and post-hibernation: A possible correlation with heavy metals in the environment.

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.

Antioxidative responses of the tissues of two wild populations of Pelophylax kl. esculentus frogs to heavy metal pollution.

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.

Bioaccumulation and effects of metals on oxidative stress and neurotoxicity parameters in the frogs from the Pelophylax esculentus complex.

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.

Essential trace element levels in multiple sclerosis: Bridging demographic and clinical gaps, assessing the need for supplementation.

BACKGROUND: Multiple sclerosis (MS) is a chronic demyelinating disorder intricately linked to perturbations in trace element levels. While previous studies have explored circulating trace elements in a limited sample, understanding the impact of demographic and clinical variables on the elemental profile within a larger cohort remains elusive. METHODS: This study aimed to evaluate essential trace elements (Cr, Mn, Co, Cu, Zn, and Se) in the sera of 215 MS patients compared to a meticulously matched control group of 100 individuals with similar gender and age. Our main objective was to identify potential variations in elemental profiles based on demographic and clinical parameters among MS patients, elucidating the prospective relevance of supplementing specific essential trace elements. RESULTS: Data indicated a significant decrease in serum levels of Mn, Co, Zn, and Se, and an increase in Cr in MS patients compared to controls. These trace elements not only discriminated between MS patients and controls but also exhibited distinctive capabilities among demographic subgroups. Gender, smoking habits, and age strata (20-40 years and 41-60 years) revealed discernible variations in elemental profiles between MS patients and their control counterparts. Se demonstrated the singular ability to stratify cases of extreme MS severity, mild relapsing-remitting MS (RRMS) and highly severe secondary progressive MS (SPMS). In contrast, Co significantly differentiated RRMS from primary progressive MS (PPMS), while Cu significantly differentiated SPMS from PPMS. Additionally, Cu showed a negative correlation with MSSS, while Mn and Zn showed a positive correlation with EDSS. CONCLUSION: These findings underscore a substantive deficiency in Mn, Co, Zn, and Se in the MS cohort, supporting targeted supplementation with these trace elements. This study provides a comprehensive understanding of the intricate relationship between essential trace elements and MS, paving the way for further research into personalized nutritional interventions for this complex neurological disorder.

Does Lead Have a Connection to Autism? A Systematic Review and Meta-Analysis.

Environmental pollutants, particularly toxic trace metals with neurotoxic potential, have been related to the genesis of autism. One of these metals that stands out, in particular, is lead (Pb). We conducted an in-depth systematic review and meta-analysis of peer-reviewed studies on Pb levels in biological materials retrieved from autistic children (cases) and neurotypical children (controls) in this work. A systematic review was conducted after the careful selection of published studies according to established criteria to gain a broad insight into the higher or lower levels of Pb in the biological materials of cases and controls, and the findings were then strengthened by a meta-analysis. The meta-analysis included 17 studies (hair), 13 studies (whole blood), and 8 studies (urine). The overall number of controls/cases was 869/915 (hair), 670/755 (whole blood), and 344/373 (urine). This meta-analysis showed significantly higher Pb levels in all three types of biological material in cases than in controls, suggesting a higher body Pb burden in autistic children. Thus, environmental Pb exposure could be related to the genesis of autism. Since no level of Pb can be considered safe, the data from this study undoubtedly point to the importance of regularly monitoring Pb levels in autistic children.

Mercury and Autism Spectrum Disorder: Exploring the Link through Comprehensive Review and Meta-Analysis.

Mercury (Hg) is a non-essential trace metal with unique neurochemical properties and harmful effects on the central nervous system. In this study, we present a comprehensive review and meta-analysis of peer-reviewed research encompassing five crucial clinical matrices: hair, whole blood, plasma, red blood cells (RBCs), and urine. We assess the disparities in Hg levels between gender- and age-matched neurotypical children (controls) and children diagnosed with autism spectrum disorder (ASD) (cases). After applying rigorous selection criteria, we incorporated a total of 60 case-control studies into our meta-analysis. These studies comprised 25 investigations of Hg levels in hair (controls/cases: 1134/1361), 15 in whole blood (controls/cases: 1019/1345), 6 in plasma (controls/cases: 224/263), 5 in RBCs (controls/cases: 215/293), and 9 in urine (controls/cases: 399/623). This meta-analysis did not include the data of ASD children who received chelation therapy. Our meta-analysis revealed no statistically significant differences in Hg levels in hair and urine between ASD cases and controls. In whole blood, plasma, and RBCs, Hg levels were significantly higher in ASD cases compared to their neurotypical counterparts. This indicates that ASD children could exhibit reduced detoxification capacity for Hg and impaired mechanisms for Hg excretion from their bodies. This underscores the detrimental role of Hg in ASD and underscores the critical importance of monitoring Hg levels in ASD children, particularly in early childhood. These findings emphasize the pressing need for global initiatives aimed at minimizing Hg exposure, thus highlighting the critical intersection of human-environment interaction and neurodevelopment health.

Age-related changes in antioxidant defenses of the Mediterranean centipede Scolopendra cingulata (Chilopoda).

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.

Differences between antioxidant defense parameters and specific trace element concentrations in healthy, benign, and malignant brain tissues.

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.

The effects of meldonium on the acute ischemia/reperfusion liver injury in rats.

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.

Association between oxidative stress biomarkers and concentrations of some metal ions in the blood of patients with brain tumors and hydrocephalus.

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.

The protective role of virgin coconut oil on the alloxan-induced oxidative stress in the liver, kidneys and heart of diabetic rats.

The aim of this study was to investigate the potential protective effect of virgin coconut oil (VCO) on oxidative stress parameters in the liver, kidneys and heart of alloxan-induced (150 mg kg-1 i.p.-1) diabetes in rats. Our results showed that daily supplementation of VCO (20% of food) for 16 weeks significantly (p < 0.05) ameliorates some deleterious effects caused by alloxan. VCO reduced the diabetes-related increase in food (82.15 ± 1.49 vs. 145.51 ± 4.81 g per kg b.m. per day) and water (305.49 ± 6.09 vs. 583.98 ± 14.80 mL per kg b.m. per day) intake, and the decrease in the body mass gain (0.56 ± 0.16 vs. -2.13 ± 0.49 g per 100 g b.m. per week). In all three tissues, diabetes caused an increase in the concentration of total glutathione and sulfhydryl groups, and catalase and glutathione S-transferase activities, without changes in superoxide dismutase activity. Glutathione peroxidase activity was increased in the kidneys and heart, but not in the liver of the diabetic animals, while glutathione reductase activity was increased in the liver and the kidneys, and not in the heart. The simultaneous VCO supplementation increased the concentration of the sulfhydryl group in all three tissues of diabetic animals and decreased the glutathione S-transferase activity and glutathione concentration, without affecting the glutathione reductase activity. In the liver of diabetic animals it decreased superoxide dismutase, catalase and glutathione peroxidase activities, in the heart catalase and glutathione peroxidase activities, and in the kidney catalase activity only. The results of canonical discriminant analysis of oxidative stress parameters revealed that VCO exerts its effects in a tissue-specific manner.

Do different diets affect oxidative stress biomarkers and metal bioaccumulation in two snake species?

In this study we examined possible differences in heavy metal accumulation and oxidative stress parameters in the liver and muscle of two semi-aquatic snakes: grass snake (Natrix natrix) and dice snake (N. tessellata), that inhabit the same environment but differ in prey diversity. The obtained results revealed some interspecies, inter-tissue, prey-snake and prey-prey differences in heavy metal concentrations. Grass snakes pray contained significantly higher concentrations of Al, Cr and Fe as compared to food of dice snakes. Both investigated snakes accumulated generally lower concentrations of metals than their prey, indicating that they are not at risk of contaminant biomagnification. A significant interspecies difference in accumulation was observed only for Cu and Mn concentrations. On the other hand, analysis of oxidative stress biomarkers showed clear differences between the investigated snake species and the two investigated tissues. The liver of grass snake had increased superoxide dismutase, glutathione reductase and glutathione-S-transferase activities in comparison to dice snake. In muscle, a reverse trend was observed for the activities of these three enzymes, as well as for glutathione peroxidase activity. The higher number of significant correlations observed between oxidative stress biomarkers and heavy metal concentrations in grass snake points to upregulation of the antioxidative system (AOS), which resulted in a lower TBARS concentration. Results show that while the investigated snake species did not differ significantly in the accumulated metals, their defense mechanisms were different. This reveals the complexity of the AOS and points to the cooperation of different AOS components in individuals from natural populations.