Search Results (146)

Estuarine and river-influenced coastal ecosystems are recognized as important sinks and channels for transfer of heavy metals into the marine environment. Continuous intake of metal pollutants could create chronic exposure situations, perhaps leading to molecular and cellular damage to resident biota, even if environmental concentrations are within regulatory limits. Thus, the incorporation of molecular and genotoxicity biomarkers into environmental monitoring programs has received growing interest, as changes in gene expression are among the earliest detectable responses to pollutant stress and may precede genotoxic effects, including DNA damage, at higher or prolonged levels of contaminant exposure. The present study aimed to determine the levels of heavy metals in the coastal zone where the Deliçay River flows into the Gulf of Iskenderun in the extreme northeastern Mediterranean Sea, Türkiye, and to investigate the genotoxic effects in the euryhaline ray-finned fish golden grey mullet (Chelon auratus). In this study, seasonal water samples (n = 3 per site per season) and C. auratus specimens (n = 10 per site per season; total n = 80) were collected from a reference site and the Deliçay estuary. Water samples were analyzed for metals (cadmium (Cd), chromium (Cr), iron (Fe), lead (Pb), and zinc (Zn)) and fish samples were analyzed with the micronucleus (MN) test for determining nuclear abnormalities and the comet test for DNA damage levels. The concentrations of Fe, Zn, and Pb in seawater exceeded the Criterion Continuous Concentration (CCC) thresholds during the summer and autumn seasons, as well as in terms of annual mean values, indicating a potential chronic ecological risk to marine organisms. From the results of the micronucleus test performed in the present study, the highest MN frequencies (10.16 ± 0.15%) and other erythrocytic nuclear anomalies [kidney-shaped (10.36 ± 0.32%), binucleated (14.20 ± 0.10%), notched (14.63 ± 0.20%), lobed (15.43 ± 0.11%), and budded (15.33 ± 0.15%)] were found along the studied coastal zone in summer season. Results of the comet test, supporting the micronucleus test results, showed the highest percentages of DNA damage determined in all seasons in the gill and liver tissues of fish sampled in the studied coastal zone. This study is the first to evaluate the effects of heavy metal-induced genotoxic stress on ecological integrity in this coastal zone using a biomarker-based approach, and the results underscore the need for comprehensive environmental monitoring and pollution reduction strategies to protect ecosystem health. Full article

Nanoparticles combining gold and iron oxide are promising for a wide range of biomedical applications, including photothermal therapy, radiotherapy enhancement, drug delivery, and diagnostic imaging. However, their long-term biodistribution and safety profile remain largely unexplored. Here, we synthesized Fe₃O₄@AuNP core–satellite nanoparticles (Fe₃O₄@AuNPs) using femtosecond laser ablation, functionalized them with 15 kDa polyethylene glycol (PEG), and characterized them using a panel of physicochemical techniques. Healthy C57BL/6 mice received an intravenous injection of Fe₃O₄@AuNPs at 730 mg Au/kg and 82 mg Fe/kg, respectively. Biodistribution was monitored by computed tomography (CT) and magnetic resonance imaging (MRI) over 12 months, after which gold and iron concentrations were measured ex vivo, and long-term toxicity was assessed via histology and blood biochemistry. Nanoparticles accumulated predominantly in the liver and spleen. Quantitative analysis of CT images revealed a gradual decrease in gold content, while MRI showed a progressive reduction in negative contrast in the liver between 6 and 12 months, suggesting possible changes in the Fe₃O₄ core structure. Over the one-year observation period, no differences in behavior or body weight gain were detected between the treated and control groups. Histological examination revealed no pathological changes other than mild age-related alterations. These findings provide a baseline for the long-term behavior of laser-ablated core–satellite Fe₃O₄@AuNPs, which is essential for their further development in diagnostic and theranostic applications. Full article

Freshwater ecosystems are increasingly exposed to metal contamination arising from natural and anthropogenic activities, potentially affecting fish physiology and ecosystem health. However, limited information is available regarding metal accumulation and associated biological responses in fish populations from Dukan Lake, northern Iraq. Therefore, this study investigated metal concentrations in water and tissues of common carp (Cyprinus carpio) and evaluated their relationships with selected fish health indicators. Water and fish samples were collected monthly from Dukan Lake, and a total of 60 fish were classified into three length groups (20–29 cm, 30–39 cm, and 40–49 cm). Metal concentrations in water, liver, and gonad tissues were analyzed using ICP-OES, while condition factor (CF), gonadosomatic index (GSI), and hepatosomatic index (HSI) were used to assess fish physiological condition. Sodium (Na), magnesium (Mg), potassium (K), iron (Fe), zinc (Zn), and barium (Ba) were detected in both water and fish tissues, with concentrations in water ranging from 50 to 7069 μg/L. In contrast, chromium (Cr), manganese (Mn), nickel (Ni), selenium (Se), silver (Ag), cadmium (Cd), antimony (Sb), lead (Pb), copper (Cu), and arsenic (As) were below detection limits. Biometric analysis revealed significant differences (p < 0.05) in the gonadosomatic index (GSI) among fish length groups, indicating size-dependent reproductive development. However, no significant relationship was observed between fish length and either the CF or HSI, suggesting relatively stable somatic condition or liver status across size classes. Correlation analysis showed no significant associations between water metal concentrations and CF or GSI. A significant positive correlation was identified between Zn concentration and HSI in the 30–39 cm length group, indicating a possible link between Zn exposure and hepatic physiological response. The findings indicate that essential elements dominate the metal profile in Dukan Lake, with limited evidence of toxic metal contamination. No major adverse effects on the general condition of the fish were observed. These results contribute to understanding metal bioaccumulation patterns and their implications for fish health in freshwater ecosystems. Full article

Background/Objectives: Accurate liver iron content (LIC) quantification and monitoring are crucial for managing patients with hematological disorders. Biopsy-based LIC assessment is invasive and prone to sampling errors. This study aimed to develop a simple and safe method for calibrating MR scanner to accurately measure LIC. Methods: Five certified test objects with increasing aqueous Fe³⁺ solutions were used for R2* relaxometry to create a calibration curve with equation for converting R2* value to iron content (mg/g), using two different MR scanners. Additionally, two sets of test objects (aqueous and gelled solutions to mimic liver tissue) were developed to evaluate the feasibility of using homemade test objects. Our method was compared with two existing methods (Wood et al.’s equation and the Iron Calculator App) in 59 hematological patients, using the certified test object method as reference. We also compared our method with biopsy-based iron quantification (inductively coupled plasma optical emission spectroscopy) in four patients. Results: The equations derived from our homemade test objects were comparable to those from certified test objects across both MRI scanners. The literature methods consistently overestimated LIC compared to our method. For biopsy validation, our method was more accurate in two out of four cases. Conclusions: Our homemade calibration method offers a simple, reliable alternative for LIC quantification. The type of test object (aqueous or gelled) showed no significant difference. While biopsy-based methods remain useful, our MRI-based approach is quicker and avoids the limitations of biopsy sampling. This method, relying on the relationship between iron concentrations and relaxation times, could provide a more comprehensive and accurate assessment of liver iron levels. Full article

Background/Objectives: Red beetroot (Beta vulgaris L.) is recognized for its antioxidant, anti-inflammatory, and metabolic properties. This study evaluated the effects of two beetroot cultivars (Boldor and Wodan) on blood serum parameters, body composition, and organ weights in male WKY rats fed a low-protein diet (LPD, 8.8% protein). Methods: Five-week-old male rats were maintained on an LPD for 8 weeks and subsequently continued on the LPD diet supplemented with 4% dried beetroot for 45 days. The experimental diets included beetroot from the Boldor and Wodan cultivars, either treated or untreated with a plant growth stimulator during cultivation. Results: Foliar application of the selenium-based plant growth stimulator did not significantly increase selenium or other element concentrations in beet roots. Elemental analysis showed higher levels of Fe, Zn, Cu, Cr, Pb, As, Cd, and Sb in the Wodan group, while Boldor increased Cr, Pb, and As; Ni and Se remained unchanged. Beetroot supplementation significantly affected 14 of the 30 measured biochemical parameters, including biomarkers of liver function (ALT, ALP, total bilirubin, albumin, and total protein), renal function (uric acid), pancreatic activity (amylase and lipase), electrolyte balance (sodium, potassium, and chloride), mineral metabolism (calcium), inflammatory status (CRP), and nutritional metabolism (iron). Conversely, no significant effects were observed on lipid profile parameters or biomarkers of cardiac and skeletal muscle injury. Among the beetroot cultivars evaluated, Wodan exerted distinct effects relative to Boldor, resulting in higher circulating total bilirubin and potassium concentrations, alongside reduced uric acid and lipase levels in treated rats. Boldor supplementation significantly increased body weight gain and fat mass, with a trend toward higher lean mass, and increased kidney weight. Wodan did not significantly affect body weight but increased kidney and spleen mass. Feed intake was similar across groups. No changes in cardiovascular function were observed ex vivo. Conclusions: Beetroot supplementation modulated multiple metabolic and physiological biomarkers in rats fed a low-protein diet, with distinct cultivar-specific effects, underscoring the importance of cultivar selection for optimizing functional dietary interventions. Full article

Alcohol-related liver disease (ALD) and ALD-related mortality are associated with hemolysis, increased erythrophagocytosis, and disturbed iron homeostasis. While macrophage-mediated erythrophagocytosis is well established, we investigated the contribution of liver sinusoidal endothelial cells (LSECs) to handling oxidatively damaged or ethanol-primed red blood cells (RBCs) in ALD. Live-cell imaging demonstrated that damaged RBCs were rapidly taken up by SK-HEP1 cells, an endothelial cell line with LSEC-like characteristics, and RBC uptake was associated with induction of heme oxygenase-1 (HO-1) and activation of its upstream regulator Nrf2. siRNA-mediated knockdown of the scavenger receptor Stabilin-1 attenuated RBC-induced HO-1 expression, supporting a role for Stabilin-1 in efferocytic signaling. Exposure of RBCs to ethanol concentrations as low as 25 mM induced phosphatidylserine externalization and rendered erythrocytes efferocytosis-competent. Lysed RBCs and free hemin elicited comparable oxidative stress responses. In murine models of hemolysis and chronic ethanol feeding, hemoglobin-derived signals were detected within sinusoidal structures showing a diffuse CD206-positive distribution pattern consistent with the sinusoidal scavenger compartment. Similar signals were observed in sinusoidal endothelial regions in human heavy drinkers with clinical signs of hemolysis. Together, these data suggest that LSECs may represent an additional component of RBC clearance in ALD, alongside macrophages and hepatocytes, with implications for hepatic iron handling. Full article

Fish oil (FO) has been shown to confer beneficial effects on hepatic diseases in both humans and animals. This study aimed to investigate whether dietary fish oil (FO) supplementation alleviates deoxynivalenol (DON)-induced liver injury by modulating the ferroptosis signaling pathway in weaned piglets. Twenty-four weaned piglets were allocated to a 2 × 2 factorial design, with the main factors consisting of dietary treatment (5% corn oil or 5% FO supplementation) and DON exposure (basal diet or diet contaminated with 4 mg/kg DON). After 21 days of dietary treatment, piglets were euthanized for collection of blood and liver samples. Dietary FO significantly attenuated DON-induced hepatic structural damage and inflammatory infiltration. Specifically, FO supplementation reduced the activities of aspartate transaminase (AST) and alkaline phosphatase (ALP), as well as the AST/alanine aminotransferase (ALT) ratio following DON exposure. Dietary FO also decreased malondialdehyde (MDA) concentrations in both the liver and serum, lowered hepatic 4-hydroxynonenal (4-HNE) level and Fe²⁺ content, and increased hepatic glutathione (GSH) content. Moreover, dietary FO ameliorated ultrastructural liver damage induced by DON. Furthermore, DON significantly downregulated the mRNA levels of multiple genes associated with iron metabolism and ferroptosis, including heat shock protein beta-1 (HSPB1), acyl-CoA synthetase long chain family member 4 (ACSL4), and arachidonate 15-lipoxygenase (ALOX15), and upregulated the mRNA levels of transferrin (TF), ferritin heavy chain (FTH), solute carrier family 7 member 11 (SLC7A11), and transferrin receptor 1 (TFR1). Dietary FO counteracted these alterations by decreasing the mRNA of SLC7A11, TFR1, FTH, and TF after DON exposure. Finally, FO significantly decreased the protein expression of SLC7A11, iron-responsive element-binding protein 2 (IREB2), and FHT1 and increased the GPX4 protein expression following DON exposure. These findings suggest that FO may ameliorate DON-induced liver injury in weaned piglets, possibly through suppressing the ferroptosis signaling pathway. Full article

The dose–response relationship for fluoride (F⁻) exposure remains largely unexplored. Hence, the current study assessed the hepatotoxic and nephrotoxic effects of subacute exposure (28 days) to increasing F⁻ concentrations in Wistar rats via the benchmark dose (BMD5) method. Thirty male rats were assigned to six groups (n = 5): a control group (tap water) along with five groups that received F⁻ via drinking water at increasing concentrations (10, 25, 50, 100, and 150 mg/L). F⁻ toxicity was determined via water intake, weight gain, histological analyses, redox status, and essential element levels. PROASTweb 70.1 software was utilized to investigate the external and internal F⁻ dose–response relationships. Specified major cytoarchitecture damage and superoxide anion (O₂·⁻), total oxidative status (TOS), superoxide dismutase (SOD) activity, total thiol groups (SH), and advanced oxidation protein product (AOPP) level alterations were detected in both sets of tissues. Moreover, F⁻ caused an imbalance in copper (Cu), zinc (Zn), iron (Fe), and manganese (Mn). The most sensitive parameters were O₂·⁻ (0.06 mg F⁻/kg) in the liver and AOPP (6.5 × 10⁻⁶ mg F⁻/L) in the kidneys. These findings contribute to the limited risk assessment of fluorides and highlight the dose-dependent relationship between redox status parameters and bioelements in the liver and kidneys. Full article

Background/Objectives: Oxidative stress and iron overload remodel erythrocyte membranes in β-thalassemia, but their systemic metabolic correlates are not well defined. We applied untargeted metabolomics to identify serum biomarkers reflecting these pathophysiological processes. Methods: Thirty-one adults with β-thalassemia [18 transfusion-dependent (TDT), 13 non-transfusion-dependent (NTD)] and 8 age/sex-matched healthy controls were studied. Fasting serum was profiled using untargeted UHPLC–Orbitrap MS. Multivariate modeling (SIMCA-P) and FDR-controlled univariate statistics identified discriminant features, followed by pathway enrichment analysis. Associations with clinical variables (chelation regimen, ferritin, cardiac MRI T2*, and liver iron concentration) were examined. Results: A total of 183 metabolites were detected; versus controls, 124 were decreased, 54 increased, and 5 remained unchanged in patients. Key discriminants included lysophosphatidylcholines (LysoPC 18:1, 18:3), polyunsaturated fatty acid (PUFA)-bearing phosphatidylcholines (PC 20:4/18:0, PC 18:0/20:4), conjugated bile acids (glycocholic acid, glycochenodeoxycholic acid, and glycoursodeoxycholic acid), and bilirubin. Pathway analysis revealed significant enrichment (FDR-corrected) in linoleic acid metabolism (q = 0.024, impact = 1.000) and arachidonic acid metabolism (q = 0.022, impact = 0.433), with supportive nominal signals from glycerophospholipid (impact = 0.401) and porphyrin/heme (impact = 0.242) pathways. No significant metabolic differences were observed between TD and NTD patients. Conclusions: β-thalassemia serum metabolomics reflects oxidative membrane lipid remodeling with a prominent PLA₂/LysoPC–arachidonic axis and evidence of heme turnover and altered bile-acid signaling. These data propose a practical biomarker panel-LysoPCs, arachidonic acid-enriched PCs, and conjugated bile acids-warranting targeted validation alongside conventional clinical parameters for disease monitoring and therapeutic assessment. Full article

Lead (Pb) has progressively become ubiquitous due to widespread use. The liver represents a target of Pb toxicity due to its central role in metabolism and detoxification. The mechanisms of Pb hepatotoxicity have not yet been fully elucidated, although oxidative stress and iron dysregulation suggest the involvement of the ferroptosis pathway. It has been hypothesized that exposure to environmental Pb concentrations induces the activation of ferroptosis as a mechanism involved in Pb hepatotoxicity, an iron-mediated regulated cell death. To test this hypothesis, we exposed adult zebrafish to environmentally relevant Pb concentrations (2.5 and 5 μg/L), combining ultrastructural analysis (TEM) with the study of key markers of ferroptosis (GPX4, SLC7A11, NRF2, KEAP1 and ACSL4). The results demonstrated that Pb exposure induced dose-dependent and progressive mitochondrial damage in hepatocytes, characterized by loss of cristae and membrane rupture. At the same time, consistent with a ferroptotic molecular profile, increased expression of ACSL4, reduced levels of the protective factors NRF2, KEAP1 and SLC7A11, and altered expression of GPX4 were observed. Overall, our data collectively identify ferroptosis as a pathogenic pathway in Pb-induced hepatotoxicity. Full article

Background: Commercial feed formulations are increasingly being evaluated for their nutritional impacts on aquaculture species, yet the molecular consequences of commonly used commercial diets remain underexplored. Methods: This study investigated the effects of two commercial diets, diet A (higher land animal protein) and diet B (higher fish meal content), on the protein profile in the brain, liver, and intestine of barramundi (Lates calcarifer). A 12-week feeding trial was conducted with controlled water quality, and proteomic profiling was performed using data-independent acquisition. Results: Differential analysis revealed consistent changes between diets across all tissues, with a higher percentage of differentially abundant proteins observed in between-diet comparisons (12.99% in brain, 12.73% in liver, and 16.59% in intestine) than within-diet controls (<8%), confirming a measurable dietary effect size. In total, 3901 proteins in the brain, 3660 in the liver, and 5025 in the intestine were quantified. Functional enrichment highlighted upregulation of ferroptosis pathways, downregulation of apelin signaling in the brain, and increased digestive proteases in the liver. ICP-MS confirmed elevated iron concentrations in the brain, liver, and intestine of fish fed on diet B. Conclusions: These findings demonstrate that molecular pathways linked to iron metabolism, digestion, and growth regulation are very sensitive to dietary composition, highlighting how proteomics can help identify subtle impacts of compositional differences in aquaculture feeding. Although physiological parameters did not differ significantly, the proteomic alterations observed across tissues likely indicate organ-specific metabolic adaptations to the differing nutrient availability between diets. Full article

In this study, we investigated the bioaccumulation of 17 heavy metals—titanium, vanadium, chromium, manganese, iron, cobalt, nickel, copper, zinc, arsenic, selenium, molybdenum, antimony, cadmium, tin, mercury, and lead—in the liver and kidney tissues of the least weasel, based on samples (n = 129) collected from adjacent intensive agricultural environments in Hungary and Austria. To explore the structure of the bioaccumulation data, principal component analysis (PCA) was performed. The PCA score plot based on national-level elemental profiles revealed no differentiation between Austria and Hungary. In contrast, a clear and unambiguous distinction was observed between the two examined tissues within individuals for Ti, Mn, Fe, Co, Zn, Se, Mo, Cd, and Hg (p < 0.001), as well as for Pb (p < 0.05). The biological relevance of the accumulation results was adjusted using the MCID approach. As heavy metal accumulation in the least weasel has not yet been investigated, our results could only be compared with concentrations reported for predatory mammals occurring in similar habitats. Based on the relevant literature, we highlight predominantly anthropogenic exposure pathways affecting agroecosystems—organic and mineral fertilizers, plant protection products, wastewater, and fossil fuels—which underscore the necessity of regular biomonitoring studies in agricultural landscapes. Full article

Despite manganese’s essential role as a cofactor for multiple enzymes, its potential to disrupt iron homeostasis when supplemented in excess remains a critical knowledge gap in swine nutrition. This study evaluated the effects of Mn (manganese)-supplemented diets on growth, hematology, mineral accumulation, digestibility, and intestinal iron transporter expression in weaned pigs. A total of 128 crossbred pigs (Duroc × Landrace × Largewhite) with an average body weight of 9.82 ± 0.15 kg were randomly allotted to four dietary treatments comprising a basal diet supplemented with 0, 20, 40, or 80 mg MnSO₄ per kg diet for 28 days. Blood samples were collected from 16 weaned pigs (1 pig per pen, 4 per treatment), after which animals were euthanized for tissue sampling. No differences were observed in growth performance. However, Mn concentrations in serum, liver, heart, kidney, pancreas, and metatarsal bones increased both linearly and quadratically with increasing dietary Mn (p < 0.05), and Fe (iron) concentrations in serum, hemoglobin, liver, and metatarsal bone decreased (p < 0.05). Apparent digestibility data further revealed that Mn absorption peaked at 20 mg/kg, while Fe digestibility declined linearly with increasing Mn levels. Moreover, duodenal DMT1 (divalent metal transporter 1) mRNA expression was decreased, whereas FPN1 (ferroportin 1) was upregulated. These findings demonstrate that excessive Mn supplementation impairs dietary Fe absorption and homeostasis in weaned pigs, suggesting that the antagonism occurs at both the transcriptional and intestinal absorption levels, providing critical insights for dietary formulation in swine. Full article

This study evaluated whether iron supplementation in the form of chelated minerals in cows in the final third of lactation has a positive effect on iron bioavailability, immunity, oxidative status, milk quality, and biochemical and hematological parameters, as well as production efficiency and fecal microbiota. Twenty-four multiparous Jersey cows, with 210 ± 18 days in milk (DIM), an average production of 25 kg, and 4 ± 0.6 months of gestation, were divided into two groups: Control (n = 12, without supplementation) and Iron (n = 12, supplemented with 30 mg of iron/kg of dry matter (600 mg/animal/day)). Blood and milk samples were collected on days 1, 16, 29, and 42 of the experiment. Supplemented animals had higher serum iron concentrations and a higher unsaturated iron-binding capacity, especially on day 42. Higher iron content in milk was also observed. A higher granulocyte count was observed in the iron group, as well as a lower number of lymphocytes compared to the control, which may indicate immunosuppression associated with iron supplementation. Fructosamine levels were significantly lower in the iron group animals on days 14 and 28, suggesting a possible alteration in glucose metabolism. In contrast, levels of the liver enzymes AST and ALT increased significantly in the group supplemented with iron on days 28 and 42, indicating potential liver overload or injury. Iron supplementation significantly increased levels of reactive oxygen species and thiobarbituric acid-reactive substances, as well as superoxide dismutase activity in the blood. Iron supplementation altered gut microbial diversity, promoting dysbiosis characterized by increased alpha diversity and enrichment of transient colonization by Nitratireductor, Brevundimonas, Flavobacterium and Sporosarcina. Lower milk production was observed in the iron-supplemented cows in the last 10 days of the experiment, which is related to the occurrence of disease in nine cows in this group: seven with mastitis and two with intestinal peristalsis paralysis. Based on these results, we conclude that chelated iron supplementation at a dose of 600 mg/animal/day should not be used because it harms cow health and productivity. Full article

Analgesia, or reduced pain sensitivity, can result from pharmacological or stress-induced mechanisms, but human studies are limited by complex physiological and psychological variables. This study aimed to evaluate the impact of ethanol consumption on key metabolic markers in two genetically distinct mouse lines selectively bred for pain sensitivity: high analgesia (HA) and low analgesia (LA). Forty-eight male Swiss-Webster mice were randomly assigned to four groups: HA and LA with or without heavy alcohol (ethanol) exposure. Blood serum was analyzed for its lipid profile, enzymatic activity, electrolyte levels and regulatory/energetic compounds. In HA mice, ALAT and AspAT activities and, albumin, creatinine, iron, and potassium levels were elevated, whereas glucose and sodium levels were decreased. LA mice presented increased bilirubin, cholesterol, LDL, HDL, and lipase activity. ChE, LDH, and CK activities differed significantly between the HA and LA groups. Ethanol intake influenced potassium, magnesium, and sodium serum concentrations. Discriminant analysis highlighted distinct biochemical profiles depending on the LA and HA groups. HA mice predominantly exhibit cytolytic liver damage, altered muscle metabolism, and increased iron levels, indicating oxidative stress. HA and LA display distinct adaptive metabolic strategies: protein/muscle and lipid/electrolyte metabolism, respectively. Genetic differences between HA and LA mice determine different metabolic responses to ethanol. Full article