Search Results (13)

Background: Previous studies have highlighted that copper supplementation at 200% of the recommended daily dietary allowance modified vascular contraction and relaxation through increased reactive oxygen species (ROS) and prostaglandin formation, which modified the antioxidant status of middle-aged Wistar rats. Methods: In this study, young (1 month old) male Wistar rats (n/group = 10) received a diet supplemented with 6.45 mg copper/kg (100% of daily recommendation—Group A) for 8 weeks. The experimental group received 12.9 mg copper/kg of diet (200% of the daily recommendation—Group B). Results: Experimental supplementation with 200% copper modified the copper concentration in the blood (1.21-fold, p = 0.04), liver (1.15-fold, p = 0.032), and kidneys (1.23-fold, p = 0.045), potentiated the ROS formation in the aortic rings, and enhanced the sensitivity of the aortic rings to the vasodilator acetylcholine. We observed an increased participation of nitric oxide (NO) derived from inducible NO synthase (iNOS) in vascular contraction and a decreased net effect of vasodilator prostanoids derived from cyclooxygenase-2 in vascular relaxation. In rat kidneys, the concentrations of potassium (1.08-fold, p = 0.001) and iron (1.13-fold, p = 0.046) were higher, while, calcium (0.88-fold, p = 0.001) and chromium (0.77-fold, p = 0.005) concentrations were lower. In the rat liver, magnesium (1.06-fold, p = 0.012) was higher. No differences were observed in the concentrations of sodium, zinc, manganese, selenium, cobalt, molybdenum, and vanadium. The antioxidant activity of water- and lipid-soluble compounds; total antioxidant status in the blood; and superoxide dismutase, catalase, and malondialdehyde levels in the heart did not change. Conclusions: In young rats, prolonged supplementation with 200% copper had a lesser effect than anticipated on oxidative stress and vascular reactivity. Detailed data on the status of trace elements and their interactions in patients of different age groups are strongly required for effective nutritional and therapeutic intervention. Full article

Peripheral nerve damage that results in lost segments requires surgery, but currently available hollow scaffolds have limitations that could be overcome by adding internal guidance support. A novel solution is to use filaments of absorbable metals to supply physical support and guidance for nerve regeneration that then safely disappear from the body. Previously, we showed that thin filaments of magnesium metal (Mg) would support nerve regeneration. Here, we tested another absorbable metal, zinc (Zn), using a proprietary zinc alloy with 2% iron (Zn-2%Fe) that was designed to overcome the limitations of both Mg and pure Zn metal. Non-critical-sized gaps in adult rat sciatic nerves were repaired with silicone conduits plus single filaments of Zn-2%Fe, Mg, or no metal, with autografts as controls. After seventeen weeks, all groups showed equal recovery of function and axonal density at the distal end of the conduit. The Zn alloy group showed some improvements in early rat health and recovery of function. The alloy had a greater local accumulation of degradation products and inflammatory cells than Mg; however, both metals had an equally thin capsule (no difference in tissue irritation) and no toxicity or inflammation in neighboring nerve tissues. Therefore, Zn-2%Fe, like Mg, is biocompatible and has great potential for use in nervous tissue regeneration and repair. Full article

High oxygen concentrations are often required to treat newborn infants with respiratory distress but have adverse effects, such as increased oxidative stress and ferroptosis and impaired alveolarization. Cathelicidins are a family of antimicrobial peptides that exhibit antioxidant activity, and they can reduce hyperoxia-induced oxidative stress. This study evaluated the effects of cathelicidin treatment on lung ferroptosis and alveolarization in hyperoxia-exposed newborn rats. Sprague Dawley rat pups were either reared in room air (RA) or hyperoxia (85% O₂) and then randomly given cathelicidin (8 mg/kg) in 0.05 mL of normal saline (NS), or NS was administered intraperitoneally on postnatal days from 1–6. The four groups obtained were as follows: RA + NS, RA + cathelicidin, O₂ + NS, and O₂ + cathelicidin. On postnatal day 7, lungs were harvested for histological, biochemical, and Western blot analyses. The rats nurtured in hyperoxia and treated with NS exhibited significantly lower body weight and cathelicidin expression, higher Fe²⁺, malondialdehyde, iron deposition, mitochondrial damage (TOMM20), and interleukin-1β (IL-1β), and significantly lower glutathione, glutathione peroxidase 4, and radial alveolar count (RAC) compared to the rats kept in RA and treated with NS or cathelicidin. Cathelicidin treatment mitigated hyperoxia-induced lung injury, as demonstrated by higher RAC and lower TOMM20 and IL-1β levels. The attenuation of lung injury was accompanied by decreased ferroptosis. These findings indicated that cathelicidin mitigated hyperoxia-induced lung injury in the rats, most likely by inhibiting ferroptosis. Full article

Anemia is a commonly observed consequence of whole-body exposure to a dose of X-ray or gamma irradiation of the order of the mean lethal dose in mammals, and it is an important factor for the determination of the survival of animals. The aim of this study was to unravel the effect of laser-driven ultrashort pulsed electron beam (UPEB) irradiation on the process of erythropoiesis and the redox state in the organism. Wistar rats were exposed to laser-driven UPEB irradiation, after which the level of oxidative stress and the activities of different antioxidant enzymes, as well as blood smears, bone marrow imprints and sections, erythroblastic islets, hemoglobin and hematocrit, hepatic iron, DNA, and erythropoietin levels, were assessed on the 1st, 3rd, 7th, 14th, and 28th days after irradiation. Despite the fact that laser-driven UPEB irradiation requires quite low doses and repetition rates to achieve the LD₅₀ in rats, our findings suggest that whole-body exposure with this new type of irradiation causes relatively mild anemia in rats, with subsequent fast recovery up to the 28th day. Moreover, this novel type of irradiation causes highly intense processes of oxidative stress, which, despite being relatively extinguished, did not reach the physiologically stable level even at the 28th day after irradiation due to the violations in the antioxidant system of the organism. Full article

When exposed to an alternating magnetic field, superparamagnetic nanoparticles can elicit the required hyperthermic effect while also being excellent magnetic resonance imaging (MRI) contrast agents. Their main drawback is that they diffuse out of the area of interest in one or two days, thus preventing a continuous application during the typical several-cycle multi-week treatment. To solve this issue, our aim was to synthesise an implantable, biodegradable membrane infused with magnetite that enabled long-term treatment while having adequate MRI contrast and hyperthermic capabilities. To immobilise the nanoparticles inside the scaffold, they were synthesised inside hydrogel fibres. First, polysuccinimide (PSI) fibres were produced by electrospinning and crosslinked, and then, magnetitc iron oxide nanoparticles (MIONs) were synthesised inside and in-between the fibres of the hydrogel membranes with the well-known co-precipitation method. The attenuated total reflectance Fourier-transform infrared spectroscopy (ATR-FTIR) investigation proved the success of the chemical synthesis and the presence of iron oxide, and the superconducting quantum interference device (SQUID) study revealed their superparamagnetic property. The magnetic hyperthermia efficiency of the samples was significant. The given alternating current (AC) magnetic field could induce a temperature rise of 5 °C (from 37 °C to 42 °C) in less than 2 min even for five quick heat-cool cycles or for five consecutive days without considerable heat generation loss in the samples. Short-term (1 day and 7 day) biocompatibility, biodegradability and MRI contrast capability were investigated in vivo on Wistar rats. The results showed excellent MRI contrast and minimal acute inflammation. Full article

Prenatal alcohol exposure causes neurodevelopmental disability and is associated with a functional iron deficiency in the fetus and neonate, even when the mother consumes an apparently iron-adequate diet. Here, we test whether gestational administration of the clinically relevant iron supplement Fer-In-Sol mitigates alcohol’s adverse impacts upon the fetus. Pregnant Long-Evans rats consumed an iron-adequate diet and received 5 g/kg alcohol by gavage for 7 days in late pregnancy. Concurrently, some mothers received 6 mg/kg oral iron. We measured maternal and fetal weights, hematology, tissue iron content, and oxidative damage on gestational day 20.5. Alcohol caused fetal anemia, decreased fetal body and brain weight, increased hepatic iron content, and modestly elevated hepatic malondialdehyde (p’s < 0.05). Supplemental iron normalized this brain weight reduction in alcohol-exposed males (p = 0.154) but not female littermates (p = 0.031). Iron also reversed the alcohol-induced fetal anemia and normalized both red blood cell numbers and hematocrit (p’s < 0.05). Iron had minimal adverse effects on the mother or fetus. These data show that gestational iron supplementation improves select fetal outcomes in prenatal alcohol exposure (PAE) including brain weight and hematology, suggesting that this may be a clinically feasible approach to improve prenatal iron status and fetal outcomes in alcohol-exposed pregnancies. Full article

High-voltage pulses applied to a cell suspension cause not only cell membrane permeabilization, but a variety of electrolysis reactions to also occur at the electrode–solution interfaces. Here, the cytotoxicity of a culture medium treated by a single electric pulse and the role of the iron ions in this cytotoxicity were studied in vitro. The experiments were carried out on mouse hepatoma MH-22A, rat glioma C6, and Chinese hamster ovary cells. The cell culture medium treated with a high-voltage pulse was highly cytotoxic. All cells died in the medium treated by a single electric pulse with a duration of 2 ms and an amplitude of just 0.2 kV/cm. The medium treated with a shorter pulse was less cytotoxic. The cell viability was inversely proportional to the amount of electric charge that flowed through the solution. The amount of iron ions released from the stainless steel anode (>0.5 mM) was enough to reduce cell viability. However, iron ions were not the sole reason of cell death. To kill all MH-22A and CHO cells, the concentration of Fe³⁺ ions in a medium of more than 2 mM was required. Full article

Currently, there is an objective need to create fortified food products that allow not only to provide the body with energy, but also to replenish the deficiency of essential nutrients. A generalization of the information published by Rospotrebnadzor and the Institute of Nutrition of the Russian Academy of Medical Sciences indicates a deficiency in the diet of Russians of vitamins C, group B and β-carotene and minerals, including calcium and iron, regardless of the season of the year. The identified deviations lead to a violation of the immune status, a decrease in the body’s resistance to infections, and other unfavorable environmental factors, leading to an increase in the level of morbidity and a decrease in working capacity. The main unfavorable climatic factor that the population of the Far Eastern region has to face is low freezing temperatures. Adaptation to cold exposure is a complex process that requires a long period and may be accompanied by functional disorders and morphological changes in body tissues. In connection with the above, the problem of increasing the adaptive capabilities of a person to unfavorable environmental factors by means of correcting daily nutrition, providing the body with essential macro- and micronutrients, which is important in the prevention of possible diseases, is of particular importance. This study is aimed at assessing the effect of Schisandrachinensis extract on the adaptive capacity of rats in conditions of chronic and general cold. It was found that the extracts obtained from the fruits of Schisandra chinensis are characterized by a high content of biologically active substances. In experiments with determining the duration of running on the treadmill, a distinct act-protective effect was observed with the introduction of Schisandra chinensis extracts at a dose of 150 mg/day, against the background of reduced resistance to physical activity due to cold exposure. It was found that exposure to cold significantly reduced the swimming resistance of rats on all days of the study. The introduction of Schisandra chinensis extract into the diet led to an increase in resistance to fatigue and an increase in the duration of swimming on all days of the experiment. Conclusions: in this experimental model, a gradually increasing effect of increasing the physical performance of rats was demonstrated with prolonged (28 days) intake of the developed drinks, which coincides with the literature data on a number of other adaptogens and indicates the presence of cumulative properties of biologically active substances of Schisandra extract. Full article

Cerebral ischemia results in increased oxidative stress in the affected brain. Accumulating evidence suggests that quercetin possesses anti-oxidant and anti-inflammatory properties. The essential elements magnesium (Mg), zinc (Zn), selenium (Se), and transition metal iron (Fe), copper (Cu), and antioxidants superoxide dismutase (SOD) and catalase (CAT) are required for brain functions. This study investigates whether the neuroprotective effects of quercetin on the ipsilateral brain cortex involve altered levels of essential trace metals, the Cu/Zn ratio, and antioxidant activity. Rats were intraperitoneally administered quercetin (20 mg/kg) once daily for 10 days before ischemic surgery. Cerebral ischemia was induced by ligation of the right middle cerebral artery and the right common carotid artery for 1 h. The ipsilateral brain cortex was homogenized and the supernatant was collected for biochemical analysis. Results show that rats pretreated with quercetin before ischemia significantly increased Mg, Zn, Se, SOD, and CAT levels, while the malondialdehyde, Fe, Cu, and the Cu/Zn ratio clearly decreased as compared to the untreated ligation subject. Taken together, our findings suggest that the mechanisms underlying the neuroprotective effects of quercetin during cerebral ischemic injury involve the modulation of essential elements, transition metals, Cu/Zn ratio, and antioxidant activity. Full article

The magnetic technique, consisting of a magnetic tracer and a handheld magnetometer, is a promising alternative technique for sentinel lymph node dissection (SLND) and was shown to be non-inferior to the standard technique in terms of identification rates. In this study, injection characteristics (iron dose, dilution, time course and massaging) were evaluated to optimize magnetic tracer uptake in the sentinel lymph nodes (SLN) in a rat hindleg model. 202 successful SLNDs were performed. Iron uptake in the SLN is proportional (10% utilization rate) to the injection dose between 20 and 200 μg, showing a plateau uptake of 80 μg in the SLN around 1000 μg injection. Linear regression showed that time had a higher impact than dilution, on the SLN iron uptake. Massaging showed no significant change in iron uptake. The amount of residual iron at the injection site was also proportional to the injection dose without any plateau. Time was a significant factor for wash-out of residual iron. From these results, preoperative injection may be advantageous for SLN detection as well as reduction in residual iron at the injection site by potential decrease in required injection dose. Full article

Current strategies for regeneration of large bone fractures yield limited clinical success mainly due to poor integration and healing. Multidisciplinary approaches in design and development of functional tissue engineered scaffolds are required to overcome these translational challenges. Here, a new generation of hyperelastic bone (HB) implants, loaded with superparamagnetic iron oxide nanoparticles (SPIONs), are 3D bioprinted and their regenerative effect on large non-healing bone fractures is studied. Scaffolds are bioprinted with the geometry that closely correspond to that of the bone defect, using an osteoconductive, highly elastic, surgically friendly bioink mainly composed of hydroxyapatite. Incorporation of SPIONs into HB bioink results in enhanced bacteriostatic properties of bone grafts while exhibiting no cytotoxicity. In vitro culture of mouse embryonic cells and human osteoblast-like cells remain viable and functional up to 14 days on printed HB scaffolds. Implantation of damage-specific bioprinted constructs into a rat model of femoral bone defect demonstrates significant regenerative effect over the 2-week time course. While no infection, immune rejection, or fibrotic encapsulation is observed, HB grafts show rapid integration with host tissue, ossification, and growth of new bone. These results suggest a great translational potential for 3D bioprinted HB scaffolds, laden with functional nanoparticles, for hard tissue engineering applications. Full article

Physiologically relevant iron-copper interactions have been frequently documented. For example, excess enteral iron inhibits copper absorption in laboratory rodents and humans. Whether this also occurs during pregnancy and lactation, when iron supplementation is frequently recommended, is, however, unknown. Here, the hypothesis that high dietary iron will perturb copper homeostasis in pregnant and lactating dams and their pups was tested. We utilized a rat model of iron-deficiency/iron supplementation during pregnancy and lactation to assess this possibility. Rat dams were fed low-iron diets early in pregnancy, and then switched to one of 5 diets with normal (1×) to high iron (20×) until pups were 14 days old. Subsequently, copper and iron homeostasis, and intestinal copper absorption (by oral, intragastric gavage with ⁶⁴Cu), were assessed. Copper depletion/deficiency occurred in the dams and pups as dietary iron increased, as evidenced by decrements in plasma ceruloplasmin (Cp) and superoxide dismutase 1 (SOD1) activity, depletion of hepatic copper, and liver iron loading. Intestinal copper transport and tissue ⁶⁴Cu accumulation were lower in dams consuming excess iron, and tissue ⁶⁴Cu was also low in suckling pups. In some cases, physiological disturbances were noted when dietary iron was only ~3-fold in excess, while for others, effects were observed when dietary iron was 10–20-fold in excess. Excess enteral iron thus antagonizes the absorption of dietary copper, causing copper depletion in dams and their suckling pups. Low milk copper is a likely explanation for copper depletion in the pups, but experimental proof of this awaits future experimentation. Full article

Hybrid clinical imaging is an emerging technology, which improves disease diagnosis by combining already existing technologies. With the combination of high-resolution morphological imaging, i.e., MRI/CT, and high-sensitive molecular detection offered by SPECT/PET/Optical, physicians can detect disease progression at an early stage and design patient-specific treatments. To fully exploit the possibilities of hybrid imaging a hybrid probe compatible with each imaging technology is required. Here, we present a hybrid nanoprobe for triple modality MR/SPECT/Fluorescence imaging. Our imaging agent is comprised of superparamagnetic iron oxide nanoparticles (SPIONs), labeled with ^99mTc and an Alexa fluorophore (AF), together forming ^99mTc-AF-SPIONs. The agent was stable in human serum, and, after subcutaneous injection in the hind paw of Wistar rats, showed to be highly specific by accumulating in the sentinel lymph node. All three modalities clearly visualized the imaging agent. Our results show that a single imaging agent can be used for hybrid imaging. The use of a single hybrid contrast agent permits simultaneous hybrid imaging and, more conventionally, allow for single modality imaging at different time points. For example, a hybrid contrast agent enables pre-operative planning, intra-operative guidance, and post-operative evaluation with the same contrast agent. Full article