A review of bioeffects of static magnetic field on rodent models

This review is aimed to summarize the experimental researches in the influences of static magnetic field on laboratory rodent models, reported by laboratory scientists, experimental technicians, clinical surgeons, animal veterinarians, and other researchers. Past studies suggested that static magnetic field-singly applied or used combined with other physical or chemical substances-significantly relieved some pains and ameliorated certain diseases in different organ systems, e.g. hypertension, osteoporosis, neuralgia, diabetes and leukemia etc. But on the other hand, some harmful events have also been observed in a number of investigations, from cellular level to fetal development. So exposure to static magnetic field might have dual effects on experimental rodent in various environments, viz. there are potentially therapeutic benefits, as well as adverse effects from it. The positive effect may relate to moderate intensities, while negative influence seems to be in connection with acute strong static magnetic fields. In addition, different orientations of static magnetic field exert different degrees of impact. Thus, the bioeffects of static magnetic field exposure on mice/rats depend on magnetic field intensities, durations and directions, though the exactly relationship between them is still vague. Further researches need to perform with appropriate methodologies, ingenious designs repeatedly and systemically, not only in animal models, but also in human volunteers and patients.     

Purple carrot extract protects against cadmium intoxication in multiple organs of rats: Genotoxicity,oxidative stress and tissue morphology analyses

The aim of this study was to investigate if purple carrot extract is able to protect against the noxious activities induced by cadmium exposure in multiple organs of rats. For this purpose, histopathological analysis, genotoxicity and oxidative status were investigated in this setting. A total of twenty Wistar rats weighing 250 g on the average, and 8 weeks age were distributed into four groups (n = 5), as follows: Control group (non-treated group, CTRL); Cadmium group (Cd) and Purple carrot extract groups at 400 mg/L or 800 mg/L. Histopathological analysis revealed that liver from animals treated with purple carrot extract improved tissue degeneration induced by cadmium intoxication. Genetic damage was reduced in blood and hepatocytes as depicted by comet and micronucleus assays in animals treated with purple carrot extract. SOD-CuZn and cytocrome C gene expression increased in groups treated with purple carrot extract. Purple carrot extract also reduced the 8OHdG levels in liver cells when compared to cadmium group. Taken together, our results demonstrate that purple carrot extract is able to protect against cadmium intoxication by means of reducing tissue regeneration, genotoxicity and oxidative stress in multiple organs of Wistar rats.     

Plasma membrane behavior,oxidative damage,and defense mechanism in Phanerochaete chrysosporium under cadmium stress

Microorganisms are essential for maintaining ecosystem balance, and understanding their response to toxic pollutants is important in assessing the potential environmental impacts of such releases. In this study, the response to the heavy metal cadmium and the potential defense or adaptive mechanisms of the widely used white-rot fungus, Phanerochaete chrysosporium, were investigated. The results indicated that cadmium causes plasma membrane damage, including rigidification of lipids, a decrease in H⁺-ATPase activity, and lipid peroxidation. The cellular death may be mediated by oxidative stress with mitochondria membrane potential (MMP) breakdown and reactive oxygen species (ROS) formation. Parts of the cells were able to survive by activating antioxidant defense systems (antioxidant agents and enzymes). Extracellular synthesis of cadmium crystal particles was observed after exposure to dissolved cadmium ion, which is probably another detoxification mechanism in which the dissolved metal is precipitated, thus reducing its bioavailability and toxicity. These physiological responses of P. chrysosporium to cadmium together with the defense mechanisms can provide useful information for the development of fungal-based technologies to reduce the toxic effects of cadmium.     

Brain most susceptible to cadmium induced oxidative stress in mice

Accumulated evidence over the years indicate that cadmium (Cd) may be a possible etiological factor for neurodegenerative diseases. This may possibly be linked to excessive generation of free radicals that damages the organs in the body depending on their defence mechanism. Since Cd is a toxic agent that affect several cell types, the aim of this study was to shed light on the effect of Cd and its consequences on different organs of the mice body. To test the hypothesis of concentration dependent Reactive Oxygen Species (ROS) generation and DNA damage, observations were done in the serum of 4–5 weeks old male Swiss albino mice by treating with cadmium chloride (CdCl₂) in drinking water for 30 days. The expression of Bcl-2-associated X protein (Bax) an apoptotic marker protein was two times higher in brain compared to liver at an exposure level of 0.5 mg L⁻¹ CdCl₂. Furthermore the correlation and linkage data analysis of antioxidant defence system revealed a rapid alteration in the brain, compared to any other organs considered in this study. We report that even at low dose of Cd, it impaired the brain due to lipid peroxidase sensitivity which favoured the Cd-induced oxidative injury in the brain.     

Effect of a static magnetic field on formaldehyde biodegradation in wastewater by activated sludge

The aim of this study was to determine the impact of a static magnetic field (MF) of 7 mT on formaldehyde (FA) biodegradation by activated sludge in synthetic wastewater. The MF had a positive effect on activated sludge biomass growth and dehydrogenase activity. The influence of the MF on the degradation process was observed with a FA concentration of 2400-2880 mg/l. Decreases in FA concentration and chemical oxygen demand (COD) were greater, by 30% and 26% respectively, than those in the control sample. At initial FA concentrations in raw wastewater of 2400 and 2880 mg/l, a decrease in the wastewater biodegradation efficiency was observed. This resulted in an increase of the ecotoxicity of the effluent to Daphnia magna. The value of the sludge biotic index (SBI) was dependent on the FA concentration in raw wastewater and the induction of the MF.     

Impact of a 1.5 T magnetic field on DNA damage in MRI-guided HDR brachytherapy

PurposeSome studies have suggested that the presence of a static magnetic field (SMF) during irradiation alters biological damage. Since MRI-guided radiotherapy is becoming increasingly common, we constructed a DNA-based detector to assess the effect of a 1.5 T SMF on DNA damage during high dose rate (HDR) brachytherapy irradiation.MethodsBlock phantoms containing a small cavity for the placement of plasmid DNA (pBR322) samples were 3-D printed with biocompatible tissue equivalent material. The phantom was CT scanned and an HDR brachytherapy treatment plan was designed to deliver 20 Gy and 30 Gy doses to the DNA samples in the presence and absence of a 1.5 T SMF. Relative yields of single- and double-strand breaks (SSBs and DSBs, respectively) were computed from gel electrophoresis images of the DNA band intensities and averaged over sample sizes ranging from 12 to 30. Radiation dose was also measured in the presence and absence of the 1.5 T SMF using GafChromic™ EBT3 film placed in the coronal, sagittal, and axial planes.ResultsThe average yield of DNA with SSBs and DSBs in the presence and absence of the SMF showed no statistically significant differences (all p ≥ 0.17). Differences in the net optical densities of the EBT3 films for each plane were within experimental uncertainty, suggesting no dose difference in the presence and absence of the SMF.ConclusionsHDR irradiation in the presence of the 1.5 T SMF did not alter dose deposition to the DNA cavity nor change SSB and DSB DNA damage.     

Apple juice attenuates genotoxicity and oxidative stress induced by cadmium exposure in multiple organs of rats

The aim of this study was to evaluate the health benefits associated with apple consumption following cadmium exposure. A total of 15 Wistar rats were distributed into three groups (n = 5), as follows: control group (non-treated group, CTRL); cadmium group (Cd) and apple juice group (Cd + AJ). The results showed a decrease in the frequency micronucleated cells in bone marrow and hepatocytes in the group exposed to cadmium and treated with apple juice. Apple juice was also able to reduce the 8OHdG levels and to decrease genetic damage in liver and peripheral blood cells. Catalase (CAT) was decreased following apple juice intake. Taken together, our results demonstrate that apple juice seems to be able to prevent genotoxicity and oxidative stress induced by cadmium exposure in multiple organs of Wistar rats.     

Role of antioxidants in protecting cellular DNA from damage by oxidative stress

We have previously derived 2 V79 clones resistant to menadione (Md1 cells) and cadmium (Cd1 cells), respectively. They both were shown to be cross-resistant to hydrogen peroxide. There was a modification in the antioxidant repertoire in these cells as compared to the parental cells. Md1 presented an increase in catalase and glutathione peroxidase activities whereas Cd1 cells exhibited an increase in metallothionein and glutathione contents. The susceptibility of the DNA of these cells to the damaging effect of H₂O₂ was tested using the DNA precipitation assay. Both Md1 and Cd1 DNAs were more resistant to the peroxide action. In the case of Md1 cells it seems clear that the extra resistance is provided by the increase in the two H₂O₂ scavenger enzymes, catalase and glutathione peroxidase. In the case of Cd1 cells the activities of these enzymes as well as of superoxide dismutases (Cu/Zn and Mn) are unaltered as compared to the parental cells. The facts that parental cells exposed to 100 μM Zn²⁺ in the medium exhibit an increase in metallothionein but not in glutathione and that these cells become more resistant to the DNA-damaging effect of H₂O₂ suggest that this protein might play a protective role in vivo against the OH radical attack on DNA.     

Increasing intracellular cAMP and cGMP inhibits cadmium-induced oxidative stress in rat submandibular saliva

The effect of cadmium on induction of oxidative stress in rat submandibular saliva and protective role of increasing intracellular cAMP and cGMP by use of specific phosphodiesterase inhibitors, theophylline and sildenafil were investigated. Pure submandibular saliva was collected intraorally by micro polyethylene cannula from anaesthetized rats using pilocarpine as secretagogue. Acute administration of cadmium (10 mg/kg) caused significant oxidative stress by increasing lipid peroxidation by-products (thiobarbituric reactive substances, TBARS) and decreasing total thiols and total antioxidant power of the saliva. Concurrent therapy of rats by theophylline (25 mg/kg) and sildenafil (5 mg/kg) prevented cadmium-induced oxidative stress in saliva. Theophylline and sildenafil inhibited cadmium-induced increase in lipid peroxidation and decrease in total thiols and antioxidant power. It is concluded that cadmium administration results in oxidative stress in rat submandibular saliva, which can be protected by concurrent administration of specific cyclic nucleotide phosphodiesterase inhibitors.     

The embryonic and post-embryonic development in two Drosophila species exposed to the static magnetic field of 60 mT

In this study, a static magnetic field influence on development and viability in two different species, Drosophila melanogaster and Drosophila hydei, was investigated. Both species completed development (egg–adult), in and out of the static magnetic field induced by double horseshoe magnet. Treated vials with eggs were placed in the gap between magnetic poles (47 mm) and exposed to the average magnetic induction of 60 mT, while control ones were kept far enough from magnetic field source. We found that exposure to the static magnetic field reduced development time in both species, but statistical significance was found only for D. hydei. Furthermore, we found that the average viability of both Drosophila species exposed to the magnetic field was significantly weaker compared to control ones. These results indicate that 60 mT static magnetic field could be considered as a potential stressor, influencing on different levels the embryonic and post-embryonic development of individuals.     

The Influence of a gradient static magnetic field on an unstirred Belousov-Zhabotinsky reaction

It is believed that static magnetic fields (SMF) cannot affect the pattern formation of the Belousov-Zhabotinsky (BZ) reaction, which has been frequently studied as a simplified experimental model of a nonequilibrium open system, because SMF produces no induced current and the magnetic force of SMF far below 1 T is too low to expect the effects on electrons in the BZ reaction. In the present study, we examined whether the velocity of chemical waves in the unstirred BZ reaction can be affected by a moderate-intensity SMF exposure depending on the spatial magnetic gradient. The SMF was generated by a parallel pair of attracting rectangular NdFeB magnets positioned opposite each other. The respective maximum values of magnetic flux density (B(max)), magnetic flux gradient (G(max)), and the magnetic force product of the magnetic flux density its gradient (a magnetic force parameter) were 206 mT, 37 mT/mm, and 3,000 mT(2)/mm. The ferroin-catalyzed BZ medium was exposed to the SMF for up to 16 min at 25 degrees C. The experiments demonstrated that the wave velocity was significantly accelerated primarily by the magnetic gradient. The propagation of the fastest wave front indicated a sigmoid increase along the peak magnetic gradient line, but not along the peak magnetic force product line. The underlying mechanisms of the SMF effects on the anomalous wave propagation could be attributed primarily to the increased concentration gradient of the paramagnetic iron ion complexes at the chemical wave fronts induced by the magnetic gradient.     

Cadmium toxicity in cultured tomato cells--role of ethylene, proteases and oxidative stress in cell death signaling

Our aim was to investigate the ability of cadmium to induce programmed cell death in tomato suspension cells and to determine the involvement of proteolysis, oxidative stress and ethylene. Tomato suspension cells were exposed to treatments with CdSO(4) and cell death was calculated after fluorescein diacetate staining of the living cells. Ethylene was measured in a flow-through system using a laser-driven photo acoustic detector; hydrogen peroxide was determined by chemiluminescence in a ferricyanide-catalysed oxidation of luminol. We have demonstrated that cadmium induces cell death in tomato suspension cells involving caspase-like proteases, indicating that programmed cell death took place. Using range of inhibitors, we found that cysteine and serine peptidases, oxidative stress, calcium and ethylene are players in the cadmium-induced cell death signaling. Cadmium-induced cell death in tomato suspension cells exhibits morphological and biochemical similarities to plant hypersensitive response and to cadmium effects in animal systems.     

Inhibition of pentylenetetrazole-induced seizure in mice by using a 4 Hz magnetic field: a comparative study with a 60 Hz magnetic field

We investigated the comparative effects of 4 and 60 Hz magnetic fields on pentylenetetrazole (PTZ)-induced seizure in mice. For this study, we measured the latent time to seizure, seizure duration, and lethality induced by PTZ in mice exposed to 4 and 60 Hz magnetic fields (MF) for 30 min. Compared to sham-exposed controls, the latent time to tail twitching and seizure in the 4 Hz MF group was significantly decreased while the latent time to seizure in the 60 Hz MF group was significantly increased. The seizure duration in the 4 Hz MF group was significantly decreased while that in the 60 Hz MF group was significantly increased. More importantly, while the mice exposed to a 60 Hz MF experienced significantly increased lethality after seizure convulsion, those exposed to a 4 Hz MF showed no lethality, with a shortening of the duration of seizure. This beneficial effect of a 4 Hz MF on seizure has the same implication as the anti-oxidative effects of a 4 Hz MF observed in our previous work. The results of our current and previous works indicate that a 4 Hz MF may be used as a therapeutic physical agent for the treatment of oxidative stress-induced diseases, including seizure, with or without chemical drugs.     

Impact of cadmium in T lymphocyte subsets and cytokine expression: differential regulation by oxidative stress and apoptosis

Cadmium (Cd), a possible human carcinogen is a potent immunotoxicant. In rodents it causes thymic atrophy and splenomegaly, in addition to immuno-suppression and modulation of humoral and/or cellular immune response. Oxidative stress and apoptosis appear to be underlying mechanism of Cd induced thymic injury. To understand the involvement of reactive oxygen species (ROS), intracellular glutathione (GSH) and apoptosis in modulation of T-cell repertoire, we studied the effect of Cd (10, 25 and 50 μM) on primary T lymphocytes of BALB/c mice at different time intervals (6, 12 and 18 h). We observed a dose and time dependent decline in CD4⁺/CD8⁺ ratio (a bio-indicator of immunotoxicity) as a result of significant suppression of CD4⁺ subsets (helper T-cells) and enhancement in CD8⁺ cells (cytotoxic T-cells) At the same time, the CD4⁺CD8⁺ (DP) cell population was lowered while the CD4⁻CD8⁻ (DN) cells were increased. The oxidative stress and apoptotic data revealed almost similar ROS generation in both CD4⁺ and CD8⁺ cells, but relatively more marked GSH depletion and apoptosis in CD4⁺ than in CD8⁺ population. On further analysis of CD4⁺ T-subsets, cytokine release (IL-2 and IFNγ) by Th 1 cells and IL-4 by Th 2 cells were shown to be significantly suppressed in a dose responsive manner. The highest inhibition was observed in IFNγ, then IL-2 followed by IL-4. In conclusion, our data demonstrates that T-cell apoptosis by Cd, more in CD4⁺ than in CD8⁺ cells appear related to higher depletion of intracellular glutathione. Th 1 cells of CD4⁺ sub-population are more responsive to Cd than Th 2, leading to higher suppression of IL-2 and IFNγ than IL-4 and hence, the study unravels to some extend, the underlying events involved in Cd immunotoxicity.     

Enhancement of natural killer cell cytotoxicity by using static magnetic field to increase their viability

Natural killer (NK) cells are innately immune to the body’s immune system and can actively recognize and kill cancer cells. This study explores the potential for enhancing the killing ability of NK cells by co-culturing the NK cells with the target cells under a static magnetic field (SMF). In this study, NK92-MI cell lines were cultured in the presence of a 0.4-T SMF. The effect of the SMF on NK cell viability was evaluated by means of an MTT assay. Culturing tests were performed with inhibitors of the DAG/IP3, STAT3, ERK, JNK and p38 pathways in order to examine the possible signaling cascade responsible for the SMF effect on the NK92-MI cell viability. Finally, the effect of the SMF on the cytotoxicity of the NK92-MI cells was evaluated by co-culturing the NK cells with K562 leukemia cell lines. The results showed that the application of a 0.4-T SMF significantly increased (p < 0.05) the viability of the NK92-MI cells. Furthermore, the inhibitor tests indicated that the SMF affected cell viability by activating multiple MAPK signaling pathways (ERKs, JNKs, and p38-MAPK). Finally, SMF pre-exposure for 48 hr significantly improved the killing activity of the NK92-MI cells (p < 0.05). That is, pre-exposure to SMF increased the viability of the NK92-MI cells and improved their killing ability against K562 tumor cells. In general, the present results suggest that NK cells pre-exposed to 0.4-T SMF show potential as a tool for immune-therapy treatment of cancer.     

Effect of prolonged exercise on oxidative damage and susceptibility to oxidants of rat tissues in severe hyperthyroidism

We investigated effects of prolonged aerobic exercise and severe hyperthyroidism on indices of oxidative damage, susceptibility to oxidants, and respiratory capacity of homogenates from rat liver, heart and skeletal muscle. Both treatments induced increases in hydroperoxide and protein-bound carbonyl levels. Moreover, the highest increases were found when hyperthyroid animals were subjected to exercise. These changes, which were associated to reduced exercise endurance capacity, were in part due to higher susceptibility to oxidants of hyperthyroid tissues. Levels of oxidative damage indices were scarcely related to changes in antioxidant enzyme activities and lipid-soluble antioxidant concentrations. However, the finding that, following exercise the scavenger levels generally decreased in liver homogenates and increased in heart and muscles ones, suggested a net shuttle of antioxidants from liver to other tissues under need. Aerobic capacity, evaluated by cytochrome oxidase activity, was not modified by exercise, which, conversely, affected the rates of oxygen consumption of hyperthyroid preparations. These results seem to confirm the higher susceptibility of hyperthyroid tissues to oxidative challenge, because the mechanisms underlying the opposite changes in respiration rates during State 4 and State 3 likely involve oxidative modifications of components of mitochondrial respiratory chain, different from cytochrome aa3.     

Investigation of inflammation,oxidative stress,and DNA damage in COVID-19 patients

COVID-19 disease, which spreads worldwide, is a disease characterized by widespread inflammation and affects many organs, especially the lungs. The resulting inflammation can lead to reactive oxygen radicals, leading to oxidative DNA damage. The pneumonia severity of 95 hospitalized patients with positive RT-PCR test was determined and divided into three groups: mild, moderate, and severe/critical. Inflammation markers (neutrophil–lymphocyte ratio, serum reactive protein, procalcitonin, etc.) were determined, and IL-10 and IFN-γ measurements were analyzed using the enzyme-linked immunosorbent assay method. In evaluating oxidative damage, total thiol, native thiol, disulfide, and ischemia-modified albumin (IMA) levels were determined by measuring spectrophotometrically. The comet assay method’s percentage of tail DNA obtained was used to determine oxidative DNA damage. As a result, when the mild and severe/critical groups were compared, we found that total thiol, native thiol, and disulfide levels decreased significantly in the severe/critical group due to the increase in inflammation markers and cytokine levels (p < 0.05). We could not detect any significance in IMA levels between the groups (p > 0.05). At the same time, we determined an increase in the tail DNA percent level, that is, DNA damage, due to the increased oxidative effect. As a result, we determined that inflammation and oxidative stress increased in patients with severe pneumonia, and there was DNA damage in these patients.     

Pharmacological consequences of oxidative stress in ocular tissues

The eye is a unique organ because of its constant exposure to radiation, atmospheric oxygen, environmental chemicals and physical abrasion. That oxidative stress mechanisms in ocular tissues have been hypothesized to play a role in diseases such as glaucoma, cataract, uveitis, retrolental fibroplasias, age-related macular degeneration and various forms of retinopathy provides an opportunity for new approaches to their prevention and treatment, In the anterior uvea, both H₂O₂ and synthetic peroxides exert pharmacological/toxicological actions tissues of the anterior uvea especially on the sympathetic nerves and smooth muscles of the iris–ciliary bodies of several mammalian species. Effects produced by peroxides require the presence of trace amounts of extracellular calcium and the functional integrity of mitochondrial calcium stores. Arachidonic acid metabolites appear to be involved in both the excitatory action of peroxides on sympathetic neurotransmission and their inhibitory effect on contractility of the iris smooth muscle to muscarinic receptor activation. In addition to the peroxides, isoprostanes (products of free radical catalyzed peroxidation of arachidonic acid independent of the cyclo-oxygenase enzyme) can also alter sympathetic neurotransmission in anterior uveal tissues. In the retina, both H₂O₂ and synthetic peroxides produced an inhibitory action on potassium depolarization induced release of [³H] d-aspartate, in vitro and on the endogenous glutamate and glycine concentrations in vivo. Effects caused by peroxides in the retina are mediated, at least in part, by second messengers such as nitric oxide, prostaglandins and isoprostanes. The ability of H₂O₂ to alter the integrity of neurotransmitter pools from sympathetic nerves in the anterior uvea and glutaminergic nerves in the retina could underlie its role in the etiology of glaucoma.     

Lead-induced oxidative damage in rats/mice: A meta-analysis

BackgroundLead (Pb) is ubiquitous in the environment and is an environmental genotoxic metal. Pb accumulation in the body could cause the oxidative stress.ObjectiveThis meta-analysis aimed to perform a systematic evaluation of the extent of oxidative damage in rats/mice induced by lead.MethodsAll relevant articles in English or Chinese were retrieved from Embase, PubMed, Web of Science, Medline, China National Knowledge Infrastructure, and Chinese Biological Medicine databases from their inception date until July 22, 2018.ResultsA total of 108 eligible articles were included in this study. The indicators of oxidative stress included malondialdehyde (MDA), glutathione disulfide (GSSG), reactive oxygen species (ROS), hydrogen peroxide (H₂O₂), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), reduced glutathione (GSH), superoxide dismutase (SOD), and glutathione-s-transferase (GST). The meta-analysis showed that lead significantly increased oxidants levels, such as MDA, GSSG, ROS, and H₂O₂ (P < 0.05), and significantly reduced the level of antioxidants, such as CAT, GPx, GR, GSH, SOD, and GST (P < 0.05). The intraperitoneal mode was more effective than water drinking mode in reducing the levels of CAT, GPx, GSH, and SOD (P < 0.05). Other factors that influenced the overall oxidative stress, including species of animals, type of tissues, and intervention dosage and time, were comprehensively evaluated.ConclusionThe results of meta-analysis indicated that mice were more sensitive to lead than rats, and intraperitoneal mode was an effective intervention mean. High doses and long periods of lead treatment can cause serious oxidative damage. Moreover, testicular was more vulnerable to lead than other tissues. These results provided scientific evidence for preventing and treating lead toxicity.