Doses Of Mn Research Articles

Metabolic Responses to Excess Manganese in Legumes: Variations in Nitrogen Compounds in Canavalia ensiformis (L.) DC and Cajanus cajan (L.) Millsp

ABSTRACTManganese (Mn) is crucial as a trace element for plant metabolism, but high concentrations in soil can induce symptoms of toxicity. This study aimed to evaluate the metabolism of nitrogen compounds and biomass production in Canavalia ensiformis and Cajanus cajan, clarifying the effects of this metal on nitrogen metabolism. The soil was treated with Mn concentrations of 80, 100, 120, 140, and 160 mg kg−1. Differential responses were observed in the metabolism of nitrogenous compounds between species. C. cajan affected nitrogen metabolism in shoots, roots, and nodules, with significant variations in amino acids, total soluble proteins, ureides, and root biomass concentration. In contrast, C. ensiformis showed stability in the concentrations of compounds, mainly ureides, and proteins, even with increasing doses of Mn in the soil. These findings highlight the importance of nitrogen metabolism in legumes studied as a key aspect for understanding their Mn tolerance mechanisms in soil.

Influence of subchronic exposure to manganese carried by female rats during pregnancy on the behavioral and cognitive abilities of their offspring at later stages of postnatal development

The study evaluated the effects of prenatal exposure to manganese (Mn) on the functional state of offspring at later stages of postnatal development (PND). Female rats were treated with MnSO4·5H2O in the diet at a dose of 1433 mg/kg starting 28 days prior to breeding and through gestation. The pregnancy proceeded normally, no physical abnormalities were observed. There was a lag in physical development of the offspring, which was characterized by a later opening of the eyes, the formation of a coat and the eruption of incisors, the weight gain was attenuated from PND 0-84. Offspring had hyperactive behavior and deterioration in spatial learning and memory. The level of Mn in the blood serum and cerebral cortex was higher than the control values by 11 % and 53 % respectively. The acetylcholinesterase level in the serum was higher by 47 %. These findings highlight the risk of prenatal exposure to subchronic doses of Mn.

Differential Mechanisms of Tolerance and Accumulation in Cajanus cajan (L.) Millsp. and Canavalia ensiformis (L.) DC in Response to Soil Manganese Concentration

ABSTRACT Cajanus cajan and Canavalia ensiformis are commonly used as cover crops due to their high biomass production, in addition they are also applied in recovery strategies for degraded areas. The objective of this study is to compare the tolerance, accumulation and translocation of Mn in the tissues of C. cajan and C. ensiformis, based on biomass production and the effects on the photosynthetic apparatus between species. The experiment was carried out in Red Latosol, contaminated with MnCl2 in the following concentrations: 0 (control), 80, 100, 120, 140 and 160 mg kg−1. Mn doses resulted in differentiated absorption, translocation and accumulation in plant organs, generating changes in the photosynthetic apparatus, reduction in dry mass and growth, and variations in tolerance and translocation levels between species. According to the results obtained, both species proved to be tolerant Mn and can be used in manganese management systems, they’re able to accumulate Mn in tissues, and not only maintain but also improve biomass production at intermediate doses, C. cajan indicates to be a better option for phytostabilization of Mn, on the other hand C. ensiformis, indicates to be a better option for phytoextraction of Mn in soils with contents up to 160 mg kg−1.

Synthesis, characterization and evaluation of novel manganese nanoclay polymer composite and nano‐MnO2 in wheat

AbstractBackgroundManganese (Mn) deficiency due to nutrient mining by high yielding cereal–cereal cropping patterns and forgetfulness of Mn fertilizer applications becomes potential challenge in crop production.AimNano‐enabled Mn fertilizers can be safer and more nutrient efficient than conventional Mn fertilizers (nutrient use efficiency ≈ 1%–3%). However, studies about nano‐Mn fertilizer synthesis and their behaviour in soil–plant system are rare.MethodsIn this study, two novel nano‐Mn fertilizers, that is nano‐MnO2 (NMO) and manganese nanoclay polymer composites (Mn‐NCPC), were synthesized, characterized (dynamic light scattering, X‐ray diffraction, Scanning electron microscopic and energy‐dispersive X‐ray, Fourier transform infrared spectroscopy etc.) and investigated for their impact on growth, yield and nutrient acquisition by wheat crop (Triticum aestivum L., variety HD‐2967) in a pot culture experiment. Treatment comprised 25%, 50% and 100% of recommended dose of Mn (RDMn) through NMO along with 100% RDMn through MnSO4·H2O (MS). Effect of exposure route was also investigated using foliar spray of NMO at tillering stage. Mn‐NCPC was found to be most efficient Mn fertilizer in terms of yield, Mn uptake and use efficiency by wheat crop.ResultsNano‐sized formulations improved the solubility of Mn in soil due to its higher active surface area (NMO) and slow‐release behaviour (Mn‐NCPC); thus, minimal losses happened due to the fixing of Mn in oxide/hydroxide forms. Application of 25% RDMn through NMO fertilizers maintained equitant diethylenetriamine pentaacetate Mn content to 100% RDMn through MnSO4·H2O. Mn‐NCPC stimulated the soil enzymatic activities, namely dehydrogenase, acid–alkaline phosphatase activities. Mn‐NCPC and NMO at 100% RDMn recorded 3.51% and 5.20% improvement in grain yield, respectively, when compared to MnSO4·H2O 100%.ConclusionsMn fertilizer doses can be reduced up to 25% of RDMn when applied through NMO or Mn‐NCPC fertilizers. However, effects of Mn‐NCPC and NMO need to be critically evaluated in long‐term field experiments in various cropping systems especially under cereal–cereal sequences for economic profitability and wide‐scale farmer's adaptability.

Divalent metal content in diet affects severity of manganese toxicity in Drosophila.

Dysregulation of manganese (Mn) homeostasis is a contributing factor in many neuro-degenerative diseases. Adult Drosophila are sensitive to excessive levels of dietary Mn, dying relatively early, and exhibiting biochemical and mobility changes reminiscent of Parkinsonian conditions. To further study Mn homeostasis in Drosophila, we sought to test lower levels of dietary Mn (5 mM) and noted a striking difference in Canton-S adult survivorship on different food. On a cornmeal diet, Mn-treated flies live only about half as long as untreated siblings. Yet, with the same Mn concentration in a molasses diet, adults survive about 80% as long as untreated siblings, and adults raised on a sucrose-yeast diet are completely insensitive to this low dose of dietary Mn. By manipulating metal ion content in the cornmeal diet, and measuring the metal content in each diet, we traced the difference in lifespan to the levels of calcium and magnesium in the food, suggesting that these ions are involved in Mn uptake and/or use. Based on these findings, it is recommended that the total dietary load of metal ions be considered when assessing Mn toxicity.

The damage caused by Cd toxicity to photosynthesis, cellular ultrastructure, antioxidant metabolism, and gene expression in young cacao plants are mitigated by high Mn doses in soil.

Manganese (Mn) is one of the essential mineral micronutrients most demanded by cacao. Cadmium (Cd) is highly toxic to plants and other living beings. There are indications that Mn can interact with Cd and mitigate its toxicity. The objective of this study was to evaluate the action of Mn on the toxic effect of Cd in young plants of the CCN 51 cacao genotype, subjected to different doses of Mn, Cd, and Mn+Cd in soil, through physiological, biochemical, molecular, and micromorphological and ultrastructural changes. High soil Mn doses favored the maintenance and performance of adequate photosynthetic processes in cacao. However, high doses of Cd and Mn+Cd in soil promoted damage to photosynthesis, alterations in oxidative metabolism, and the uptake, transport, and accumulation of Cd in roots and leaves. In addition, high Cd concentrations in roots and leaf tissues caused irreversible damage to the cell ultrastructure, compromising cell function and leading to programmed cell death. However, there was a mitigation of Cd toxicity when cacao was grown in soils with low Cd doses and in the presence of Mn. Thus, damage to the root and leaf tissues of cacao caused by Cd uptake from contaminated soils can be attenuated or mitigated by the presence of high Mn doses in soil.

Manganese overexposure induces Parkinson-like symptoms, altered lipid signature and oxidative stress in C57BL/6 J mouse

Although adequate intake of manganese (Mn) is essential to humans, Mn in excess is neurotoxic. Exposure to extremely high doses of Mn results in “manganism”, a condition that exhibits Parkinson-like symptoms. However, the mechanisms underlying its neurotoxic effects in Mn-induced parkinsonism pathogenesis are unclear. In this study, 8-week-old male C57BL/6 J mice were injected intraperitoneally with saline and 50 mg/kg MnCl2 respectively once daily for 14 days to produce an acute Mn neurotoxicity model. Accumulation of Mn in the midbrain, motor dysfunction and loss of dopaminergic neurons in the substantia nigra evidenced Mn neurotoxicity. Untargeted lipidomic analysis demonstrated that Mn overexposure altered lipidome profiles. A significant modulation of 12 lipid subclasses belonging to 5 different categories were found in the midbrain and among the most abundant lipids were sphingolipids, glycerophospholipids, and glycerides. The levels of sphingomyelin (SM) were significantly decreased after Mn treatment. The expression of SM biosynthesis genes was decreased dramatically while sphingomyelinase was up-regulated. In addition, we observed oxidative stress in both the midbrain of mice and MN9D cells, indicated by the increase of MDA level, the decrease of reduced GSH level and the inhibition of SOD and GPx enzyme activities. There was a correlation between these changes and motor dysfunctions. Overall, our study is the first to use lipidomics techniques to explore the pathogenesis of Mn-induced parkinsonism in C57BL/6 J mice. Mn induced molecular events in the midbrain, such as lipid metabolism disorders, oxidative stress and dopaminergic neurons injury, may mechanistically play important roles in the pathogenesis of Parkinson-like symptoms. Moreover, these findings emphasize the necessity for reducing the health risk of environmental neurotoxic pollutants in relation to parkinsonism.

Increasing soil Mn abundance promotes the dissolution and oxidation of Cr(III) and increases the accumulation of Cr in rice grains

Hexavalent chromium (Cr(VI)) is more readily taken up by plants than trivalent chromium (Cr(III)) due to its similar chemical structure to phosphate and sulfate. In paddy soils, Cr(VI) of natural origin are mainly produced from Cr(III) oxidized by O2 and Mn(III/IV) oxides, which are affected by rice radial oxygen loss (ROL) and Mn(II)-oxidizing microorganisms (MOM). However, little is known about the effect of ROL and Mn abundance on rice Cr uptake. Here, we investigated the effects on Cr(VI) generation and the subsequent Cr uptake and accumulation with the involvement of two rice cultivars with distinct ROL capacities by increasing soil Mn abundance. Results showed that Mn(II) addition to the soil led to more Cr(III) being released into the pore water, and the dissolved Cr(III) was oxidized to Cr(VI) by ROL and biogenic Mn(III/IV) oxides. The concentration of Cr(VI) in soil and pore water increased linearly with the addition of Mn(II) doses. Mn(II) addition promoted the root-to-shoot translocation and grain accumulation of Cr derived mainly from newly generated Cr(VI) in the soil. These results emphasize that rice ROL and MOM promote the oxidative dissolution of Cr(III) at a high level of soil Mn, resulting in more Cr accumulation in rice grains and increasing dietary Cr exposure risks.

TOLERANCE OF MARANDU GRASS TO EXCESS IRON AND MANGANESE

In soaked soils there is an increase in the availability of iron and manganese. Thus, it becomes important to investigate the tolerance levels of plants to excess of these nutrients. The objective was to evaluate the tolerance of Urochloa brizantha cv. Marandu cultivated in nutrient solution with different levels of iron and manganese. The experimental design was completely randomized with seven treatments and four replications. The treatments consisted of a nutrient solution and consisted of: 1- adequate concentration of Fe (8.22 mM) and Mn (2.05 mM); 2– Fe, four times the adequate concentration; 3– Fe, eight times the adequate concentration; 4– Mn, four times the adequate concentration; 5– Mn, eight times the adequate concentration; 6– Fe and Mn, four times the appropriate concentration, and; 7– Fe and Mn, eight times the appropriate concentration. The variables evaluated were visual diagnosis (symptomatology), shoot height, root volume, Fe and Mn content in shoots and dry mass production. Grass plants were not tolerant to excess Fe and Mn. The excess of nutrients promoted less development of the root system, with a reduction in volume and dry mass, and the treatment with the highest dose of nutrients resulted in the lowest values. Grass plants were sensitive to the increase in nutrient concentrations, showing reductions in total dry mass production of 55% for treatment with the application of the highest concentration of nutrients in relation to the adequate dose of Fe and Mn.

Effect of organic and inorganic manganese supplementation on performance and eggshell quality in aged laying hens.

Manganese (Mn) is an important trace element for laying hen's nutrition, which is required in small amounts in the diet. Its deficiency results in lowered production performance and eggshell quality. This experiment was conducted to investigate the influence of different sources and levels of Mn on egg production performance and eggshell quality in aged laying hens. A total of 720, 83-week-old Hy-Line W-36 laying hens were fed a non-Mn supplemented basal diet for 4-week (to ime Mn-exhaustion of body) and then were allocated to a completely randomized design with 10 treatments, six replicates and 12 birds each. Concentration of Mn in the non-Mn supplemented basal diet was 10.34 mg/kg (treatment 1), the added doses of dietary Mn were included 30, 60, and 90mg/kg of three different sources (Mn-oxide, Mn-sulphate, and Mn-organic) for treatments 2-10, respectively. The experiment lasted for 12 week. Dietary supplementation with either organic or inorganic Mn sources significantly enhanced egg production (EP), egg mass (EM), feed conversion ratio (FCR), and relative eggshell weight (RESW) compared with the non-Mn supplemented diet. However, the experimental diets did not influence feed intake (FI), egg weight, and other eggshell quality traits. Based on the broken line regression models, the performance traits were optimized at 30-40mg/kg Mn concentration when supplemented by Mn-sulphate or Mn-organic. Although, it was 80-90mg/kg when supplemented by Mn-oxide. The relative bio-efficacy of inorganic Mn sources include Mn-oxide and Mn-sulphate in compare with Mn-organic were estimated 45% and 87% (for EP trait), 30% and 94% (for EM trait), 36% and 99% (for FCR trait), and 37% and 78% (for RESW trait), respectively. In the aged laying hens, Mn requirement is higher than the NRC's recommendation. Sulphate and organic sources of Mn are more effective than Mn-oxide.

Acute manganese exposure impairs glutamatergic function in a young mouse model of Alzheimer’s disease

Manganese (Mn) is an essential metal that serves as a cofactor for metalloenzymes important in moderating oxidative stress and the glutamate/glutamine cycle. Mn is typically obtained through the diet, but toxic overexposure can occur through other environmental or occupational exposure routes such as inhalation. Mn is known to accumulate in the brain following exposure and may contribute to the etiology of neurodegenerative disorders such as Alzheimer’s disease (AD) even in the absence of acute neurotoxicity. In the present study, we used in vitro primary cell culture, ex vivo slice electrophysiology and in vivo behavioral approaches to determine if Mn-induced changes in glutamatergic signaling may be altered by genetic risk factors for AD neuropathology. Primary cortical astrocytes incubated with Mn exhibited early rapid clearance of glutamate compared to saline treated astrocytes but decreased clearance over longer time periods, with no effect of the AD genotype. Further, we found that in vivo exposure to a subcutaneous subacute, high dose of Mn as manganese chloride tetrahydrate (3 ×50 mg/kg MnCl2·4(H2O) over 7 days) resulted in increased expression of cortical GLAST protein regardless of genotype, with no changes in GLT-1. Hippocampal long-term potentiation was not altered in APP/PSEN1 mice at this age and neither was it disrupted following Mn exposure. Mn exposure did increase sensitivity to seizure onset following treatment with the excitatory agonist kainic acid, with differing responses between APP/PSEN1 and control mice. These results highlight the sensitivity of the glutamatergic system to Mn exposure. Experiments were performed in young adult APP/PSEN1 mice, prior to cognitive decline or accumulation of hallmark amyloid plaque pathology and following subacute exposure to Mn. The data support a role of Mn in pathophysiology of AD in early stages of the disease and support the need to better understand neurological consequences of Mn exposure in vulnerable populations.

Manganese Pollution in Mining-Influenced Rivers and Lakes: Current State and Forecast under Climate Change in the Russian Arctic

Mining regions in different parts of the world have been associated with the significant pollution of water, sediments, and soils by manganese and other chemical elements. This study assessed the degree of geochemical transformation caused by open-pit extraction and processing of mineral resources in the Kovdorsky District of Murmansk Oblast, 20 km from the Russia–Finland border. A second objective was to predict further changes co-driven by industrial pressure and high climatic instability in the polar region. The field study involved sampling water and sediments from virgin background streams and from the tailings storage facility, settling ponds, rivers, and lakes affected by ore mining and disintegration. Laboratory analyses included the study of elemental composition, redox potential, alkalinity and acidity, organic matter content, and other geochemical characteristics for a better understanding of pollutant migration patterns. We revealed elevated levels of potentially toxic elements in surface waters and bottom sediments which pose a risk to the human health via the household and drinking water supply. Pollution with manganese (Mn) was found to be the major environmental issue. Its natural presence in the river water was overridden a hundredfold by anthropogenic enrichment. This is problematic as Mn is easily bioaccumulated, which can lead to unwanted ecotoxicological effects, and—in the case of prolonged exposure to high doses of Mn and its compounds—to detrimental human health impacts. We believe that the changing climate may raise the water flow and thus expand the area of the hydrochemical anomaly. On the other hand, the activation of self-purification and dilution processes could lead to decreasing environmental Mn concentrations.

135 Vitamin E and Selenium Effects on White-tailed Deer Conception Success in Artificial Insemination Programs

Abstract The white-tailed deer breeding industry has developed into a $1.6 billion-dollar annual sector. However, even with this rapidly growing industry, little is known concerning certain mineral requirements for deer raised in confinement and their conception success. Previous research has suggested that white-tailed does are more apt to conceive with elevated circulating levels of zinc, vitamin E, and selenium. This research project consisted of ninety-three does on standard confinement diets, supplemented with only a single dose of Zn, Se, Mn, and Cu via MultiMin at the time of CIDR input. Supplementation of MultiMin was fixed across all animals in the study. These does were assessed by drawing blood at the time of artificial insemination (AI). Whole blood and serum samples were analyzed for micromineral levels (Co, Cu, Fe, Mn, Mo, Se, and Zn) and fat-soluble metabolites (vitamin A, vitamin E, and cholesterol) at Texas Veterinary Diagnostic Laboratory and analyzed using PROC REG in SAS. Conception success was determined by the does conceiving a fawn from from artificial insemination procedure which was verified via genetic testing of the fawn. It was found that the model containing the main effects vitamin E, zinc, and selenium along with their interactions of vitamin E by Zn and Se by Zinc was significant (P < 0.05; R2=0.15) on positively affecting conception success from artificial insemination. In particular, a tendency was detected in the relationship of vitamin E and selenium (P < 0.1). In post hoc analysis, parameter estimates from the regression were used, and selenium fixed at a level of 144 ng/mL is the point at which supplemental vitamin E has positive effects on conception from AI. This model shows that both vitamin E and selenium are required at higher levels than previously thought in confinement-reared white-tailed deer with intensive breeding programs. With further research using vitamin E and selenium, the mineral requirements of white-tailed deer in confinement can be better understood and aide producers in reproductive efficiency in their captive deer herds.

Heat shock proteins took part in oxidative stress-mediated inflammatory injury via NF-κB pathway in excess manganese-treated chicken livers

Manganese (Mn) is an essential metal in humans and animals. However, excess Mn entered environment due to the wide application of Mn in industry and agriculture, and became an environmental pollutant. Exposure to high doses of Mn is toxic to humans and animals (including chickens). Liver is a target organ of Mn poisoning. Nevertheless, there were few studies on whether Mn poisoning damages chicken livers and poisoning mechanism of Mn in chicken livers. Herein, the aim of this study was to explore if oxidative stress, heat shock proteins (HSPs), and inflammatory response were involved in the mechanism of Mn poisoning-caused damage in chicken livers. A chicken Mn poisoning model was established. One hundred and eighty chickens were randomly divided into one control group (containing 127.88 mg Mn kg−1) and three Mn-treated groups (containing 600, 900, and 1800 mg Mn kg−1, respectively). Histomorphological structure was observed via microstructure and ultrastructure. Spectrophotometry was used to detect total antioxidant capacity (T-AOC) and inducible nitric oxide synthase (iNOS) activity, as well as nitric oxide (NO) content. And qRT-PCR was performed to measure mRNA expression of inflammatory genes (nuclear factor kappa B (NF-κB), tumor necrosis factor α (TNF-α), cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and iNOS) and heat shock protein (HSP) genes (HSP27, HSP40, HSP60, HSP70, and HSP90). Multivariate correlation analysis, principal component analysis, and cluster analysis were used to demonstrate the reliability of mechanism of Mn poisoning in our experiment. The results indicated that excess Mn led to inflammatory injury at three contents and three time points. Meanwhile, we found that NO content, iNOS activity, and NF-κB, TNF-α, COX-2, PGE2, and iNOS mRNA expression increased after Mn treatment, meaning that exposure to Mn induced inflammatory response via NF-κB pathway in chicken livers. Moreover, excess Mn decreased T-AOC activity, indicating that Mn exposure caused oxidative stress. Furthermore, mRNA expression of above five HSP genes was up-regulated during Mn exposure. Oxidative stress triggered the increase of HSPs and the increase of HSPs mediated inflammatory response induced by Mn. In addition, there were time- and dose-dependent effects on Mn-caused chicken liver inflammatory injury. Taken together, HSPs participated in oxidative stress-mediated inflammatory damage caused by excess Mn in chicken livers via NF-κB pathway. For the first time, we found that oxidative stress can trigger HSP70 and HSPs can trigger poisoning-caused inflammatory damage, which needs to be further explored. This study provided a new insight into environmental pollutants and a reference for further study on molecular mechanisms of poisoning.

Gut Microbiota as a Potential Player in Mn-Induced Neurotoxicity.

Manganese (Mn) is an essential metal, which at high exposures causes neurotoxic effects and neurodegeneration. The neurotoxic effects of Mn are mediated by neuroinflammation, oxidative and endoplasmic reticulum stress, mitochondrial dysfunction, and other mechanisms. Recent findings have demonstrated the potential impact of Mn overexposure on gut microbiota dysbiosis, which is known to contribute to neurodegeneration via secretion of neuroactive and proinflammatory metabolites. Therefore, in this review, we discuss the existing data on the impact of Mn exposure on gut microbiota biodiversity, bacterial metabolite production, and gut wall permeability regulating systemic levels. Recent data have demonstrated that Mn exposure may affect gut microbiota biodiversity by altering the abundance of Shiegella, Ruminococcus, Dorea, Fusicatenibacter, Roseburia, Parabacteroides, Bacteroidetes, Firmicutes, Ruminococcaceae, Streptococcaceae, and other bacterial phyla. A Mn-induced increase in Bacteroidetes abundance and a reduced Firmicutes/Bacteroidetes ratio may increase lipopolysaccharide levels. Moreover, in addition to increased systemic lipopolysaccharide (LPS) levels, Mn is capable of potentiating LPS neurotoxicity. Due to the high metabolic activity of intestinal microflora, Mn-induced perturbations in gut microbiota result in a significant alteration in the gut metabolome that has the potential to at least partially mediate the biological effects of Mn overexposure. At the same time, a recent study demonstrated that healthy microbiome transplantation alleviates Mn-induced neurotoxicity, which is indicative of the significant role of gut microflora in the cascade of Mn-mediated neurotoxicity. High doses of Mn may cause enterocyte toxicity and affect gut wall integrity through disruption of tight junctions. The resulting increase in gut wall permeability further promotes increased translocation of LPS and neuroactive bacterial metabolites to the systemic blood flow, ultimately gaining access to the brain and leading to neuroinflammation and neurotransmitter imbalance. Therefore, the existing data lead us to hypothesize that gut microbiota should be considered as a potential target of Mn toxicity, although more detailed studies are required to characterize the interplay between Mn exposure and the gut, as well as its role in the pathogenesis of neurodegeneration and other diseases.

Chronic Manganese Exposure and the Enteric Nervous System: An in Vitro and Mouse in Vivo Study.

Background:Chronic environmental exposure to manganese (Mn) can cause debilitating damage to the central nervous system. However, its potential toxic effects on the enteric nervous system (ENS) have yet to be assessed.Objective:We examined the effect of Mn on the ENS using both cell and animal models.Method:Rat enteric glial cells (EGCs) and mouse primary enteric cultures were exposed to increasing concentrations of Mn and cell viability and mitochondrial health were assessed using various morphological and functional assays. C57BL/6 mice were exposed daily to a sublethal dose of Mn () for 30 d. Gut peristalsis, enteric inflammation, gut microbiome profile, and fecal metabolite composition were assessed at the end of exposure.Results:EGC mitochondria were highly susceptible to Mn neurotoxicity, as evidenced by lower mitochondrial mass, adenosine triphosphate–linked respiration, and aconitase activity as well as higher mitochondrial superoxide, upon Mn exposure. Minor differences were seen in the mouse model: specifically, longer intestinal transit times and higher levels of colonic inflammation.Conclusion:Based on our findings from this study, Mn preferentially induced mitochondrial dysfunction in a rat EGC line and in vivo resulted in inflammation in the ENS. https://doi.org/10.1289/EHP7877

English

Background: Manganese (Mn) being one of the micronutrients available in acid soils acts crucial role in crop plants. In Assam soil, its concentration is 3-52 ppm whereas in plants the critical limit is 2-3ppm. Although the effects Mn on plants have been well documented, information on its impacts on yield and yield components in upland rice crop grown in Assam was scanty, and deserved its investigation. Method: A pot experiment was carried out to study the effects of Mn (0, 10,20,30 ppm Mn as MnSO4H2O) foliar spray (each 1000cm3) at vegetative stage i.e.70days after sowing, on yield and yield components of ten rice genotypes (Kanaklata, Mulagabharu, Kapilee, Disang, Kolong, Joymoti, Jyoti Prasad, Luit, Lachit and Chilarai) cultivated in Assam. Conclusion: The lower dose of Mn (10ppm) significantly increased panicle length (16.29-37.46%), panicle weight (10.54-19.50%), panicle number per plant (4.54-13.63%), number of seeds per panicle (18.38-36.48%), test weight (7.21-29.15%), high density grains (5.59-30.45%), economic yield (14.40-28.03%), biological yield (32.58-47.70%), and harvest index (3.2-7.90%). 30ppm Mn affected adversely all the physiological attributes in the study. Among the ten genotypes, Kanaklata performed the best followed by Chilarai in the experiment.

Behavioral and neurochemical effects in mice after one-generation exposure to low doses of manganese: Focus on offspring development

The risk of exposure to toxic metals is a known concern to human populations. The overexposure to Mn can lead to a pathological condition, with symptoms similar to Parkinson's disease. Although toxicity of Mn has been reported, studies in neonates are scarce but necessary, as Mn can cross biological barriers. The present study evaluated if chronic perinatal exposure to Mn at low doses lead to neurotoxic effects in mice, after direct and indirect exposure. Couples of mice were exposed to Mn (0.013, 0.13, and 1.3 mg kg−1.day−1) for 60 days prior to mating, as well as during gestation and lactation. The offspring was distributed into two groups: animals that were not exposed after weaning - parental exposure only (PE); and animals subject to additional 60-day exposure through gavages after weaning - parental and direct exposure (PDE). Neurological effects were evaluated by Mn quantification, behavior tests and biochemical markers in the brain. PDE animals had alterations in short/long-term memory and increased anxiety-like behavior. Exposure to Mn triggered a decrease of glutathione-s-transferase and increase of cholinesterase activity in different regions of the brain. These findings highlight the risk of exposure to low doses of Mn over a generation and at early stages of development.

Effects of manganese on microglia M1/M2 polarization and SIRT1‐mediated transcription of STAT3‐dependent genes in mouse

Overexposure to manganese (Mn) can lead to neurological diseases, characterized by behavioral and motor impairments. Microglia-mediated neuroinflammation is involved in the pathogenesis and progression of neurodegenerative diseases. Microglial M1 and M2 phenotypes play pro-inflammatory and anti-inflammatory roles, respectively, in response to microenvironmental disturbances. Silent information regulator (SIRT1) has been demonstrated to play an important role in the neuroinflammatory response by deacetylating various transcription factors, such as proliferator-activated receptor γ coactivator 1α (PGC-1α), nuclear factor kappa B (NF-κB), and signal transducer and activator of transcription 3 (STAT3). In addition, PGC-1α and STAT3 have been implicated in microglial polarization and inflammatory response. In this study, Mn exposure (50, 100, 200μmol/kg) induced neuroinflammatory injury and interfered with microglial M1/M2 polarization in mice, as indicated by the upregulated expression of M1 polarization marker mRNA (IL-1β, IL-6, TNF-α, and iNOS), whereas changes in M2 polarization markers (IL-4, TGF-β, and Arg1) varied, with some increasing and some decreasing, in response to increasing Mn doses, which was consistent with the flow cytometry results used to detect the percentages of each microglial type. We found that Mn could downregulate SIRT1 expression and activate NF-κB signaling. Following mice in the 200 μmol/kg Mn treatment, STAT3 and PGC-1α levels in the nuclear fraction both significantly decreased, and the interaction between the proteins decreased, affecting the transcription of STAT3-mediated genes. These findings provide new insights regarding the role played by Mn neurotoxicity in the suppression of neuroinflammation through the regulation of microglial polarization.

Hepatic oxidative damage and Nrf2 pathway protein changes in rats following long-term manganese exposure.

This study investigated hepatic oxidative damage in rats following long-term manganese (Mn) exposure and clarified the underlying mechanisms. Forty-eight rats (SPF, male) were randomly assigned to receive low (10 mg/kg, n = 16) or high doses of Mn (50 mg/kg, n = 16) or sterilized distilled water (control group, n = 16). Rats were euthanized after 12 months, and liver Mn levels and histopathological changes were determined. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and liver malondialdehyde (MDA), glutathione peroxidase (GSH-PX), nuclear factor E2-related factor-2 (Nrf2), heme oxygenase-1 (HO-1), and NAD(P)H quinine oxidoreductase-1 (NQO1) levels were also determined. The Mn concentration and relative liver weights were significantly higher in the high-dose Mn group than in the control and low-dose Mn exposure groups. Low-dose Mn exposure resulted in mild expansion of hepatic sinuses and intact nuclei, whereas high-dose exposure led to pathological alterations in hepatocytes. High-dose Mn treatment significantly increased AST, ALT, and MDA activities and decreased GSH-PX activity. Additionally, liver Nrf2, HO-1, and NQO1 protein expression were markedly reduced by Mn exposure. Under the study conditions, long-term low-dose Mn exposure resulted in slight pathological changes in liver structure, but high-dose Mn exposure affected both liver structure and function, which might be related to the inhibition of Nrf2 expression, suppression of the transcription of its underlying antioxidant genes, and down regulation of the corresponding proteins. Consequently, the antioxidant capacity in the rat liver was weakened.