Functional neurotoxicity of Mn-containing nanoparticles in rats

Oszlánczi, Gábor; Vezér, Tünde; Sárközi, Leila; Horváth, Endre; Kónya, Zoltán; Papp, András

doi:10.1016/j.ecoenv.2010.09.002

Cited by 57 publications

(28 citation statements)

References 29 publications

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“…In the ECoG of the SS cortex, size A and size B particles caused significant changes in the power spectrum of the ECoG, but size C particles (CL and CH groups) had no such effect. The-potentially responsible-local Mn level in the brain samples was not proportional to the applied dose but showed partial (AH vs. AL, CH vs. CL) or complete (BH vs. BL; Table 3) saturation, similar to our earlier study [45].…”

Section: Discussionsupporting

confidence: 81%

Size-Dependent Toxicity Differences of Intratracheally Instilled Manganese Oxide Nanoparticles: Conclusions of a Subacute Animal Experiment

Máté

Horváth

Kozma

et al. 2015

Biol Trace Elem Res

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Incomplete information on toxicological differences of micro- and nanometer-sized particles raised concerns about the effects of the latter on health and environment. Besides chemical composition, size and surface-to-volume ratio of nanoparticles (NPs) can affect toxicity. To investigate size-dependent toxicity differences, we used particles made of dioxide of the neurotoxic heavy metal manganese (Mn), typically found in inhaled metal fumes, in three size ranges (size A, 9.14 ± 1.98 nm; size B, 42.36 ± 8.06 nm; size C, 118.31 ± 25.37 nm). For modeling the most frequent route of exposure to Mn, NPs were given to rats for 6 weeks by intratracheal instillation. Of each NP size, 3 or 6 mg/kg body weight was given while control animals were vehicle treated. Neurotoxicity was assessed by measuring spontaneous locomotor activity in an open field and by recording spontaneous and evoked electrical activity from the somatosensory cortical area. Mn content of brain, lung, and blood, measured by ICP-MS, were correlated to the observed functional alterations to see the relationship between Mn load and toxic effects. Body weight gain and organ weights were measured as general toxicological indices. The toxicity of size A and size B NPs proved to be stronger compared to size C NPs, seen most clearly in decreased body weight gain and altered spontaneous cortical activity, which were also well correlated to the internal Mn dose. Our results showed strong effect of size on NP toxicity, thus, beyond inappropriateness of toxicity data of micrometer-sized particles in evaluation of NP exposure, differentiation within the nano range may be necessary.

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Section: Discussionsupporting

confidence: 81%

Size-Dependent Toxicity Differences of Intratracheally Instilled Manganese Oxide Nanoparticles: Conclusions of a Subacute Animal Experiment

Máté

Horváth

Kozma

et al. 2015

Biol Trace Elem Res

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“…*p \ 0.05, **p \ 0.01 denote statistical significance compared with control group; # p \ 0.05, ## p \ 0.01 denote statistical significance compared with 50 mg/kg MnCl 2 group. Magnification 9400 a previous study (Oszlánczi et al 2010), our findings demonstrated that Mn significantly reduced spontaneous activity. Excessive Mn accumulation in the striatum can result in a neurological syndrome, which can further lead to motor abnormalities (Cordova et al 2013).…”

Section: Discussionmentioning

confidence: 61%

Melatonin Antagonizes Mn-Induced Oxidative Injury Through the Activation of Keap1–Nrf2–ARE Signaling Pathway in the Striatum of Mice

Deng

Zhu

Mi³

et al. 2014

Neurotox Res

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Excessive manganese (Mn) exposure can lead to oxidative injury. Nuclear factor erythroid 2-related factor 2 (Nrf2) exerts an antioxidant response toward various environmental toxicants in the brain. However, the role of Nrf2 against Mn-induced oxidative injury remains largely unexplored. This study investigated the role of melatonin (MLT), an agent that was recently shown to induce the activation of the Kelch-like ECH-associated protein 1 (Keap1)-Nrf2-antioxidant response elements (ARE) pathway against manganism. Mice were randomly divided into six groups, including control, 12.5, 25, 50 mg/kg MnCl2, MLT control, and MLT + 50 mg/kg MnCl2. The following were determined: behavioral activity; pathological changes; immunofluorescence staining of Neuronal Nuclei and glial fibrillary acidic protein; cell apoptosis; the levels of reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH); the immunohistochemical expression; and the protein levels of Nrf2, Keap1, and downstream enzymes. Mn-induced motor disorders, pathological damage, neuron degeneration, astrocytes activation, apoptosis, ROS and MDA generation, and GSH depletion. Nrf2, keap1, heme oxygenase-1 and NAD(P)H dehydrogenase, and quinone 1 showed a biphasic expression trend, which was most evidenced in the 12.5 mg/kg MnCl2 group. Changes in γ-glutamylcysteine synthetase, glutathione peroxidase 1, glutathionine S-transferase, glutathione reductase, and superoxide dismutase decreased in a concentration-dependent manner as a result of Mn exposure. MLT antagonized oxidative injury through the activation of the Keap1-Nrf2-ARE signaling pathway. In conclusion, disturbance of the Keap1-Nrf2-ARE signaling pathway partly caused oxidative injury. MLT can activate Nrf2 and its downstream enzymes and reverse Mn-induced oxidative injury.

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“…In the spontaneous cortical activity (ECoG), the changes caused by Mn NP exposure were similar to those seen in earlier experiments (shift to higher frequencies: Oszlánczi et al, 2010) but were slight and below significance. Hence, any additional effect of the antioxidants could not be identified.…”

Section: Electrophysiological Effectssupporting

confidence: 65%

Functional neurotoxicity of arsenic and manganese as environmental agents and the possible protective role of natural antioxidants

Sárközi¹

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SUMMARYOxidative stress apparently plays a major role in the effect of several toxicants, including heavy metals, of environmental or occupational origin. It means inequilibrium between metabolic reactions producing reactive oxygen and nitrogen species (ROS and RNS), and the capacity of enzymatic and non-enzymatic reactions to neutralize these. In itself, oxidative stress is a side effect of oxidative energy production, which can be caused by exposure to a number of environmental xenobiotics, metals and others. Non-neutralized ROS and other radicals damage the nervous system, liver, kidneys etc. Free radicals are more and more held responsible for various chronic non-communicable diseases, and for aging. The central and peripheral nervous system is prone to oxidative damage, due to highly active mitochondrial energy production, to abundance of (unsaturated) structural lipids, and to low antioxidant defence capacity in the brain; and ROS may constitute the final common pathway for several neurotoxicants because oxidative damage to membrane lipids may lead to alterations of the membrane-bound functions crucial to the functioning of neurons. In the present thesis, the relationships of neurotoxicity, oxidative stress and antioxidant protection are investigated in case of two heavy metals with public health importance, arsenic (As) and manganese (Mn). Arsenic used to have numerous practical applications most of which have been discontinued because of the health risks. Its modern applications e.g. in semiconductors, are apparently safe. Increased presence of As in certain rocks may lead to human exposure by As emissions from mining and smelting non-ferrous metal ores or from burning coal with higher As content, but most importantly via drinking water. The problem of As in drinking water has been quite serious in several regions. According to WHO, As is among the ten most important chemicals of major public health concern. Arsenic occurs in various oxidation states in inorganic or organic compounds. Inorganic arsenite (As III ) is more toxic that arsenate (As V ), and most of the organic arsenicals are practically nontoxic. Arsenite strongly binds to the -SH group of proteins, inactivating various enzymes including those in the citrate cycle and terminal oxidation, depleting ATP pool and promoting the generation of ROS in the cells. It also increases oxidative stress by depleting reduced glutathione and thioredoxin. The consequences of chronic exposure to inorganic arsenic include nervous system damage. Electrophysiological data on As neurotoxicity are scarce, but in As-exposed workers altered EEG, visual evoked potentials, and peripheral nerve activity were detected, together with signs of oxidative stress. Manganese (Mn) can have the oxidation states -3 to 7+, indicating its propensity to redox reactions. Mn and its compounds have numerous technical applications (steelmaking, welding, nanotechnology etc). It is an essential trace element, required for normal brain function, and acting as cofactor for several enzyme...

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Functional neurotoxicity of Mn-containing nanoparticles in rats

Cited by 57 publications

References 29 publications

Size-Dependent Toxicity Differences of Intratracheally Instilled Manganese Oxide Nanoparticles: Conclusions of a Subacute Animal Experiment

Size-Dependent Toxicity Differences of Intratracheally Instilled Manganese Oxide Nanoparticles: Conclusions of a Subacute Animal Experiment

Melatonin Antagonizes Mn-Induced Oxidative Injury Through the Activation of Keap1–Nrf2–ARE Signaling Pathway in the Striatum of Mice

Functional neurotoxicity of arsenic and manganese as environmental agents and the possible protective role of natural antioxidants

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