Exploration of the establishment of manganese poisoning rat model and analysis of discriminant methods

Tian, Yutian; Chen, Cengceng; Guo, Shuhan; Zhao, Li; Yan, Yongjian

doi:10.1016/j.tox.2018.08.006

Cited by 17 publications

(5 citation statements)

References 19 publications

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“…All protocols for this study were endorsed by the Guizhou Medical University Laboratory Animal Care and Use Committee under the approved (programme number: 1900218). 25,26 These data suggested that these doses can induce neurotoxic effects in rats. The experiments were conducted for a total of 16 weeks, 5 days a week and once a day.…”

Section: Animalsmentioning

confidence: 90%

“…Rats that had been acclimated for a week were sorted into four groups at random ( n = 15 each group): (i) control group (intraperitoneal injection of sterile pure water); (ii) low Mn group (intraperitoneal injection of 5 mg/kg dose of MnCl 2 ⋅4H 2 O solution); (iii) medium Mn group (intraperitoneal injection of 10 mg/kg MnCl 2 ⋅4H 2 O solution); (iv) high Mn group (intraperitoneal injection of 15 mg/kg MnCl 2 ⋅4H 2 O solution). The dose of MnCl 2 ⋅4H 2 O was determined according to our previous work and related studies 25,26 . These data suggested that these doses can induce neurotoxic effects in rats.…”

Section: Methodsmentioning

confidence: 99%

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Manganese induces oxidative damage in the hippocampus by regulating the expression of oxidative stress‐related genes via modulation of H3K18 acetylation

Chen,

Ao,

Liu

et al. 2023

Environmental Toxicology

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Prolonged exposure to manganese (Mn) contributes to hippocampal Mn accumulation, which leads to neurodegenerative diseases called manganese poisoning. However, the underlying molecular mechanisms remain unclear and there are no ideal biomarkers. Oxidative stress is the essential mechanisms of Mn‐related neurotoxicity. Furthermore, histone acetylation has been identified as being engaged in the onset and development of neurodegenerative diseases. Therefore, the work aims to understand the molecular mechanisms of oxidative damage in the hippocampus due to Mn exposure from the aspect of histone acetylation modification and to assess whether H3K18 acetylation (H3K18ac) modification level in peripheral blood reflect Mn‐induced oxidative damage in the hippocampus. Here, we randomly divided 60 male rats into four groups and injected them intraperitoneally with sterile pure water and MnCl2⋅4H2O (5, 10, and 15 mg/kg) for 16 weeks, 5 days a week, once a day. The data confirmed that Mn exposure down‐regulated superoxide dismutase activity and glutathione level as well as up‐regulated malondialdehyde level in the hippocampus and plasma, and that there was a positive correlation between these indicators in the hippocampus and plasma. Besides, we noted that Mn treatment upregulated H3K18ac modification levels in the hippocampus and peripheral blood and that H3K18ac modification levels correlated with oxidative stress. Further studies demonstrated that Mn treatment decreased the amounts of H3K18ac enrichment in the manganese superoxide dismutase (SOD2) and glutathione transferase omega 1 (GSTO1) gene promoter regions, contributing to oxidative damage in the hippocampus. In short, our results demonstrate that Mn induces oxidative damage in the hippocampus by inhibiting the expression of SOD2 and GSTO1 genes via modulation of H3K18ac. In assessing Mn‐induced hippocampal neurotoxicity, oxidative damage in plasma may reflect hippocampal oxidative damage in Mn‐exposed groups.

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Section: Animalsmentioning

confidence: 90%

Section: Methodsmentioning

confidence: 99%

Manganese induces oxidative damage in the hippocampus by regulating the expression of oxidative stress‐related genes via modulation of H3K18 acetylation

Chen,

Ao,

Liu

et al. 2023

Environmental Toxicology

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“…After continuous exposure to Mn, patients may experience decreased activity and extrapyramidal symptoms, followed by increased muscle tone, even after the cessation of exposure, these disorders are generally not alleviated as the damage is irreversible. 33 Continuous Fe exposure can also cause Parkinson's disease-like symptoms, including learning and memory dysfunction. 34 In animal studies, Mn and Fe have been shown to cause a series of neurological diseases, characterized by cognitive and behavioural disorders and attention deficits.…”

Section: Discussionmentioning

confidence: 99%

“…Due to their essentiality, both Fe and Mn readily accumulate in the CNS. After continuous exposure to Mn, patients may experience decreased activity and extrapyramidal symptoms, followed by increased muscle tone, even after the cessation of exposure, these disorders are generally not alleviated as the damage is irreversible 33 . Continuous Fe exposure can also cause Parkinson's disease‐like symptoms, including learning and memory dysfunction 34 .…”

Section: Discussionmentioning

confidence: 99%

Sodium para‐aminosalicylic acid attenuates combined manganese/iron‐induced cortical synaptic damage in rats

Song,

Xie,

Fang

et al. 2024

Basic Clin Pharma Tox

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We established experimental models of manganese (Mn) and iron (Fe) exposure in vitro and in vivo, and addressed the effects of manganese and iron combined exposure on the synaptic function of pheochromocytoma derived cell line 12 (PC12) cells and rat cortex, respectively. We investigated the protective effect of sodium para‐aminosalicylate (PAS‐Na) on manganese and iron combined neurotoxicity, providing a scientific basis for the prevention and treatment of ferromanganese combined neurotoxicity. Western blot and reverse transcription‐quantitative polymerase chain reaction (RT‐qPCR) were performed to detect the expression levels of protein and mRNA related to synaptic damage. Y‐maze novelty test and balance beam test were used to evaluate the motor and cognitive function of rats. Haematoxylin and eosin (H&E) and Nissl staining were performed to observe the cortical damage of rats. The results showed that the combined exposure of Mn and Fe in rats led to a synergistic effect, attenuating growth and development, and altering learning and memory as well as motor function. The combination of Mn and Fe also caused damage to the synaptic structure of PC12 cells, which is manifested as swelling of dendrites and axon terminals, and even lead to cell death. PAS‐Na displayed some antagonistic effects against the Mn‐ and Fe‐induced synaptic structural damage, growth, learning and memory impairment.

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“…For example, high dose of MnCl 2 injections (100 mg/kg, for 3–7 days) produced oxidative damage, mitochondria dysfunction, and neuroinflammation [ 28 ],moderate dose of MnCl 2 injections (6–15 mg/kg, 5/week for 4 weeks) altered brain dopamine levels and disrupted dopamine metabolism [ 30 ], and low dose of MnCl 2 (2.5 mg/kg) or MnO 2 (1.22 mg/kg) injections for 8–12 weeks altered brain neurotransmitters including decreased dopamine and its metabolites [ 29 ]. MnCl 2 (15–50 mg/kg) injections every 2 days for 12 weeks reduced tyrosine hydrolase (TH) expression in a dose-dependent manner [ 43 ]. Given the facts that Mn has a relatively shorter half-life in blood, yet fairly long half-lives in tissues [ 31 ] and chronic progressive feature of Manganism and PD, a longer recovery time between injections, and longer observation periods are desired to define chronic toxicity effects of Mn exposure.…”

Section: Introductionmentioning

confidence: 99%

Chronic Manganese Administration with Longer Intervals Between Injections Produced Neurotoxicity and Hepatotoxicity in Rats

et al. 2020

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Subacute exposure to manganese (Mn) produced Parkinson's disease-like syndrome called Manganism. Chronic onset and progression are characteristics of Manganism, therefore, this study aimed to examine Mn toxicity following chronic exposures. Male Sprague-Dawley rats were injected Mn 2+ 1 and 5 mg/kg, every 10 days for 150 days (15 injections). Animal body weight and behavioral activities were recorded. At the end of experiments, the brain and liver were collected for morphological and molecular analysis. Chronic Mn exposure did not affect animal body weight gain, but the high dose of Mn treatment caused 20% mortality after 140 days of administration. Motor activity deficits were observed in a dose-dependent manner at 148 days of Mn administration. Immunofluorescence double staining of substantia nigra pars compacta (SNpc) revealed the activation of microglia and loss of dopaminergic neurons. The chronic neuroinflammation mediators TNFα, inflammasome Nlrp3, Fc fragment of IgG receptor IIb, and formyl peptide receptor-1 were increased, implicating chronic Mn-induced neuroinflammation. Chronic Mn exposure also produced liver injury, as evidenced by hepatocyte degeneration with pink, condensed nuclei, indicative of apoptotic lesions. The inflammatory cytokines TNFα, IL-1β, and IL-6 were increased, alone with stress-related genes heme oxygenase-1, NAD(P)H:quinone oxidoreductase-1 and metallothionein. Hepatic transporters, such as multidrug resistant proteins (Abcc1, Abcc2, and Abcc3) and solute carrier family proteins (Slc30a1, Slc39a8 and Slc39a14) were increased in attempt to eliminate Mn from the liver. In summary, chronic Mn exposure produced neuroinflammation and dopaminergic neuron loss in the brain, but also produced inflammation to the liver, with upregulation of hepatic transporters.

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Exploration of the establishment of manganese poisoning rat model and analysis of discriminant methods

Cited by 17 publications

References 19 publications

Manganese induces oxidative damage in the hippocampus by regulating the expression of oxidative stress‐related genes via modulation of H3K18 acetylation

Manganese induces oxidative damage in the hippocampus by regulating the expression of oxidative stress‐related genes via modulation of H3K18 acetylation

Sodium para‐aminosalicylic acid attenuates combined manganese/iron‐induced cortical synaptic damage in rats

Chronic Manganese Administration with Longer Intervals Between Injections Produced Neurotoxicity and Hepatotoxicity in Rats

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