China ; Manganese/toxicity* ; Stainless Steel

Cognition Disorders ; chemically induced ; Humans ; Manganese ; toxicity ; Manganese Poisoning ; epidemiology

In this study, the general toxicity tests including acute toxicity test, haemolysis test, MTT assay of Ti-Fe-Mo-Mn-Nb-Zr alloys were carried out. The morphology of these cells was also observed under phase-contrast microscope. By using X-ray photoelectron spectroscopy(XPS), the kind and mol% of element in surface film were studied. The kind and concentration of element in dipping fluid were investigated by ICP atomic emission spectrometry. The results showed the primary component is TiO2 in surface film. The dipping fluid of Ti-Fe-Mo-Mn-Nb-Zr alloys contains Fe 0.2-1.07 mg/l and Mn 0.16-0.5 mg/l; such dental materials are beneficial to health. No cytotoxic effect was disclosed by in vitro and in vivo tests. The level of cytotoxicity was grade 0 and 1; the haemolysis degree was 0.558%-0.642%, i.e. less than 5%. The cells growing in the extract showed normal morphology. These data indicate that Ti-Fe-Mo-Mn-Nb-Zr alloy, as a dental material, has good biocompatibility.
Animals ; Biocompatible Materials ; chemistry ; toxicity ; Dental Alloys ; toxicity ; Iron ; toxicity ; Male ; Manganese ; Mice ; Molybdenum ; toxicity ; Niobium ; toxicity ; Osmotic Fragility ; Rabbits ; Random Allocation ; Spectrometry, X-Ray Emission ; Titanium ; toxicity ; Zirconium ; toxicity

OBJECTIVETo investigate the protective effect of the tert-butylhydroquinone (tBHQ) on PC12 cells from neurotoxicity induced by manganese.

METHODSCytotoxicity of PC12 cells was measured by MTT assay, following the PC12 cells treatment with different concentrations of MnCl₂ (300, 600, 900 μmol/L) for 24, 48 or 72 h. PC12 cells were pretreated with 40 μmol/L tBHQ for 12 h, followed by the treatment of 600 micromol/L or 300 μmol/L MnCl₂ for 72 h. Cytotoxicity of PC12 cells was measured by MTT assay, and cell apoptosis was examined by the method of Annexin V-FITC/PI in flow cytometry (FCM).

RESULTSThe proliferation of PC12 cells treated with 300, 600, 900 μmol/L MnCl2 was suppressed in the dose dependent pattern (P < 0.01). Proliferation of PC12 cells treated with 600 μmol/L MnCl₂ was suppressed to 40% of that in control group (P < 0.01), but the proliferation rate of PC12 cell pretreated with 40 μmol/L tBHQ was 180% of that in control group (P < 0.01). Apoptotic rate of PC12 cells treated with 300 micromol/L MnCl₂ was higher than the vehicle control group (P < 0.01). Apoptotic rate of 40 μmol/L tBHQ pretreatment followed by 300 μmol/L MnCl₂ treatment was lower than that of MnCl2 treatment group (P < 0.01). The inhibition rate of apoptosis was 61%.

CONCLUSIONSManganese may suppress PC12 cells proliferation and induce apoptosis. tBHQ can reduce PC12 cells proliferation suppressed by manganese and attenuate the apoptosis induced by manganese.

Animals ; Apoptosis ; drug effects ; Cell Proliferation ; drug effects ; Drug Antagonism ; Hydroquinones ; pharmacology ; Manganese ; toxicity ; PC12 Cells ; drug effects ; Rats

OBJECTIVE: To investigate the protective effects of curcumin(CUR) and its mechanism on a rat model of neurotoxicity induced by manganese chloride (MnCl₂), which mimics mangnism. METHODS: Sixty male SD rats were randomly divided into 5 groups, with 12 rats in each group. Control group received 0.9% saline solution intraperitoneally (ip) plus double distilled water (dd) H₂O intragastrically (ig), MnCl₂ group received 15 mg/kg MnCl₂(Mn²⁺ 6.48 mg/kg) intraperitoneally plus dd H₂O intragastrically, CUR group received 0.9% saline solution intraperitoneally plus 300 mg/kg CUR intragastrically, MnCl₂+ CUR1 group received 15 mg/kg MnCl₂ intraperitoneally plus 100 mg/kg curcumin intragastrically, MnCl₂+ CUR2 group received 15 mg/kg MnCl₂ intraperitoneally plus 300 mg/kg CUR intragastrically, 5 days/week, 4 weeks. Open-field and rotarod tests were used to detect animals' exploratory behavior, anxiety, depression, movement and balance ability. Morris water maze (MWM) experiment was used to detect animals' learning and memory ability. ICP-MS was used to investigate the Mn contents in striata. The rats per group were perfused in situ, their brains striata were removed by brains model and fixed for transmission electron microscope (TEM), histopathological and immunohistochemistry (ICH) analyses. The other 6 rats per group were sacrificed. Their brains striata were removed and protein expression levels of transcription factor EB (TFEB), mammalian target of rapamycin (mTOR), p-mTOR, Beclin, P62, microtubule-associated protein light chain-3 (LC3) were detected by Western blotting. Terminal deoxynucleotidyl transterase-mediated dUTP nick end labeling (TUNEL) staining was used to determine neurocyte apoptosis of rat striatum. RESULTS: After exposure to MnCl₂ for four weeks, MnCl₂-treated rats showed depressive-like behavior in open-field test, the impairments of movement coordination and balance in rotarod test and the diminishment of spatial learning and memory in MWM (P < 0.05). The striatal TH⁺ neurocyte significantly decreased, eosinophilic cells, aggregative α-Syn level and TUNEL-positive neurocyte significantly increased in the striatum of MnCl₂ group compared with control group (P < 0.05). Chromatin condensation, mitochondria tumefaction and autophagosomes were observed in rat striatal neurocytes of MnCl₂ group by TEM. TFEB nuclear translocation and autophagy occurred in the striatum of MnCl₂ group. Further, the depressive behavior, movement and balance ability, spatial learning and memory ability of MnCl₂+ CUR2 group were significantly improved compared with MnCl₂ group (P < 0.05). TH+ neurocyte significantly increased, the eosinophilic cells, aggregative α-Syn level significantly decreased in the striatum of MnCl₂+ CUR2 group compared with MnCl₂ group. Further, compared with MnCl₂ group, chromatin condensation, mitochondria tumefaction was alleviated and autophagosomes increased, TFEB-nuclear translocation, autophagy was enhanced and TUNEL-positive neurocyte reduced significantly in the striatum of MnCl₂+ CUR2 group (P < 0.05). CONCLUSION Curcumin alleviated the MnCl₂-induced neurotoxicity and α-Syn aggregation probably by promoting TFEB nuclear translocation and enhancing autophagy.
Animals ; Autophagy ; Chromatin ; Curcumin/pharmacology* ; Male ; Mammals ; Manganese/toxicity* ; Rats ; Rats, Sprague-Dawley ; Saline Solution/pharmacology* ; TOR Serine-Threonine Kinases

OBJECTIVETo observe the effects of manganese sulfate on blood pressure, myocardial ultrastructure and heart organ index of rats.

METHODSForty male SPF SD rats were randomly divided into 4 groups: control group (0 mg/kg), 5 mg/kg dose group, 15 mg/kg dose group and 25 mg/kg dose group, 10 rats each group. Intraperitoneal injection was performed for six months, by five times each week, the rat blood pressure was measured by tail cuff method, and the heart organ index of the rats was computed. Three rats were selected from each group randomly, and the myocardial ultrastructure of the rats was observed by using transmission electron microscopy (TEM). The BMD and BMDL between manganese sulfate injected dose and the rats heart organ index were evaluated by BMD (Benchmark Dose).

RESULTSThere was no significant of blood pressure between the experimental group and the control group (P > 0.05).The heart organ indexes of the four groups were 0.24% ± 0.10%, 0.25% ± 0.02%, 0.26% ± 0.02%, and 0.24% ± 0.02%. Statistical significance of heart organ indexes was found between the 15 mg/kg dose group and the control group (P < 0.05). Observed by TEM, we found that-different degrees of mitochondrial crest fracture or disappear, mitochondria swelling, hydropic change and myocardial fibers degeneration happened in the rats of the three exposed groups, but not the control group. The BMD and BMDL were calculated as 9.33 mg/kg and 4.28 mg/kg in the study of manganese sulfate injected dose and the rats heart organ index.

CONCLUSIONChronic manganese poisoning can lead to myocardial mitochondria superfine lesions, myocardial fiber damage and heart organ index change in rats.

Animals ; Male ; Manganese Compounds ; Mitochondria ; drug effects ; ultrastructure ; Myocardium ; ultrastructure ; Myocytes, Cardiac ; drug effects ; ultrastructure ; Rats ; Rats, Sprague-Dawley ; Sulfates ; toxicity ; Toxicity Tests

OBJECTIVES: Manganese chloride (MnCl2) is one of heavy metals for causing neurogenerative dysfunction like Manganism. The purpose of this study was to determine the acute toxicity of MnCl2 using different times and various concentrations including whether manganese toxicity may involve in two intrinsic pathways, endoplasmic reticulum (ER) stress and mitochondria dysfunction and lead to neuronal apoptosis mediated by organelle disorders in neuroblastoma cell line SK-N-MC. METHODS: In the acute toxicity test, five concentrations (200, 400, 600, 800, 1,000 uM) of MnCl2 with 3, 6, 12, 24, 48 hours exposure were selected to analyze cell viability. In addition, to better understand their toxicity, acute toxicity was examined with 1,000 uM MnCl2 for 24 hours exposure via reactive oxygen species (ROS), mitochondria membrane potential, western blotting and mitochondrial complex activities. RESULTS: Our results showed that both increments of dose and time prompt the increments in the number of dead cells. Cells treated by 1,000 microM MnCl2 activated 265% (+/-8.1) caspase-3 compared to control cell. MnCl2 induced intracellular ROS produced 168% (+/-2.3%) compared to that of the control cells and MnCl2 induced neurotoxicity significantly dissipated 48.9% of mitochondria membrane potential compared to the control cells. CONCLUSIONS: This study indicated that MnCl2 induced apoptosis via ER stress and mitochondria dysfunction. In addition, MnCl2 affected only complex I except complex II, III or IV activities.
Apoptosis ; Blotting, Western ; Caspase 3 ; Cell Line ; Cell Survival ; Chlorides ; Endoplasmic Reticulum ; Endoplasmic Reticulum Stress ; Manganese ; Manganese Compounds ; Membrane Potentials ; Metals, Heavy ; Mitochondria ; Neuroblastoma ; Neurons ; Organelles ; Reactive Oxygen Species ; Toxicity Tests, Acute

OBJECTIVETo study the anticlastogenic effect of redistilled cow's urine distillate (RCUD) in human peripheral lymphocytes (HLC) challenged with manganese dioxide and hexavalent chromium.

METHODSThe anticlastogenic activity of redistilled cow's urine distillate was studied in human polymorphonuclear leukocytes (HPNLs) and human peripheral lymphocytes in vitro challenged with manganese dioxide and hexavalent chromium as established genotoxicants and clastogens which could cause induction of DNA strand break, chromosomal aberration and micronucleus. Three different levels of RCUD: 1 microL/mL, 50 microL/mL and 100 microL/mL, were used in the study.

RESULTSManganese dioxide and hexavalent chromium caused statistically significant DNA strand break, chromosomal aberration and micronucleus formation, which could be protected by redistilled cow's urine distillate.

CONCLUSIONThe redistilled cow's urine distillate posseses strong antigenotoxic and anticlastogenic properties against HPNLs and HLC treated with Cr+6 and MnO2. This property is mainly due to the antioxidants present in RCUD.

Animals ; Antimutagenic Agents ; pharmacology ; Antioxidants ; pharmacology ; Cattle ; urine ; Cells, Cultured ; Chromium ; antagonists & inhibitors ; toxicity ; DNA Damage ; Humans ; Hydrogen-Ion Concentration ; Lymphocytes ; drug effects ; Manganese Compounds ; antagonists & inhibitors ; Mutagenicity Tests ; Mutagens ; toxicity ; Oxides ; antagonists & inhibitors ; toxicity ; Urine ; chemistry

OBJECTIVETo investigate the change of free Ca(2+) in cytoplasma in the neurotoxicity of the manganese (Mn).

METHODSThe cortical neurons were separated from the neonatal Wistar rats and cultured in vitro. The neurons were grouped as the Mn-treated groups and the untreated group. The neurons in the Mn-added groups were incubated in the culture media containing lower, medium and high dosage manganese chloride (MnCl(2 x 4) H2O) with the concentration at 0.2, 0.6, 1.0 mmol/L respectively. Meanwhile, neurons in control were cultured in the normal culture media. All treatments stopped 24 h later. Neurons were labeled Ca(2+) sensitive prober, Fluo-3/AM. The fluorescence intensity of Fluo-3 combined with Ca(2+) was examined by LSCM (Laser scanning confocal microscope) and was treated by the picture analysis technique. The intensity was equal to the free Ca(2+) concentrations in cytoplasma of neurons.

RESULTSMnCl(2) can induce free Ca(2+) overloaded in cytoplasma of neurons, but the increasing degree varied in MnCl(2) dosage. Cytoplasma Ca(2+) concentration in the moderate dosage The moderate dosage MnCl(2) group and the high dosage MnCl(2) group were significantly higher than that in the lower dosage MnCl(2) group and the control group (P < 0.05).

CONCLUSIONThe Ca(2+) overload is involved in the neurotoxicity of manganese, and a dosage response relationship is found between the manganese chloride dose and Ca(2+) overload in cortical neurons.

Animals ; Animals, Newborn ; Calcium ; metabolism ; Cells, Cultured ; Cerebral Cortex ; drug effects ; metabolism ; Dose-Response Relationship, Drug ; Manganese ; toxicity ; Neurons ; drug effects ; metabolism ; Rats ; Rats, Wistar

OBJECTIVETo investigate the relationship between genetic polymorphism of dopamine β-hydroxylase (DBH) and manganese-induced nerve injury.

METHODSIn a cross-sectional study, 402 electric welders who had worked over one year in relatively fixed sites were recruited, and the concentration of manganese in which they worked was stable. These samples was divided into high exposure group (CEI > 1) and low exposure group (CEI < 1) by CEI. Between the two groups, the groups were divided into abnormal group and normal group according to the result of neurologic check (there were 81 workers with abnormal neurological dysfunction in high exposure group and 28 workers in low exposure group, P < 0.05). Polymorphism of DBH gene was analyzed with polymerase chain reaction-restriction fragment length polymorphism.

RESULTSThe distribution of A2A2 genotype and A2 allele of DBH was significantly different. In high exposure group, the distribution of A2A2 genotype and A2 allele of DBH in abnormal group was significantly wider than in normal group (A2A2 genotype, OR = 1.248, P < 0.05, A2 allele, OR = 1.103, P < 0.05). In low exposure group, the distribution of A2 allele of DBH in abnormal group was significantly wider than in normal group (OR = 1.176, P < 0.05).

CONCLUSIONThe individuals who carry A2A2 genotype and A2 allele of DBH have increased risk of neurological dysfunction after explosion to manganese for a certain time, which suggests that polymorphism of DBH (intron 5 Taq I) would play a great role in hereditary susceptibility of neurological dysfunction cause by manganese.

Adult ; Air Pollutants, Occupational ; analysis ; toxicity ; Cross-Sectional Studies ; Dopamine beta-Hydroxylase ; genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Male ; Manganese ; analysis ; toxicity ; Middle Aged ; Nervous System Diseases ; genetics ; Polymorphism, Single Nucleotide ; Welding ; Young Adult