It has been confirmed that exposure to various metal pollutants can induce neurotoxicity, which is closely associated with the occurrence and development of neurological disorders. Ferroptosis is a form of cell death in response to metal pollutant exposure and it is closely related to oxidative stress, iron metabolism and lipid peroxidation. Recent studies have revealed that ferroptosis plays a significant role in the neurotoxicity induced by metals such as lead, cadmium, manganese, nickel, and antimony. Lead exposure triggers ferroptosis through oxidative stress, iron metabolism disorder and inflammation. Cadmium can induce ferroptosis through iron metabolism, oxidative stress and ferroptosis related signaling pathways. Manganese can promote ferroptosis through mitochondrial dysfunction, iron metabolism disorder and oxidative stress. Nickel can promote ferroptosis by influencing mitochondrial function, disrupting iron homeostasis and facilitating lipid peroxidation in the central nervous system. Antimony exposure can induce glutathione depletion by activating iron autophagy, resulting in excessive intracellular iron deposition and ultimately causing ferroptosis. This article reviews the effects of metal pollutants on ferroptosis-related indicators and discusses the specific mechanisms by which each metal triggers ferroptosis. It provides a reference for identifying targets for preventing neurotoxicity and for developing treatment strategies for neurological disorders.
Ferroptosis/drug effects* ; Humans ; Iron/metabolism* ; Oxidative Stress/drug effects* ; Neurotoxicity Syndromes/metabolism* ; Cadmium/adverse effects* ; Animals ; Lipid Peroxidation/drug effects* ; Metals/metabolism* ; Lead/adverse effects* ; Environmental Pollutants/toxicity* ; Manganese/adverse effects* ; Nickel/adverse effects* ; Mitochondria/drug effects* ; Signal Transduction/drug effects*

OBJECTIVETo study the changes in the expression of divalent metal transporter 1 (DMT1) and ferroportin 1 (FP1) in the substantia nigra (SN) of rats with manganese-induced parkinsonism.

METHODSEighty Sprague-Dawley rats were randomly divided into four groups. Rats in the control group were injected intraperitoneally with saline solution. Rats in the low-dose, medium-dose, and high-dose groups were injected intraperitoneally with 5, 15, and 20 mg/kg MnC12 solution, respectively, for 16 weeks. Three behavioral tests were performed at the 16th week. The concentration of Mn2+ in the SN was determined by inductively coupled plasma-atomic emission spectrometry (ICP-AES), and the positive expression of tyrosine hydroxylase (TH) was measured by immunohistochemical staining to determine whether rats with manganese-induced parkinsonism were successfully produced. The expression of DMT1 and FP1 in SN was measured by immunohistochemical staining and fluorescent quantitative polymerase chain reaction.

RESULTSRats with manganese-induced parkinsonism were successfully produced using the above method. Compared with that in the control group, the concentrations of Mn2+ in the SN of rats exposed to 5, 15, and 20 mg/kg Mn2+ were significantly higher (1.72?0.33 vs 0.56 ± 0.20 µg/g, P<0.01; 2.92±0.77 vs 0.56±0.20 µg/g, P<0.01; 5.65±1.60 vs 0.56±0.20 µg/g, P<0.01). The mean ODs of TH-positive cells in the SN of rats exposed to 5, 15, and 20 mg/kg Mn+ were significantly lower than that in the control group (0.054±0.008 vs 0.109±0.019, P<0.01; 0.016±0.004 vs 0.109±0.019, P<0.01; 0.003±0.001 vs 0.109±0.019, P<0.01). Compared with that in the control group, the mean optical densities (ODs) of DMT1-positive cells in the SN of rats exposed to 15, and 20 mg/kg Mn2+ were significantly higher (0.062±0.004 vs 0.015±0.007, P<0.01; 0.116±0.064 vs 0.015±0.007, P<0.01). The mean ODs of FP1-positive cells in the SN of rats exposed to 5, 15, and 20 mg/kg Mn2+ were significantly lower than that in the control group (0.092±0.011 vs 0.306±0.081, P<0.01; 0.048±0.008 vs 0.306±0.081, P<0.01; 0.008±0.002 vs 0.306±0.081, P< 0.01). Rats exposed to 15 and 20 mg/kg Mn2+ had significantly higher expression of DMT1 mRNA in the SN than those in the control group (0.052±0.0126 vs 0.001±0.0004, P<0.05; 0.124±0.0299 vs 0.001±0.0004, P<0.05). However, rats exposed to 5, 15, and 20 mg/kg Mn2 had significantly lower expression of FP1 mRNA in the SN than those in the control group (0.059±0.0076 vs 0.162±0.0463, P<0.05; 0.033±0.0094 vs 0.162±0.0463, P< 0.05; 0.002±0.0007 vs 0.162±0.0463, P<0.05).

CONCLUSIONThe increased expression of DMT1 and reduced expression of FP1 may be involved in the processes of Mn2+ accumulation in the SN and dopaminergic neuron loss in rats with manganese-induced parkinsonism.

Animals ; Cation Transport Proteins ; metabolism ; Disease Models, Animal ; Manganese ; adverse effects ; Parkinsonian Disorders ; chemically induced ; metabolism ; RNA, Messenger ; Rats ; Rats, Sprague-Dawley ; Substantia Nigra ; metabolism ; physiopathology

OBJECTIVETo investigate the effect of long-term and low-level occupational Mn exposure on the level of uric acid (UA) in human urine.

METHODSIn this study, 65 volunteers were recruited, who were working on welding and foundry work in an plant in Gansu province, China. Additionally, 29 control samples were collected from individuals who did not have any history of excessive Mn exposure. An improved high performance liquid chromatography system equipped with a diode-array detector (HPLC-DAD) method was developed to determine the UA level in human urine. A Spectra AA 220 Atomic Absorption Spectrophotometer (AAS) was used to measure the Mn level in the urine.

RESULTSThe analytical method was validated for concentrations ranging from 3.82-45.84 μg/mL with acceptable accuracy, precision, and recovery. Overall, the UA levels of Mn exposure samples were significantly lower than that of control samples (P<0.05).

CONCLUSIONThe practical method developed here is suitable for both routine monitoring of UA level in human urine and metabolism research. Long-term and low-level occupational Mn exposure may lead to a lower UA level in urine, and UA might be an indicator of the early stage of manganism.

Adult ; Aged ; Chromatography, High Pressure Liquid ; Female ; Humans ; Male ; Manganese ; adverse effects ; Middle Aged ; Occupational Exposure ; adverse effects ; Sex Factors ; Uric Acid ; urine ; Young Adult

Adult ; Biomarkers ; blood ; urine ; Female ; Humans ; Male ; Manganese ; blood ; urine ; Middle Aged ; Occupational Exposure ; adverse effects ; Young Adult

OBJECTIVETo investigate the systemic changes of iron metabolism following manganese exposure.

METHODSNinety-seven welders and 91 workers with no history of exposure to manganese were recruited from the same factory in Beijing serving as the exposure group and the control group respectively. The welding rods used were type J422. The concentration of the manganese in the air of the work place was determined respectively with the national standard method. The serum iron and manganese, ferritin, transferrin and transferrin receptors were measured with the graphite furnace atomic absorption spectrophotometry and ELISA in both groups.

RESULTSThe permissible concentration-STEL of ambient Mn in welders' breathing zone ranged from 0.53 mg/m(3) to 2.19 mg/m(3), while the permissible concentration-TWA of ambient Mn was between 0.29 mg/m(3) and 0.92 mg/m(3) in the breathing zone of the workplace. Serum Mn and Fe concentrations in welders were about 1.40 times (P < 0.0l) and 1.2 times (P < 0.01), respectively, higher than those of control subjects. At the same time, the transferrin concentrations in serum were significantly higher (about 1.2 times, P < 0.05) in welders than in controls. In contrast, transferrin receptors were significantly lower (about 1.2 times) in exposed subjects than controls (P = 0.001). There was no difference in serum ferritin between the two groups (P = 0.112). Although there was no significant trend, the serum ferritin level was increased by 18% in comparison with that of the control. The abnormal percentage of serum Fe and Serum Mn in welders were 55.67% and 67.01% respectively, higher than those of control subjects. In addition, the correlations between all indicators and the duration of employment were not observed.

CONCLUSIONThe long term exposure to the manganese can induce the disorder of the iron metabolism, which is found in the expression of increase of the serum iron and transferrin as well as the decrease of transferrin receptors.

Female ; Ferritins ; blood ; Humans ; Iron ; metabolism ; Iron Metabolism Disorders ; chemically induced ; Male ; Manganese ; adverse effects ; Occupational Exposure ; adverse effects ; Receptors, Transferrin ; blood ; Transferrin ; analysis ; Welding