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Zongcan Zhou - One of the best experts on this subject based on the ideXlab platform.
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Manganese Chloride induced g0 g1 and s phase arrest in a549 cells
Toxicology, 2008Co-Authors: Peng Zhao, Weijian Zhong, Xianping Ying, Zhun Yuan, Zongcan ZhouAbstract:In the present study, we investigated the effects of Manganese Chloride (MnCl2) on cell cycle progression in A549 cells used as a model of Mn-induced lung toxicity. Cells were treated with various concentrations of MnCl2 (0, 0.01, 0.1, 0.5, 1.0 or 2.0 mM) for 24, 48 or 72 h. Cell proliferation was determined with MTT assay and mitotic index measurement and apoptosis was measured by flow cytometer. The results showed that MnCl2 inhibited A549 cells proliferation in a dose- and time-dependent manner, and induced apoptosis in A549 cells. When G0/G1 cells obtained by serum starvation were incubated with 0.5 mM of MnCl2 in the presence of 10% serum for several time intervals, the disruption of cell cycle progression was observed. The G0/G1 arrest was induced by MnCl2 treatment at 16 h and the arrest maintained for 8 h. Following the G0/G1 arrest, MnCl2 blocked the cells at S phase at 28 h and the S phase arrest maintained for at least 4 h. And moreover, proteasome inhibitor MG132 was able to prolong the duration of G0/G1 arrest induced by MnCl2 treatment. Results of western blotting assay revealed that cellular Cdk4, Cdk2 and phospho-Cdk2 (Thr160) levels decreased in Manganese-treated cells at both 20 and 28 h. In addition, the decreasing of Cyclin A level and the increasing of p53 and WAF1/p21 were also induced by MnCl2 treatment at 20 h. The expression of Cyclin D1, Cyclin E and Cdc25A proteins was not altered in Manganese-treated cells at both 20 and 28 h. Our results indicate that MnCl2 orderly induces G0/G1 and S phase arrest in A549 cells, the decreasing of Cdk4, Cdk2 and Cyclin A, and the increasing of p53 and Cdks inhibitor WAF1/p21 might be responsible for the G0/G1 arrest, and the decreasing of Cdk4 and Cdk2 levels for the S phase arrest.
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changes in the brain mitochondrial proteome of male sprague dawley rats treated with Manganese Chloride
Toxicology and Applied Pharmacology, 2005Co-Authors: Surong Zhang, Zongcan ZhouAbstract:To probe the mitochondrial involvement in Mn intoxicity, aliquots of brain mitochondria samples from control and treated (30 mg/kg Manganese Chloride, ip) male Sprague-Dawley rats were separated by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and searched for protein abundance changes induced by Mn exposure. The electrophoretic separation resolved over 300 distinct spots as visualized by colloidal Coomassie blue (CCB), of which three spots were induced and three spots were inhibited after Mn exposure in all the five brain mitochondria preparations. Analysis by matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) indicated that these spots are calcium-transporting ATPase type 2C (ATP-dependent Ca(2+) pump PMR1); 60-kDa heat shock protein; Mitochondrial transmembrane GTPase FZO1B; ATP-binding cassette, sub-family b; Long-chain-fatty-acid-CoA ligase; ATP Synthase Beta Chain; and Succinate dehydrogenase flavoprotein subunit. The changes of the mitochondrial ATP synthase beta-subunit and Succinate dehydrogenase flavoprotein subunit indicate an effected level of mitochondrial ATP content and/or ATP-producing capacity. This result provides suggestion that respiratory chain complexes were implicated in the mitochondrial dysfunction induced by Mn intoxicity. And the changes of 60-kDa heat shock protein and ATP-dependent Ca(2+) pump PMR1 expression indicate that the Ca homeostasis and stress effect were involved in Mn intoxicity.
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effect of Manganese Chloride exposure on liver and brain mitochondria function in rats
Environmental Research, 2003Co-Authors: Surong Zhang, Zongcan ZhouAbstract:Manganese (Mn) is an essential trace element found in many enzymes. As is the case for many essential trace elements, excessive Mn is toxic. Individuals suffering from Manganese toxicity exhibit several symptoms, which are similar to those frequently observed in cases of Parkinson's disease. In this investigation, we studied the effect of Manganese Chloride (7.5, 15.0, and 30.0 mg/kg body weight) on mitochondrial function and attempted to ascertain the mechanism of Manganese-induced mitochondrial dysfunction. The production of reactive oxygen species in mitochondria of rat liver and brain was assayed using 2',7'-dichlorofluorescin diacetate, and the activities of respiratory chain enzymes were examined spectrophotometrically. Monoamine oxidase (MAO) activity was assayed by measuring reduction of benzylamine. Manganese and calcium content in mitochondria were determined by atomic absorption spectrophotometry. These results indicate that Manganese Chloride (MnCl2) can decrease MAO activity and inhibit the respiratory chain. Manganese can accumulate in mitochondria and inhibit efflux of calcium. There is a significant inverse correlation between the amount of superoxide radicals and the specific activities of the mitochondria enzymes. Mitochondrial function was significantly affected in both males and females.
Zhixiong Shi - One of the best experts on this subject based on the ideXlab platform.
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Manganese effects in the liver following subacute or subchronic Manganese Chloride exposure in rats
Ecotoxicology and Environmental Safety, 2011Co-Authors: Peili Huang, Chunxia Chen, Hui Wang, Haiming Jing, Ying Han, Na Liu, Yang Xiao, Yuting Liu, Pengwen Wang, Zhixiong ShiAbstract:Manganese (Mn) toxicity is most often found in mining and welding industry workers. Accumulation of Manganese in the brain can result in a syndrome similar to that of Parkinson's disease. Observations on former Mn-alloy workers suggested that residual effects could last for years after exposure. The objective of this study was to assess effects of Mn in the liver of rats following subacute or subchronic exposure and after recovery. Male Sprague-Dawley rats were exposed to Manganese Chloride (MnCl(2)) for 30 days, 90 days, or for 90 days followed by a 30-day post-exposure recovery period. Results showed that MnCl(2) exposure resulted in liver injury in rats and the extent of injury correlated positively with exposure time. The effect in mitochondria was stronger than in the membrane or nucleus. Most of the changes in these biomarkers recovered when Manganese exposure ceased.
David C. Dorman - One of the best experts on this subject based on the ideXlab platform.
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olfactory toxicity in rats following Manganese Chloride nasal instillation a pilot study
Neurotoxicology, 2017Co-Authors: Melanie L Foster, Deepa B Rao, Taylor Francher, Samantha Traver, David C. DormanAbstract:Abstract Following inhalation, Manganese travels along the olfactory nerve from the olfactory epithelium (OE) to the olfactory bulb (OB). Occupational exposure to inhaled Manganese is associated with changes in olfactory function. This pilot study evaluated two related hypotheses: (a) intranasal Manganese administration increases OE and OB Manganese concentrations; and (b) intranasal Manganese exposure impairs performance of previously trained rats on a go-no-go olfactory discrimination (OD) task. Male Fischer 344 rats were trained to either lever press (“go”) in response to a positive conditioned stimulus (CS+: vanillin) or to do nothing (“no go”) when a negative conditioned stimulus (CS−: amyl acetate) was present. Following odor training, rats were randomly assigned to either a Manganese (200 mM MnCl2) or 0.9% saline treatment group (n = 4–5 rats/group). Administration of either saline or Manganese was performed on isoflurane-anesthetized rats as 40 μL bilateral intranasal instillations. Rats were retested 48 h later using the vanillin/amyl acetate OD task, then euthanized, followed by collection of the OE and OB. Manganese concentrations in tissue samples were analyzed by ICP-MS. An additional cohort of rats (n = 3–4/group) was instilled similarly with saline or Manganese and nasal and OB pathology assessed 48 h later. Manganese-exposed rats had increased Manganese levels in both the OE and OB and decreased performance in the OD task when compared with control animals. Histopathological evaluation of the caudal nasal cavity showed moderate, acute to subacute suppurative inflammation of the olfactory epithelium and submucosa of the ethmoid turbinates and mild suppurative exudate in the nasal sinuses in animals given Manganese. No histologic changes were evident in the OB. The nasal instillation and OD procedures developed in this study are useful methods to assess Manganese – induced olfactory deficits.
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nasal toxicity of Manganese sulfate and Manganese phosphate in young male rats following subchronic 13 week inhalation exposure
Inhalation Toxicology, 2004Co-Authors: David C. Dorman, Brian E. Mcmanus, Carl U Parkinson, Chris A Manuel, Anna M Mcelveen, Jeffrey I EverittAbstract:Growing evidence suggests that nasal deposition and transport along the olfactory nerve represents a route by which inhaled Manganese and certain other metals are delivered to the rodent brain. The toxicological significance of olfactory transport of Manganese remains poorly defined. In rats, repeated intranasal instillation of Manganese Chloride results in injury to the olfactory epithelium and neurotoxicity as evidenced by increased glial fibrillary acidic protein (GFAP) concentrations in olfactory bulb astrocytes. The purpose of the present study was to further characterize the nasal toxicity of Manganese sulfate (MnSO4) and Manganese phosphate (as hureaulite) in young adult male rats following subchronic (90-day) exposure to air, MnSO4 (0.01, 0.1, and 0.5 mg Mn/m3), or hureaulite (0.1 mg Mn/m3). Nasal pathology, brain GFAP levels, and brain Manganese concentrations were assessed immediately following the end of the 90-day exposure and 45 days thereafter. Elevated end-of-exposure olfactory bulb, striat...
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neurotoxicity of Manganese Chloride in neonatal and adult cd rats following subchronic 21 day high dose oral exposure
Journal of Applied Toxicology, 2000Co-Authors: David C. Dorman, Melanie F Struve, Domenico Vitarella, Faera L Byerly, Jennifer Goetz, Richard T MillerAbstract:The purpose of this study was to evaluate the relative sensitivity of neonatal and adult CD rats to Manganese-induced neurotoxicity. Identical oral Manganese Chloride (MnCl2) doses (0, 25, or 50 mg kg−1 body wt. day−1) were given to neonatal rats throughout lactation (i.e. from postnatal day (PND) 1 through 21) and to adult male rats for 21 consecutive days. The MnCl2 doses administered to neonates were ca. 100-fold higher than those resulting from the consumption of an equivalent volume of rat's milk. Rats were assessed using similar behavioral and neurochemical evaluations. Several statistically significant changes occurred in Mn-exposed rats relative to control animals. Neonates given the high dose of MnCl2 had reduced body weight gain. An increased pulse-elicited acoustic startle response amplitude was observed in neonates from both MnCl2 treatment groups on PND 21. Increased striatal, hippocampal, hindbrain and cortical Mn concentrations were observed in all Mn-exposed neonates on PND 21. Increased hypothalamic and cerebellar Mn concentrations were also observed on PND 21 in neonates from the high-dose group only. Increased striatal, cerebellar and brain residue Mn concentrations were observed in adult rats from the high-dose group. Increased striatal dopamine and 3,4-dihydroxyphenylacetic acid levels were observed only in PND 21 neonates from the high-dose group. No treatment-related changes were observed in clinical signs, motor activity (assessed in neonates on PND 13, 17, 21 ± 1 and in adults), passive avoidance (assessed in neonates on PND 20 ± 1 and in adults) or neuropathology (assessed in PND 21 neonates only). The results of our experiment suggest that neonates may be at greater risk for Mn-induced neurotoxicity when compared to adults receiving similar high oral levels of Mn. Copyright © 2000 John Wiley & Sons, Ltd.
Yasser S Elsayed - One of the best experts on this subject based on the ideXlab platform.
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neurohepatic toxicity of subacute Manganese Chloride exposure and potential chemoprotective effects of lycopene
Neurotoxicology, 2012Co-Authors: Mohamed A Lebda, Mahmoud S Elneweshy, Yasser S ElsayedAbstract:Abstract Excess Manganese (Mn) is potentially toxic resulting in a permanent neurodegenerative disorder, clinically known as “manganism” that is distinctive for hepaticencephalopathy. The present study was designed to explore the toxic impacts of subacute Mn exposure on brain and liver tissues, and the relative abilities of lycopene in averting such neurohepatic damage. Rats were daily injected with MnCl2 (0 or 6 mg/kg, i.p.) 20 days after lycopene administration (0 or 10 mg/kg, p.o.), and killed 4 weeks after MnCl2 exposure. MnCl2-induced lipid peroxidation and perturbation in antioxidant system, increase of acetylcholinesterase, aminotransferases, and decrease alkaline phosphatase, and lactate dehydrogenase activities with hyperglycemia as demonstrated by Alzheimer type II astrocytosis, and periportal hepatic necrosis and apoptosis were prevented by lycopene. However, lycopene did not prevent the increased body burden of Mn and the altered Fe and Cu homeostasis induced by MnCl2. Glutathione S-transferase and catalase activities, and glutathione content were reduced in MnCl2-challenged rats, and sustained by lycopene. Our results indicate that although lycopene failed to reduce Mn concentration or retain disturbed elemental status; it appears to be a highly effective in alleviating its neurohepatic deleterious effects by preventing lipid peroxidation, hyperglycemia and changes in the activity of acetylcholinesterase and hepatobiliary enzymes, and antioxidant pathways.
Peili Huang - One of the best experts on this subject based on the ideXlab platform.
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Manganese effects in the liver following subacute or subchronic Manganese Chloride exposure in rats
Ecotoxicology and Environmental Safety, 2011Co-Authors: Peili Huang, Chunxia Chen, Hui Wang, Haiming Jing, Ying Han, Na Liu, Yang Xiao, Yuting Liu, Pengwen Wang, Zhixiong ShiAbstract:Manganese (Mn) toxicity is most often found in mining and welding industry workers. Accumulation of Manganese in the brain can result in a syndrome similar to that of Parkinson's disease. Observations on former Mn-alloy workers suggested that residual effects could last for years after exposure. The objective of this study was to assess effects of Mn in the liver of rats following subacute or subchronic exposure and after recovery. Male Sprague-Dawley rats were exposed to Manganese Chloride (MnCl(2)) for 30 days, 90 days, or for 90 days followed by a 30-day post-exposure recovery period. Results showed that MnCl(2) exposure resulted in liver injury in rats and the extent of injury correlated positively with exposure time. The effect in mitochondria was stronger than in the membrane or nucleus. Most of the changes in these biomarkers recovered when Manganese exposure ceased.