Increased whitening efficacy and reduced cytotoxicity are achieved by the chemical activation of a highly concentrated hydrogen peroxide bleaching gel

Abstract Objective This study was designed for the chemical activation of a 35% hydrogen peroxide (H2O2) bleaching gel to increase its whitening effectiveness and reduce its toxicity. Methodology First, the bleaching gel - associated or not with ferrous sulfate (FS), manganese chloride (MC), peroxidase (PR), or catalase (CT) - was applied (3x 15 min) to enamel/dentin discs adapted to artificial pulp chambers. Then, odontoblast-like MDPC-23 cells were exposed for 1 h to the extracts (culture medium + components released from the product), for the assessment of viability (MTT assay) and oxidative stress (H2DCFDA). Residual H2O2 and bleaching effectiveness (DE) were also evaluated. Data were analyzed with one-way ANOVA complemented with Tukey's test (n=8. p<0.05). Results All chemically activated groups minimized MDPC-23 oxidative stress generation; however, significantly higher cell viability was detected for MC, PR, and CT than for plain 35% H2O2 gel. Nevertheless, FS, MC, PR, and CT reduced the amount of residual H2O2 and increased bleaching effectiveness. Conclusion Chemical activation of 35% H2O2 gel with MC, PR, and CT minimized residual H2O2 and pulp cell toxicity; but PR duplicated the whitening potential of the bleaching gel after a single 45-minute session.

Autophagy Attenuates MnCl2-induced Apoptosis in Human Bronchial Epithelial Cells / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To investigate the role of autophagy in MnCl2-induced apoptosis in human bronchial epithelial 16HBE cells.</p><p><b>METHODS</b>Cell proliferation was measured by MTT assay. Mitochondrial membrane potential (MMP) and apoptosis were measured by flow cytometry. Autophagic vacuoles were detected by fluorescence microscopy. Cellular levels of apoptosis and autophagy-related proteins were measured by western blotting.</p><p><b>RESULTS</b>16HBE cell proliferation was inhibited by MnCl2 in a dose- and time-dependent manner. MnCl2-induced 16HBE cell growth inhibition was related to MMP depolarization prior to the induction of apoptosis. Our data revealed that MnCl2-induced apoptosis in 16HBE cells was mediated by decreased expression of Bcl-2 and increased levels of cleaved caspase-3. It was observed that when we exposed 16HBE cells to MnCl2 in a dose-dependent manner, the formation of autophagic vacuoles and the levels of LC-3B-II were elevated. RNA interference of LC3B in these MnCl2-exposed cells demonstrated that MMP loss and apoptosis were enhanced. Additionally, the pan-caspase inhibitor Z-VAD-FMK increased the cellular levels of Bcl-2 and decreased apoptosis, but did not affect the cellular levels of LC3B in MnCl2-treated 16HBE cells.</p><p><b>CONCLUSION</b>MnCl2 dose- and time-dependently inhibits 16HBE cell proliferation and induces MMP loss and apoptosis. Autophagy acts in a protective role against MnCl2-induced apoptosis in 16HBE cells.</p>

Effects of chronic manganese sulfate toxicity test on myocardial ultrastructure and heart organ index of rats / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To observe the effects of manganese sulfate on blood pressure, myocardial ultrastructure and heart organ index of rats.</p><p><b>METHODS</b>Forty 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).</p><p><b>RESULTS</b>There 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.</p><p><b>CONCLUSION</b>Chronic manganese poisoning can lead to myocardial mitochondria superfine lesions, myocardial fiber damage and heart organ index change in rats.</p>

Prevention of nonalcoholic steatohepatitis in rats by two manganese-salen complexes

Nonalcoholic steatohepatitis [NASH], a progressive stage of nonalcoholic fatty liver disease [NAFLD], is characterized by steatosis with inflammation. Investigations have suggested that oxidative stress may play an important role in the progress of NAFLD to NASH. To provide further insights into beneficial effects of antioxidants in NASH prevention, we employed two manganese-superoxide dismutase/catalase mimetics, manganese N,N-bis[salicyldene] ethylene diamine chloride [EUK-8] and manganese-3-methoxy N,N-bis[salicyldene] ethylenediamine chloride [EUK-134], as two salen representatives and vitamin C as the standard antioxidant Experimental NASH was induced in Male N-Mary rats by feeding a methionine/choline-deficient [MCD] diet to rats for 10 weeks. The rats [n = 5, 30 mg/kg/day] were randomly assigned to receive vitamin C, EUK-8, EUK-134 or vehicle orally Administration of salens together with the MCD diet reduced the serum aminotransferases, glutathione transferase and alkaline phosphatase, cholesterol, and LDL contents. In addition, the EUK-8 and EUK-134 improved NASH pathological features in liver of MCD-fed rats. EUK-8 and EUK-134 supplementation reduces NASH-induced abnormalities, pointing out that antioxidant strategy could be beneficial for prevention of NASH

MnCl2-induced functional damage of mitochondria in human lung cells in vitro / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the effect of MnCl(2) on the mitochondrial function of human lung cells, and to study the changes of protein expression level of nuclear respiratory factor-1 (NRF-1) in mitochondrial dysfunction induced by MnCl(2).</p><p><b>METHODS</b>The effects of MnCl(2) on cell survival rate were assessed by the reductions of tetrazolium dye (MTT) in cultured cell lines 16HBE and A549 cells. All tested16HBE and A549 cells were incubated with different concentrations of MnCl(2). The permeability transition pore (PTP) of mitochondria, mitochondrial membrane potential and the inhibition rate of mitochondrial enzymes as indicators of mitochondrial damage were measured by fluorescent spectrometry and MTT assay, respectively. Apoptosis was determined by flow cytometry. Protein levels of NRF-1 and mtTFA were measured by Western blot assay.</p><p><b>RESULTS</b>MnCl(2) decreased the survival rate of the two cell lines. The IC(50) of 16HBE and A549 cells were 1.91 mmol/L and 1.98 mmol/L, respectively. MnCl(2) caused a concentration-dependent decrease of mitochondrial enzymes and the inhibition rate of mitochondrial enzymes of the two cell lines induced by 1.00 mmol/L MnCl(2) were (52.8 ± 5.4)% and (50.6 ± 2.2)%, respectively. The PTP opening increased in MnCl(2)-treated cells in a dose- and time-dependent manner. Compared with the control group, mitochondrial membrane potential in the two cell lines was decreased by MnCl(2), by (7.9 ± 3.0)%, (26.2 ± 2.2)% and (27.8 ± 4.1)% in the 16HBE cells, and (4.7 ± 1.0)%, (14.9 ± 2.4)% and (27.5 ± 1.2)% in the A549 cells. Increased apoptosis rates of the two cell lines were induced by 1.00 mmol/L MnCl(2), (12.3 ± 1.9)% and (6.0 ± 0.4)%, respectively. The results of Western blot assay revealed that the protein levels of NRF-1 and mtTFA were decreased in manganese-treated cells in a dose-dependent manner, with a significant difference compared with that of the control cells (P < 0.05).</p><p><b>CONCLUSION</b>MnCl(2) induces mitochondrial dysfunction in 16HBE and A549 cells, and decreases the expression level of nuclear respiratory factor-1 (NRF-1), indicating that NRF-1 may play an important role in mitochondrial dysfunction.</p>

Apoptosis Induced by Manganese on Neuronal SK-N-MC Cell Line: Endoplasmic Reticulum (ER) Stress and Mitochondria Dysfunction

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.

Sensitive spectrophotometric assay of simvastatin in pharmaceuticals using permanganate / Ensaio espectrofotométrico sensíveis de sinvastatina em medicamentos utilizando permanganato

Two simple, sensitive, selective and inexpensive spectrophotometric methods are described for the determination of simvastatin (SMT) in bulk drug and in tablets using permanganate as the oxidimetric reagent. In method A, SMT is treated with a measured excess of permanganate in acetic acid medium and the unreacted oxidant is measured at 550 nm, whereas in method B the reaction is carried out in alkaline medium and the resulting manganate is measured at 610 nm. In method A, the amount of permanganate reacted corresponds to the SMT content and the absorbance is found to decrease linearly with the concentration; and in method B, the absorbance increases with concentration. The working conditions of assays were optimized, and the methods were validated according to the current ICH guidelines. Under optimum conditions, SMT could be assayed in the concentration ranges, 1.47 - 17.67x10-5 and 2.27 - 27.18 x10-6 mol/L by method A and method B, respectively. The calculated molar absorptivities are 3.2 x 10³ and 2.5 x 10(4) L/mol/cm for method A and method B, respectively with corresponding Sandell sensitivity values of 0.0387 and 0.0178 μg/cm². The limits of detection (LOD) and quantification (LOQ) have also been reported. Accuracy and precision for the assay were determined by calculating the intra-day and inter-day at three concentrations; the intra-day RSD was < 2 percent and the accuracy was better than 2.15 percent (RE). The methods were applied successfully for the determination of SMT in tablet dosage form with a high percentage of recovery, good accuracy and precision, and without measurable interference by the excipients. The accuracy was further ascertained from placebo and synthetic mixture analysis and also from the spike-recovery method.

Dois métodos espectrofotométricos simples, sensíveis, seletivos e baratos são descritos para a determinação de sinvastatina (SMT) a granel e em comprimidos, utilizando permanganato como reagente oxidimétrico. No método A, a SMT é tratada com excesso conhecido de permanganato em meio de ácido acético e o oxidante que não reage é medido a 550 nm, enquanto no método B, a reação é efetuada em meio alcalino e o manganato resultante é medido a 610 nm. No método A, a quantidade de permanganato que reage corresponde ao conteúdo de SMT e a absorbância diminui linearmente com o aumento da concentração; no método B, a absorbância aumenta com o aumento da concentração. As condições de trabalho do ensaio foram otimizadas e os métodos, validados de acordo com as normas do ICH. Sob condições ótimas, a SMT pode ser ensaiada nas faixas de concentração de 1,47- 17,67x10-5 e de 2,27-27,18 x10-6 mol/L pelo método A e B, respectivamente. As absortividades molares calculadas são 2 x 10³ e 2,5 x 10(4) L/ mol/cm, respectivamente, para os métodos A e B, com os valores correspondentes de sensibilidade de Sandell de 0,0387 e 0,0178 μg/cm². Os limites de detecção (LOQ) também foram relatados. A exatidão e a precisão do ensaio foram determinadas pelo cálculo de três concentrações intra- e inter-dia; a RSD intra-dia foi <2 por cento e a exatidão foi melhor que 2,15 por cento (RE). Os métodos foram aplicados com sucesso à determinação de SMT em comprimidos com alta porcentagem de recuperação, boa exatidão e precisão e sem interferência mensurável dos excipientes. A exatidão foi posteriormente determinada no placebo e na mistura sintética e, também, pelo método de spike recovery.

Comparative study on synthesis and characterizaton of ceria based composite oxides containing manganese nano-particles

Mn/Ce nano-composite oxides different amounts of manganese [5, 9, 17, 23, 29, 34 wt% as MnO[2]] were prepared by impregnation method at various calcinations temperatures. Effect of both thermal treatment and loading on the structural, surface and microstructure properties of the as prepared nano-composites was determined. The combined effect of manganese oxide and ceria, at different concentrations. Strongly influences the previous properties of the nano-composite oxides, by dispersing the MnO[2] phase and promoting the efficiency of the Ce[4+] - Ce[3+] and Mn[4+] - Mn[3+] redox couples. The thermal treatment and loading influences the interaction between manganese and CeO[2] evidently. The incorporation of Mn ions into CeO[2] cystal lattice resulted in weaker interaction between manganese and ceria on composite surface. Manganese loading at 400 [degree sign]C led to a slight increase in the ceria crystallite size which decreased by increasing the calcinations temperature from 400 to 600 [degree sign] C. The sintering activation energy of ceria was evaluated to be 12KJ/mol for the MnO[2]/Ce[O2] nano-composite

Ultrastructural changes of the olfactory bulb in manganese-treated mice

The effect of manganese toxicity on the ultrastructure of the olfactory bulb was evaluated. Male albino mice were injected intraperitoneally with MnCl2 (5 mg/Kg/day) five days per week during nine weeks. The control group received NaCl (0.9%). The olfactory bulbs of five mice from each group were processed for transmission electron microscopy after 2, 4, 6 and 9 weeks of manganese treatment. On week 2, some disorganization of the myelin sheaths was observed. After 4 weeks, degenerated neurons with dilated cisternae of rough endoplasmic reticulum and swollen mitochondria appeared. A certain degree of gliosis with a predominance of astrocytes with swollen mitochondria, disorganization of the endomembrane system, dilation of the perinuclear cisternae and irregularly shaped nuclei with abnormal chromatin distribution were observed after 6 weeks. Some glial cells showed disorganization of the Golgi apparatus. On week 9, an increase in the number of astrocytes, whose mitochondrial cristae were partially or totally erased, and a dilation of the rough endoplasmic reticulum were found. Neurons appear degenerated, with swollen mitochondria and a vacuolated, electron dense cytoplasm. These changes seem to indicate that the olfactory bulb is sensitive to the toxic effects of manganese.

Tinea Manus Caused by Trichophyton mentagrophytes var. erinacei Transferred from a Hedgehog / 대한피부과학회지

The hedgehog has recently become a fashionable pet in South Korea, especially among the younger persons. However, hedgehogs have been rarely reported to carry fungus that can cause human dermatomycosis. We report such a case. A 12-year-old boy was bitten by his hedgehog one week prior to presentation; he developed two clearly defined erythematous plaques with some pustules on the fingers. Periodic acid-Schiff stain of the biopsy specimen showed long, septated fungal hyphae in the keratin layer. KOH examination and fungus culture showed Trichophyton(T.) mentagrophytes. The subtype was identified as T. mentagrophytes var. erinacei by sequence analysis of the internal transcribed spacer regions of theribosomal DNA. The patient was treated with oral itraconazole (3.3 mg/kg, twice a day for 4 weeks) and topical ketoconazole cream with potassium permanganate wet dressings twice a day, resulting in complete resolution of the skin lesions.

Induction of Inducible Nitric Oxide Synthase Expression by Manganese in C6 Glioma Cells / 대한산업의학회지

OBJECTIVE: It is well established that manganese neurotoxicity is associated with clinical symptoms similar to those of idiopathic Parkinson's disease. Recent research has shown that the exposure to manganese (MnCl2) leads to induction of iNOS in BV2 microglial cells via iNOS transcriptional up-regulation and activation of both MAPKs and PI3K/Akt signaling pathways. Here, we further investigated the effect and the action mechanism of MnCl2 on iNOS expression in C6 glioma cells. METHODS: Western blot analyses demonstrated that treatment with MnCl2 at 250 micronmeter was sufficient to induce iNOS at both the protein and mRNA levels in C6 cells. RESULTS: These studies demonstrated that the induction of iNOS protein and mRNA was visible after 4h- and 2 h-treatment with MnCl2, respectively. MnCl2 treatment led to strong phosphorylation of JNKs and ERKs, members of MAP kinases (MAPKs), and Akt, a PI3-kinase (PI3K) downstream effector, in C6 cells. MnCl2 treatment had no effect on I kappa B-alpha in C6 cells. Notably, pretreatment with LY294002 (a PI3K inhibitor), which inhibited phosphorylation of Akt by MnCl2, caused strong suppression of MnCl2- induced iNOS protein and mRNA expression in C6 cells. Moreover, pretreatment with SP600125 (an inhibitor of JNKs) and PD98050 (an inhibitor of ERKs), which respectively interfered with MnCl2-mediated phosphorylation of JNKs and ERKs, led to the partial suppression of MnCl2-induced iNOS protein. Interestingly, pretreatment with LY294002 inhibited phosphorylation of not only Akt, but also ERKs and JNKs, in response to MnCl2. Moreover, there was an effective suppression of MnCl2-mediated phosphorylation of AKT by SP600125. CONCLUSION: These results collectively suggest that MnCl2 induces iNOS expression in C6 glioma cells via activation of PI3K/Akt and JNK-ERK MAPK signaling proteins, whose activations seem to be mutually interconnected in response to MnCl2.

The Production and Functions of Reactive Oxygen Species in Mouse Bone Marrow-derived Dendritic Cells by Various Haptens and Irritants / 대한피부과학회지

BACKGROUND: Various allergens and irritants induced the production of reactive oxygen species (ROS) in the well-established mouse dendritic cell (DC) line XS106 and this production of ROS was inhibited by antioxidants. OBJECTIVE: To investigate the production and functions of ROS in mouse bone marrow-derived DCs (BM-DCs) by various haptens and irritants, we examined the production of ROS, the expression of surface molecules, and the production of interleukin-12 (IL-12) in mouse BM-DCs. METHODS: Six to eight-week-old female C57/BL6 mice were used in this study. Mouse BM-DCs were co-cultured with DNFB, DNCB, TNBS, hydroquinone, NiSO4, CoCl2, MnCl2, thimerosal, SDS, and BKC. The production of ROS and the expression of surface molecules (CD40, CD80, CD86, and MHC-II) were measured by flow cytometry in chemical-treated mouse BM-DCs. In addition, the cells were pretreated with antioxidants to determine whether the production of ROS can be inhibited. The production of IL-12 was also measured in DNCB and SDS-treated mouse BM-DCs using ELISA. Results: The production of ROS in mouse BM-DCs was induced by various allergens, including DNFB, DNCB, TNBS, hydroquinone, MnCl2 and irritants like SDS, BKC. The expression of surface molecules was induced by various chemicals and NiSO4 was the most potent inducer of surface molecules in mouse BM-DCs. The production of ROS in DNCB and SDS-treated mouse BM-DCs was partially inhibited by diphenylene iodonium, but not by rotenone, vitamin E, allopurinol, glutathione. The production of IL-12 was not detected in DNCB and SDS-treated mouse BM-DCs. CONCLUSION: The production of ROS was induced in mouse BM-DCs by various allergens and irritants. The expression of surface molecules was also induced by various chemicals. The production of ROS was partially inhibited by DPI. The production of IL-12 was not detected.

Preparation and characterization of Mn-Zn ferrite oxygene nanoparticle for tumor thermotherapy / 生物医学工程学杂志

With the sulfate as the materials and NaOH as precipitator, Mn(0.4)Zn(0.6)Fe2O4 nanoparticles were produced, which are proved to be spinel Mn-Zn ferrite analyzed by X-ray diffraction(XRD). Their shapes are approximately global examined by transmission electron microscopy(TEM) and their average diameter is 50 nm measured with image analysis-system. The Curie temperature was measured and in vitro heating test in a alternating magnetic field was carried out. The results show that the Curie temperature is 105. 407 degrees C, While its magnetic fluid could rise to 43 degrees C - 47 degrees C due to different concentration in a alternating magnetic field. The result provide theoretical and practical evidence to select an appropriate material and concentration for tumor

Mechanism of reactive oxygen species in manganese chloride-induced apoptosis in PC12 cells / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To explore the mechanism of reactive oxygen species (ROS) in manganese chloride (MnCl(2))-induced apoptosis in PC12 cells.</p><p><b>METHODS</b>The model that MnCl(2) induced apoptosis in PC12 cells was established. The apoptotic effect of MnCl(2) on PC12 cells was analyzed with the MTT, the flow cytometry and the DNA fragmentation. The production of ROS and ATP in MnCl(2)-induced apoptosis of PC12 cells was examined. The influence of MnCl(2) on the expression of bcl-xl, bax and the activity of Caspase 3 was also analyzed.</p><p><b>RESULTS</b>MnCl(2) triggered PC12 cells apoptosis in a dose-and time-dependent manner (P < 0.01). The rate of apoptosis was significantly increased (P < 0.01) when MnCl(2) of 2 mmol/L induced PC12 cells for 36 hours. The production of ROS was increased (P < 0.001) and the quantity of ATP was decreased (P < 0.01) in PC12 cells with the same inducement of MnCl(2). The expression of bcl-xl was inhibited and the bax was activated in this process (P < 0.01). Caspase 3 was also activated (P < 0.01).</p><p><b>CONCLUSION</b>MnCl(2) induces apoptosis of PC12 cells, which is related to the increase of ROS, the inhibition of the mitochondria and the activation of Caspase 3.</p>

Anticlastogenic effect of redistilled cow's urine distillate in human peripheral lymphocytes challenged with manganese dioxide and hexavalent chromium / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To study the anticlastogenic effect of redistilled cow's urine distillate (RCUD) in human peripheral lymphocytes (HLC) challenged with manganese dioxide and hexavalent chromium.</p><p><b>METHODS</b>The 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.</p><p><b>RESULTS</b>Manganese 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.</p><p><b>CONCLUSION</b>The 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.</p>

Manganese antagonizes iron blocking mitochondrial aconitase expression in human prostate carcinoma cells / 亚洲男科学杂志(英文版)

<p><b>AIM</b>To investigate the possible role of manganese in the regulation of mitochondrial aconitase (mACON) activity human prostate carcinoma cell line PC-3 cells.</p><p><b>METHODS</b>The mACON enzymatic activities of human prostate carcinoma cell line PC-3 cells were determined using a reduced nicotinamide adenine dinucleotide-coupled assay. Immunoblot and transient gene expression assays were used to study gene expression of the mACON. The putative response element for gene expression was identified using reporter assays with site-directed mutagenesis and electrophoretic mobility-shift assays.</p><p><b>RESULTS</b>In vitro study revealed that manganese chloride (MnCl2) treatment for 16 h inhibited the enzymatic activity of mACON, which induced the inhibition of citrate utility and cell proliferation of PC-3 cells. Although results from transient gene expression assays showed that MnCl2 treatment upregulated gene translation by approximately 5-fold through the iron response element pathway, immunoblot and reporter assays showed that MnCl2 treatments inhibited protein and gene expression of mACON. This effect was reversed by co-treatment with ferric ammonium citrate. Additional reporter assays with site-directed mutagenesis and electrophoretic mobility-shift assays suggested that a putative metal response element in the promoter of the mACON gene was involved in the regulation of MnCl2 on the gene expression of mACON.</p><p><b>CONCLUSION</b>These findings suggest that manganese acts as an antagonist of iron, disrupting the enzymatic activity and gene expression of mACON and citrate metabolism in the prostate.</p>

Inhibitory effect of manganese on contraction of isolated rat aorta.

The effects of MnCl2 on vascular smooth muscle contraction induced by noradrenaline (NA) and KCl were investigated. Rings segments from rat aorta were isolated and changes in isometric tension recorded. MnCl2 (10 microM and 1 mM) significantly attenuated the contractile responses to NA and KCI. There were also reductions in the contractile responses to CaCl2 in NA- and KCl-stimulated rings, after pretreatment with MnCl2. The magnitude of the phasic contraction to NA was significantly reduced in presence of MnCl2. The results suggest that MnCl2 inhibits vascular smooth muscle contraction by influencing a Ca2+-mediated mechanism.

Effect of manganese toxicity on pigment content, Hill activity and photosynthetic rate of Vigna radiata L. Wilczek seedlings.

Effect of different concentrations, viz. 10(-4) M, 5 x 10(-4) M, 10(-3) M and 5 x 10(-3) M of manganese sulphate (MnSO4, 7H2O) on chlorophyll, carotenoid pigment content and photosynthesis of mungbean seedlings was examined Progressive increase in manganese sulphate concentration upto 5 x 10(-3) M brought about a progressive decrease in total chlorophyll and chl a content. Chl b content changed very little by excess manganese treatment. Total carotenoid pigment content decreased considerably in comparison to control with every concentration of manganese sulphate tried here. Hill activity of chloroplasts isolated from leaves of mungbean seedling and rate of photosynthesis in terms of CO2 uptake showed progressive reduction along with the increase in concentration of the manganese.