• BMB Reports
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• v.56 no.2
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• pp.96-101
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• 2023

Particulate matter is an air pollutant composed of various components, and has adverse effects on the human body. Particulate matter is known to induce cell death by generating an imbalance in the antioxidant system; however, the underlying mechanism has not been elucidated. In the present study, we demonstrated the cytotoxic effects of the size and composition of particulate matter on small intestine cells. We found that particulate matter 2.5 (PM_2.5) with extraction ion (EI) components (PM_2.5 EI), is more cytotoxic than PM containing only polycyclic aromatic hydrocarbons (PAHs). Additionally, PM-induced cell death is characteristic of ferroptosis, and includes iron accumulation, lipid peroxidation, and reactive oxygen species (ROS) generation. Furthermore, ferroptosis inhibitor as liproxstatin-1 and iron-chelator as deferiprone attenuated cell mortality, lipid peroxidation, iron accumulation, and ROS production after PM_2.5 EI treatment in human small intestinal cells. These results suggest that PM_2.5 EI may increase ferroptotic-cell death by iron accumulation and ROS generation, and offer a potential therapeutic clue for inflammatory bowel diseases in human small intestinal cells.

• Journal of Soil and Groundwater Environment
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• v.14 no.2
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• pp.26-32
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• 2009

In this study, the degradation of BTEX (benzene, toluene, ethylbenzene, xylene) was tested in both (Fe$^{3+}$+chelating agent)/H$_2$O$_2$system [Fe(III) 1 mM, oxalate 6 mM, H$_2$O$_2$ 3%, and pH 6] and UV/(Fe3++ chelating agent)lHzOz system [UV dose 17.4 kWhlL, Fe(III) 1mM, oxalate 6 mM,H$_2$O$_2$ 1%, and pH 6]. The types of chelating agents used in experiments were catechol, NTA, gallic, acetyl acetone, succinic, acetate, EDTA, citrate, malonate, and oxalate and the optimum chelating agent for BTEX degradation was determined. The results showed that acetate was the optimum chelating agent for BTEX degradation in both (Fe$^{3+}$+chelating agent)/H$_2$O$_2$ and UV/(Fe$^{3+}$+chelating agent)/H$_2$O$_2$ system, and UV radiation enhanced the degradation of BTEX with any types of chelating agents. Moreover, UV/(Fe$^{3+}$+chelating agent)/H$_2$O$_2$ system, which chelating agent was acetate, removed effectively mixtures of BTEX and MTBE (methyl tert-butyl ether) when the concentration of both BTEX and MTBE was 200 mg/L, respectively. In this system, BTEX was degraded completely and 85% of MTBE was degraded at the reaction time of 180 min. Therefore, UV/((Fe$^{3+}$+chelating agent)/H$_2$O$_2$ system with acetate as a chelating agent removed not only BTEX but also BTEX and MTBE, effectively.

• Journal of Soil and Groundwater Environment
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• v.12 no.2
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• pp.27-36
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• 2007

A recent study showed that MTBE can be degraded by Fenton's Reagent (FR). The treatment of MTBE with FR, however, has a definite limitation of extremely low pH requirement (optimum pH $3{\sim}4$) that makes the process impracticable under neutral pH condition on which the ferrous ion precipitate forming salt with hydroxyl anion, which result in the diminishment of the Fenton reaction and incompatible with biological treatment. Consequently, this process using only FR is not suitable for in-situ remediation of MTBE. In order to overcome this limitation, modified Fenton process using NTA, oxalate, and acetate as chelating reagents was introduced into this study. Modified Fenton reaction, available at near neutral pH, has been researched for the purpose of obtaining high performance of oxidation efficiency with stabilized ferrous or ferric ion by chelating agent. In the MTBE degradation experiment with modified Fenton reaction, it was observed that this reaction was influenced by some factors such as concentrations of ferric ion, hydrogen peroxide, and each chelating agent and pH. Six potential chelators including oxalate, succinate, acetate, citrate, NTA, and EDTA were tested to identify an appropriate chelator. Among them, oxalate, acetate, and NTA were selected based on their remediation efficiency and biodegradability of each chelator. Using NTA, the best result was obtained, showing more than 99.9% of MTBE degradation after 30 min at pH 7; the initial concentration of hydrogen peroxide, NTA, and ferric ion were 1470 mM, 6 mM, and 2 mM, respectively. Under the same experimental condition, the removal of MTBE using oxalate and acetate were 91.3% and 75.8%, respectively. Optimum concentration of iron ion were 3 mM using oxalate which showed the greatest removal efficiency. In case of acetate, $[MTBE]_0$ decreased gradually when concentration of iron ion increased above 5 mM. In this research, it was showed that modified Fenton reaction is proper for in-situ remediation of MTBE with great efficiency and the application of chelatimg agents, such as NTA, was able to make the ferric ion stable even at near neutral pH. In consequence, the outcomes of this study clearly showed that the modified Fenton process successfully coped with the limitation of the low pH requirement. Furthermore, the introduction of low molecular weight organic acids makes the process more available since these compounds have distinguishable biodegradability and it may be able to use natural iron mineral as catalyst for in situ remediation, so as to produce hydroxyl radical without the additional injection of ferric ion.

• The Korean Journal of Pharmacology
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• v.27 no.2
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• pp.155-166
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• 1991

In order to evaluate a potential role of mitochondria in the mediation of toxicity of paraquat (PQ), submitochondrial particle and microsome of mouse liver were compared by oxygen radical generation and lipid peroxidation. With NADH in submitochondrial particle and NADPH in microsome as electron donors, PQ stimulated production of superoxide anion and $H_2O_2$ in both fractions. Under the same conditions, PQ enhanced the generation of ethylene from methional suggestiong stimulation of OH production by PQ. But these effects by PQ were somewhat lower in submitochondrial particle than in microsome. In addition, lipid peroxidation(measured as MDA production) was stimulated by PQ in both fractions. The stimulation of lipid peroxidation in both fractions seemed to occur by the same mechanism probably through perferryl ion. This was supported by the following findings: i) The lipid peroxidation in both fractions was partially inhibited by SOD and completely inhibited by DETAPAC(an iron chelator) but not by catalase or OH scavenger. ii) Addition of $ADP-Fe^{3+}$ further increased PQ-induced lipid peroxidation but decreased ethylene production from methional suggesting no correlation between OH production and lipid peroxidation. The redox-cycling of PQ in mitochondria appeared to be linked to NADH dehydrogenase, not to CoQ since all of the observed stimulations by PQ in submitochondrial particle were inhibited by p-hydroxymercuribenzoate(a NADH dehydrogenase inhibitor) but not affected by other respiratory chain blockers. The above results demonstrate that redox-cycling properties of PQ leading to oxygen radical generation and lipid peroxidation can also occur in mitochondria in the same manner as in microsome. Therefore, the observed actions of PQ in mitochondria suggest that mitochondria may also contribute to toxicity of this drug in vivo.

• Tuberculosis and Respiratory Diseases
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• v.42 no.2
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• pp.184-205
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• 1995

Background: Pulmonary toxicity by bleomycin has multiple mechanisms including direct tissue toxicity due to oxygen-derived free radicals and indirect toxicity through amplification of pulmonary inflammation. To evaluate the effect of chelators or free radical scavenger to lung damage induced by bleomycin, penicillamine as a copper chelator, deferoxamine as an iron chelator and vitamin E as a free radical scavenger were administered. Methods: Two hundred Wistar rats were divided into five groups: Control, bleomycin treated, bleomycin-penicillamine treated, bleomycin-deferoxamine treated, and bleomycin-vitamin E treated groups. Rats sacrificed on day 1, day 3, day 4, day 7, day 14, and day 28 after treatment. Bronchoalveolar lavage, light microscopic and immunohistologic studies for type I, III, IV collagens, fibronectin, laminin and NBD phallicidin were evaluated. Results: There was a significant increase in the total cell counts of bronchoalveolar lavage on day 1 from all treated animals and vitamin treated group showed an abrupt decrease in total cell counts with decrease of neutrophils on day 3. Bleomycin-vitamin E treated group had the least histologic changes such as pulmonary fibrosis. The alveolar basement membranes were positive for type IV collegen and laminin. Basement membranes of bleomycin, bleomycin-penicillamine, or bleomycin-deferoxamine treated groups were disrupted and fragmented on day 4 or 7. The bleomycin-vitamin E treated group had intact basement membranes until day 28. Conclusion: Bleomycin-induced pulmonary fibrosis was related to the severity of acute injury to oxygen radicals or activation of neutrophils and disruption of basement membrane. Vitamin E seemed to be the most effective antioxidant in the inhibition of bleomycin-induced pulmonary injury and fibrosis.

• Applied Microscopy
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• v.39 no.4
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• pp.355-363
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• 2009

The purpose of this study was to demonstrate the effect of Momordica Charantia L. water extracts, one of the natural chelator, on the biochemical and enzyme activity changes in the rats liver and kidney caused by lead acetate. Rat approximately 250 g in weight were grouped into the control, lead acetate treated, and the Momordica Charantia L. boiling water extracts treated after lead acetate groups. Lead acetate (1,000 ppm) and Momordica Charantia L. water extracts (5%, 10%) were delivered drinking water. Serum AST, ALT and BUN were measured, histological alteration of liver and kidney were examined by light microscopy. Momordica Charantia L. extract group was decreased serum AST, ALT and BUN level induced by lead. Optical observations of liver tissue, lead group were observed necrosis of hepatic cells and infiltration of inflammatory cells, but Momordica Charantia L. extract group was observed only slight infiltration of inflammatory cells around the central vein. Optical observations of kidney tissue, lead acetate induced atrophy and necrosis of glomerulus and infiltration of inflammatory cell around renal tubule. For the group treated with Momordica charantia L. extract, the glomerulus was similar to the control, some around the renal tubule was observed infiltration of inflammatory cells. In conclusion, Momordica Charantia L. water extract may protect the lead-induced toxicity on liver and kidney.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.3 no.2
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• pp.59-64
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• 2017

It has been reported that $^{64}Cu$ was radiolabeled with bombesin (BBN) peptide binding to the gastrin releasing peptide receptor expressed in human prostate cancer cells (PC3), confirming tumor target efficacy in mouse model. In this study, we developed the kit for the diagnosis and treatment of prostate cancer that can be used clinically using bombesin peptide available of $^{64}Cu$ and $^{177}Lu$ radioisotope labeling. The NODAGA-galacto-BBN peptide containing the NODAGA chelator and galactose was dispensed into a sterilized glass vial and lyophilized to prepare a kit. The stability of the kit after long-term storage in the $4^{\circ}C$ cold chamber and the radiolabeling efficiency after $^{64}Cu$ or $^{177}Lu$ labeling were confirmed by thin layer chromatography. When labeling with $^{64}Cu$ at the initial stage of storage, labeling efficiency of NODAGA-galacto-BBN peptide kit was over 96%, labeling efficiency was over 90% when $^{177}Lu$ was labeled. At 11 months after storage, the radiolabeling efficiency of kit against $^{64}Cu$ and $^{177}Lu$ was each over 95% and 90%. The cell viability was significantly reduced in the $^{177}Lu$-NODAGA-galacto-BBN treated group compared with the control and $^{177}Lu$ alone treated group in clonogenic assay. In conclusion, the NODAGA-galacto-BBN kit prepared by the lyophilization showed high stability over time and high yield of radioisotope labeling. Also $^{177}Lu$-NODAGA-galacto-BBN confirmed high cytotoxicity to prostate cancer cells. Therefore, the NODAGA-galacto-bombesin kit is expected to be useful for the diagnosis and treatment of prostate cancer patients.

• Journal of Radiation Protection and Research
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• v.22 no.1
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• pp.9-14
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• 1997

Chitosan, a natural nontoxic chelator, was reported to reduce whole body retention of radiostrontium in mice. As calcium has a simillar chemical properties to strontium both of which be easily bound with hydroxyapatite structure, calcium can be either a competitor or enhancer to chitosan on the removal of radiostrontium. We compared the effect of chitosan and calcium on the excretion of ingested radiostrontium ($^{85}$Sr). Chitosan or calcium($Cacl_2$) and usual food was mixed as 1:99 by weight. The mixed food to chitosan (group 1) or calcium (group 2) were given orally for 30 days before $^{85}$Sr administration. In other groups, mixed calcium and chitosan solution (group 3), 1% calcium (group 4), or 1% chitosan solution (group 5) was given for 7 days immediately after oral administration of $^{85}SrC1_2$ ($0.25{\mu}Ci$). In control group, no chitosan or calcium were given. Either chitosan or calcium was effective on the removal of $^{85}Sr$ from mouse body(Table. 1). Addition of calcium on chitosan did not improve or deteriorate the effect of chitosan on the removal of $^{85}Sr$ from mouse body. In conclusion, calcium was similarly effective on the removal of $^{85}Sr$ from mouse body.

• Toxicological Research
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• v.23 no.1
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• pp.33-38
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• 2007

Zinc is an endogenous transition metal that can be synaptically released during neuronal activity. However, zinc may contribute to the neuropathology associated with a variety of conditions. Carnosine expressed in glial cells can modulate the effects of zinc on neuronal excitability as a zinc chelator. We hypothesize that carnosine may protect against neurotoxicity of zinc in cortical neuronal cells. The cortical neuronal cells from newborn rats were prepared and exposed to zinc chloride and/or carnosine at various concentrations. Zinc at the doses of 0 to $500{\mu}M$ decreased neuronal cell viability in a dose-dependent manner. Additionally, at the concentrations of 100 and $200{\mu}M$, it significantly decreased cell viability in an exposed time-dependent manner (p < 0.05). Treatment with carnosine at the concentrations of 20 and $200{\mu}M$ significantly increased neuronal cell proliferation by approximately 14% and 20%, respectively, compared to the control (p < 0.05). At the concentrations of 100 and $200{\mu}M$ zinc, $20{\mu}M$ carnosine significantly increased the viability of neuronal cells by 18.3% and 12.1 %, and $200{\mu}M$ carnosine also increased it by 33.5% and 28.6%, respectively, compared to the normal control group (p < 0.01). These results suggest that carnosine at a physiologically relevant level may protect against zinc-mediated toxicity in neuronal cells as an endogenous neuroprotective agent.

• The Korean Journal of Pharmacology
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• v.24 no.1
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• pp.111-123
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• 1988

Neutrophil elastases were purified by a three step procedure consiting of one Sephadex G-75 and two HPLC elutions. The elastases cross-reacted with antibodies to human neutrophil elastase. Three bands with molecular weights between 26,000 and 29,700 were observed by gel electrophoresis. At each stage of purification the quantity of Zn increased, reaching molar ratio of 2:1 with elastase in the most purified samples. Calcium content. was seletively elevated during the earlier stages of purification but decreased to a ratio of 0.25 to 1 with elastase at the final step of purfication. Neutrophil elastase could be inhibited by EDTA, EGTA and 1,10-phenanthroline. EGTA inhbition was noncompetitive inhibition and reversible only if the time of preincubation was relatively short, indicating the instability of the apoenzyme. The concentration of chelator required to show significant inhibition of elastase was also dependent upon the stage of purity and the ionic strength of the reaction mixture. Inhibition by EGTA, followed by the removal of EGTA, could be reversed by Zn. In the presence of EGTA the enzyme could be returened to full activity by the addition of Zn, Mn and Ca, but not Mg or Na. All of the above evidence strongly supports human neturophil elastase could be a metalloenzyme as well as a serine protease.