1.Studies on the protective effect of metallothionein induction against nephrotoxicity of aminoglycoside antibiotic.
Hae Young CHUNG ; Jung Sun KIM ; Yung Jae RHO ; Jong Seog KIM ; Han Young CHUNG
Korean Journal of Nephrology 1992;11(1):40-48
No abstract available.
Metallothionein*
4.Effects of metallothionein on isolated rat heart.
Zhongdong, SUN ; Jiahong, XIA ; Nianguo, DONG ; Xinling, DU ; Yifan, CHI ; Tienan, YANG ; Chenyuan, YANG
Journal of Huazhong University of Science and Technology (Medical Sciences) 2007;27(4):448-50
To investigate the effects of metallothionein (MT) on isolated rat heart, 16 Wistar rats were randomly divided into 2 groups. In control group (group C), distilled water was injected intraperitoneally and 24 h later isolated hearts were perfused with Langendorff and stored at 4 degrees C for 3 h with histidine-tryptophan-ketoglutarate (HTK) solutions, and then isolated hearts were perfused for 2 h by Langendorff. In experimental group (group E), 3.6% ZnSO(4) was injected intraperitoneally, 24 h later isolated hearts were perfused by Langendorff and stored at 4 degrees C for 3 h with HTK solutions, and then the isolated hearts were perfused for 2 h with Langendorff. MT content, the recovery of hemodynamics, myocardial water content (MWC), lactate dehydrogenase (LDH) and creatine kinase (CK) leakage, adenosine triphosphate (ATP) and malondialdehyde (MDA) content, superoxide dismutase (SOD) activity, myocardial cell Ca(2+) content, Ca(2+)-ATPase activity of mitochondria ([Ca(2+)-ATPase](m)) and its Ca(2+) content ([Ca(2+)](m)), synthesizing ATP activity of mitochondria ([ATP](m)), and the ultrastructure of cells were examined. There were a significant increase in group E in hemodynamic recovery, ATP content, SOD activity, [Ca(2+)-ATPase](m) activity, [ATP](m) activity, and substantial reduction in MWC, LDH and CK leakage, MDA content, myocardial cell Ca(2+) content, [Ca(2+)](m) content, and the ultrastructural injury were obviously milder than that of group C. This study demonstrated that MT has protective effects on isolated rat heart.
Cardiotonic Agents/*pharmacology
;
Creatine Kinase/*metabolism
;
L-Lactate Dehydrogenase/metabolism
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Metallothionein/biosynthesis
;
Metallothionein/*pharmacology
;
Myocardium/*metabolism
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Myocardium/ultrastructure
;
Random Allocation
;
Rats, Wistar
;
Superoxide Dismutase/metabolism
;
Zinc Sulfate/pharmacology
5.Immunohistochemical Study of Metallothionein Expression in Colonic Adenocarcinoma: Correlation with p53, Topoisomerase II-alpha Expression and Apoptosis.
Yong Keum PARK ; Dong In LEE ; Tae Jin LEE ; Jae Hyung YOO
Journal of the Korean Surgical Society 2005;68(5):388-395
PURPOSE: Although immunohistochemically detectable metallothionein (MT) overexpression has been described in proliferation epithelial tumor cells, the clinical significance of the expression remains to be elucidated. Therefore, the present article is focused on evaluating the possible significance of MT expression in colonic adenocarcinoma and its relationship with p53 overexpression, Topoisomerase II-alpha as new cell proliferating marker and apoptosis. METHODS: The following formalin-fixed paraffin embedded surgical or biopsied samples were immunohistochemically stained for MT, p53 and topoisomerase II-alpha, and performed in situ TUNEL method for evaluation of apoptotic cell ; normal control mucosa (78 cases), tubular adenomas (20 cases) and adenocarcinomas with various degree of differentiation (78 cases). RESULTS: The MT immunohistochmical reactivity was decreased in colonic adenocarcinoma than that of normal glandular epithelial and tubular adenoma, with the frequency of MT expression in colonic adenocarcinoma depending upon tumor differentiation only. But the frequency of p53 expression was correlated with T-stage, lymph node metastasis and clinical staging, while topoisomerase II-alpha expression and apoptosis in colonic adenocarcinoma were correlated with lymph node metastasis and clinical staging. The immunohistochemical expression of MT and p53 expression in colonic adenocarcinoma was inversely correlated. Also, the inverse correlation between MT expression and expression of toposiomerase II-alpha indices and apoptotic indices were noted. CONCLUSION: These data suggest that MT expression may play a role in proliferative activity and apoptosis in colonic adenocarcinoma. Although MT expression is correlated to tumor differentiation, further studies of a possibility of prognostic factor, such as p53, are required for the determination of significant relationships in other clinicinopathologic indices.
Adenocarcinoma*
;
Adenoma
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Apoptosis*
;
Colon*
;
In Situ Nick-End Labeling
;
Lymph Nodes
;
Metallothionein*
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Mucous Membrane
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Neoplasm Metastasis
;
Paraffin
6.Metallothionein induction and its protective effect in liver and kidney of rats exposed to cadmium chloride.
Nam Song KIM ; Jae Hyung LEE ; Dai Ha KOH ; No Suk KI ; In Dam HWANG
Korean Journal of Preventive Medicine 1991;24(3):287-304
Tolerance to several toxic effects of cadmium, including lethality has been shown following pretreatment with cadmium and zinc. This study was designed to determine if tolerance also develops to Cd-induced hepatotoxicity and renal toxicity. Three groups of rats (A, B, C), each consisting of 16 rats, were studied and each group was divided into four subgroups (1, 2, 3, 4), 4 rats for each subgroup. Rats were subcutaneously pretreated with saline (A), CdCl2(0.5 mg/kg, B), and ZnCl2 (13.0 mg/kg, C) during time periods of 1~6 weeks. At the end of the period, rats were challenged with CdCl2 (3.0, 6.0 and 9.0 mg/kg, ip). After giving the challenge dose, cadmium and metallothionein (MT) concentrations were determined and also observed the histologic change in liver and kidney. The concentration of cadmium in liver and also observed the increased dose-dependently to the challenge dosage. These data indicate the kidney is a major target organ of chronic cadmium poisoning, and suggest that cadmium induced hepatic injury, via release of Cd-MT, may play and important role in the nephrotoxicity observed in response to long-term exposure to cadmium. In addition, histologic examination of group A2, A3 and A4 revealed moderate to severe cadmium toxicity, evidenced by infiltration of inflammatory cells, cell swelling, pyknosis, enlarged sinusoids and necrosis in liver, and tubule cell necrosis and degeneration in kidney. However, MT concentrations in liver and kidney were increased by the pretreatment of CdCl2 and ZnCl2 and their morphological findings were not significantly changed, comparing with control group. Higher MT concentration in liver and kidney observed in the pretreated groups constitutes a plausible explanation of the protective effects of pretreatment against the cadmium toxicity after challenge dosing.
Animals
;
Cadmium Chloride*
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Cadmium Poisoning
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Cadmium*
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Kidney*
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Liver*
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Metallothionein*
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Necrosis
;
Rats*
;
Zinc
7.The Effect of Metallothionein on the Resistance to Cisplatin in Transfected Mouse NIH/3T3 Cells.
Myung Hee SOHN ; Jae Yong KWAK ; Chang Yeol YIM
Journal of the Korean Cancer Association 1997;29(4):576-583
PURPOSE: Metallothionein is an intracellular cystein-rich thiol-containing protein. Increased metallothionein content in tumor cells has been suggested to be a mechanism of resistance to cisplatin. In most of previous studies evaluating the role of metallothionein in cisplatin resistance, tumor cells were usually exposed to cadmium to increase metallothionein content. Therefore, cisplatin resistance of the cells may be related to cadmium exposure itself, which induces various changes in cell characteristics, but not to increased metallothionein content. The purpose of this study is to evaluate the role of metallothionein content alone in cellular resistance to cisplatin without exposure of cells to cadmium. MATERIALS AND METHOD: We measured the toxicity of cisplatin in mouse NIH/3T3 cells that vary in their content of metallothionein as a consequence of transfection with a plasmid that result in the constitutive expression of metallothionein. MT cells were derived from NIH/3T3 cells by transfection with a plasmid containing the genome of bovine papilloma virus and the mouse metallothionein-I, derived by the promoter for the glucose-regulated protein of 78kD. Control cells were similary transfected with bovine papilloma virus-based plasmids with the gene for metallothionein inverted and thus separated from the promoter (TM), or deleted, along with promoter (BPA). The number of copies of the plasmid were similar in each kind of transfected cells. Expression of metallothionein required neither selection nor maintenance of cells in the presence of heavy metals. RESULTS: Synthesis of metallothionein was 15-fold greater in the MT cells than in the TM or BPA cells. The concentration of cisplatin sufficient to reduce the cells per well by one-half (IC-50) was 0.40+/-0.075 uM in MT cells. In TM and BPA cells, it was 0.36 0.035 uM and 0.423+/-0.032 uM. There were no significant differences in IC-50 between three cell lines. CONCLUSION: In spite of large differences between MT and control cells in their cellular content of metallothionein, no differences in resistance to cisplatin were observed.
Animals
;
Cadmium
;
Cell Line
;
Cisplatin*
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Genome
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Metallothionein*
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Metals, Heavy
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Mice*
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Papilloma
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Plasmids
;
Transfection
8.Effect of Sodium Selenite on Metallothionem Induction by the Treatment of Mercuric Chloride to Rats.
Yo Hwan YANG ; Hyo Min LEE ; Dong Chun SHIN ; Yong CHUNG
Korean Journal of Occupational and Environmental Medicine 1989;1(2):236-259
This study was conducted to investigate the metallothionein induction by sodium selenite in mercuric Chloride intoxication. Mercuric chloride of 3.0 mg/kg of body weight was administered simultaneously with sodium selenite of either a high dosage of 2.5 mg/kg or low dosage of 1mg/kg via intraperitioneal injecion to rats. After the treatment, 6, 12, 24 and 72 hours later, mercury and selenium content in liver and kidney tissues, serum transaminase activities(SGOT, SGPT), metallothionein, glutathione, glutathione peroxidase sotivity and histological changes were determined. The results were summarized as follows on: 1. The combined administration of mercury and selenium significantly more decreased mercury concentrations in liver and kidney compared to the administration of mercury only. 2. The combined administration of mercury and selenium significantly more increased renal metallothionein compared to administration of mercury only. This phenomenon was more remarkable when a large dose(2.5 mg/kg) of selenium was administered with mercuric chloride. 3. Glutathione concentration, glutathione peroxidase activity in liver and kidney and serum transaininase activity(SGOT, SGPT) were less suppressed in the combined administration group than the mercury only group. 4. Histological damage in renal tissue was not revealed in rats treated with mercury and selenium. From the above results, selenium administered simultaneously with mercury decreased mercury concentration in liver and kidney, increased renal metallothionein concentration and decreased the toxicity of mercury. The hypothetic mechanism suggested is that selenium induces the metallothionein combined with Hg and redistributes Hg in tissues.
Animals
;
Body Weight
;
Glutathione
;
Glutathione Peroxidase
;
Kidney
;
Liver
;
Mercuric Chloride*
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Metallothionein
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Rats*
;
Selenium
;
Sodium Selenite*
;
Sodium*
9.Induction Of Metallothionein And Toxicity In Acute Cadmium Intoxicated Rat.
Kyung Joon MIN ; Jung Duck PARK ; Yeon Pyo HONG ; Im Won CHANG
Korean Journal of Preventive Medicine 1993;26(2):231-250
Thirty five male Sprague-Dawley rats were treated with cadmium chloride solution ranging from 0.2 to 3.2mg CdCl2/kg by intravenous single injection. At 48 hours after administration of cadmium, total cadmium, MT bound cadmium and histopathologic finding in liver, kidney, lung, heart, testis, metallothionein in liver, kidney and total cadmium in blood were examined. Tissue cadmium concentration was highest in liver, followed by in kidney, heart, lung and testis. Cadmium bound to metallothionein(MT-Cd) and ratio of MT-Cd to total cadmium were increased in liver and kidney dependently of cadmium exposure dose, but not significantly changed in other organs. On histopathologic finding, the most susceptible organ was heart in considering cadmium exposed dose, but testis in considering cadmium concentration. Blood cadmium concentration was increased with dose-dependent pattern, and significantly correlated with tissue cadmium concentration, so that we may estimate tissue cadmium concentration by measurement of blood cadmium concentration. Metallothionein in liver and kidney was increased with dose-dependent pattern, higher in liver than in kidney, and was significantly correlated with tissue cadmium concentration. However, metallothionein induction efficiency of tissue cadmium(microgram MT/microgram Cd) was greater in liver than in kidney, and reverse to tissue concentration or exposed dose of cadmium.
Animals
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Cadmium Chloride
;
Cadmium*
;
Heart
;
Humans
;
Kidney
;
Liver
;
Lung
;
Male
;
Metallothionein*
;
Rats*
;
Rats, Sprague-Dawley
;
Testis
10.Role of Inducibility of Superoxide Dismutases and Metallothionein of Mouse Lungs by Paraquat in Aging.
Tae Bum LEE ; Yoo Hwan PARK ; Cheol Hee CHOI
Tuberculosis and Respiratory Diseases 2001;50(5):579-590
BACKGROUND: The aging process may be induced, at least in part, by reactive oxygen species(ROS). It has been though that the lung could be a good source of ROS because it has a high oxygen tension. In the present study, we invetigated the inducibility of the first and last lines against oxidative stress, superoxide dismutases (Cu/Zn-SOD and Mn-SOD) as a scavenger of O2- and metallothionein(MT) as a scavenger of OH·, respectively, in mouse lungs with age. METHODS: Oxidative stress was induced by paraquat, an intracellular superoxide generator, at 1, 4, 8, and 12 months of age and then SODs and MT mRNAs were determined by RT-PCR method. RESULTS: The steady-state level of Mn-SOD mRNA increased from 1 to 8 months but decreased thereafter. However, Mn-SOD mRNA was not induced by paraquat after 1 month. On the other hand, there was no change in the steady-state level of Cu/Zn/-SOD mRNA, which decrease abruptly at 12 months of age. Additionally, Cu/Zn/-SOD mRNA was not induced by paraquat at any age. There was no change in the steady-state level of MT mRNA with age whereas its inducibility by paraquat was intact at all ages. CONCLUSION: These results indicate that lack of induction of SODs with age may be one of the causative factors in the aging process while induction of MT may play an important role in the defense against oxidative stress. It is therefore implicated that the tissue antioxidant/proxidant balance could be one determinants of meal life span.
Aging*
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Animals
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Hand
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Lung*
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Meals
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Metallothionein*
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Mice*
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Oxidative Stress
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Oxygen
;
Paraquat*
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RNA, Messenger
;
Superoxide Dismutase
;
Superoxides*