1.Interaction between Inorganic Mercury and Selenium on Tissue Sulfhydryl Groups and Glutathione-linked Enzymes in Rats.
Yonsei Medical Journal 1981;22(2):122-126
The effect of selenium on the tissue sulfhydryl group content and lipid peroxide-destorying enzyme system in the liver, kidney and testis of rat treated with mercury was investigated. The male rats were injected s.c. with HgCl2 (10 micromoles/kg BW) and orally received Na2SeO3 (13 micromoles/kg BW) simultaneously. After 3 days, liver, kidney and testis were removed and analyzed. Mercury decreased the total sulfhydryl group content in the kidney by 25% and the total glutathione content in the kidney and testis by 50% and 36%, respectively, with no changes in other tissues. There was 12% increase in the total sulfhydryl group but not in the total glutathione content in kidney by a simul-taneous treatment of Se and Hg. Glutathione peroxidase (GSH-Px) activities were decreased by 63% in the liver and 69% in the kidney, and glutathione reductase (GSH-Rd) activity was increased in the tests by 16% by the Hg treatment with no changes in Other tissues. Hg had no effect upon glutathione-S-transferase activities in all organs examined. Simultaneous Se treatment increased GSH-Rd activity in the kidney by 23% and GSH-Px activities in liver and kidney by 24% and 21%, respectively, compared to the Hg-treated group. These data indicate that the alleviation of Hg toxicity by Se treatment is well correlated with the protein sulfhydryl group content and GSH-Px activity.
Animal
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Glutathione/metabolism*
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Glutathione Peroxidase/analysis
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Glutathione Reductase/analysis
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Male
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Mercury/toxicity*
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Rats
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Selenium/pharmacology*
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Sulfhydryl Compounds/analysis*
2.Gold compound auranofin inhibits I kappaB kinase (IKK) by modifying Cys-179 of IKK beta subunit.
Kye Im JEON ; Mi Sun BYUN ; Dae Myung JUE
Experimental & Molecular Medicine 2003;35(2):61-66
Antirheumatic gold compounds have been shown to inhibit NF-kB activation by blocking IkB kinase (IKK) activity. To examine the possible inhibitory mechanism of gold compounds, we expressed wild type and mutant forms of IKk alpha and beta subunits in COS-7 cells and determined the effect of gold on the activity of these enzymes both in vivo and in vitro. Substitution of Cys-179 of IKK beta with alanine (C179A) rendered the enzyme to become resistant to inhibition by a gold compound auranofin, however, similar protective effect was not observed with an equivalent level of IKK alpha (C178A) mutant expressed in the cells. Auranofin inhibited constitutively active IKK alpha and beta and variants; IKK alpha (S176E, S180E) or IKK beta (S177E, S181E), suggesting that gold directly cause inhibition of activated enzyme. The different inhibitory effect of auranofin on IKK alpha (C178A) and IKK beta (C179A) mutants indicates that gold could inhibit the two subunits of IKK in a different mode, and the inhibition of NF- kB and IKK activation induced by inflammatory signals in gold-treated cells appears through its interaction with Cys-179 of IKK beta.
Amino Acid Substitution
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Animals
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Auranofin/*pharmacology
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COS Cells
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Cysteine/genetics/*metabolism
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Enzyme Activation/drug effects
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Gold Compounds/*pharmacology
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Protein Subunits/chemistry
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Protein-Serine-Threonine Kinases/*antagonists & inhibitors/chemistry/genetics/*metabolism
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Sulfhydryl Compounds/pharmacology
3.Histopathological changes of testes and eyes by neutron irradiation with boron compounds in mice.
Yeon Joo KIM ; Won Ki YOON ; SI Yun RYU ; Ki Jung CHUN ; Hwa Young SON ; Sung Whan CHO
Journal of Veterinary Science 2006;7(1):19-23
This study was performed to investigate the biological effects of boron neutron capture therapy (BNCT) on the testes and eyes in mice using HANARO Nuclear Reactor, Korea Atomic Energy Research Institute. BNCT relies on the high capacity of (10)B in capturing thermal neutrons. Sodium borocaptate (BSH, 75 ppm, iv) and boronophenylalanine (BPA, 750 ppm, ip) have been used as the boron delivery agents. Mice were irradiated with neutron (flux: 1.036739E +09, Fluence 9.600200E+12) by lying flat pose for 30 (10 Gy) or 100 min (33 Gy) with or without boron carrier treatment. In 45 days of irradiation, histopathological changes of the testes and eyes were examined. Thirty-three Gy neutron irradiation for 100 min induced testicular atrophy in which some of seminiferous tubules showed complete depletion of spermatogenic germ cells. Lens epithelial cells and lens fiber were swollen and showed granular changes in an exposure time dependent manner. However, boron carrier treatment had no significant effect on the lesions. These results suggest that the examination of histopathological changes of lens and testis can be used as "biological dosimeters" for gauging radiation responses and the HANARO Nuclear Reactor has sufficient capacities for the BNCT.
Animals
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Boranes/*pharmacology
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Borohydrides/*pharmacology
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Boron Neutron Capture Therapy/*methods
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Eye/pathology/*radiation effects
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Histocytochemistry
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Male
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Mice
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Mice, Inbred C57BL
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Neutrons
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Phenylalanine/*analogs&derivatives/pharmacology
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Seminiferous Tubules/pathology/*radiation effects
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Specific Pathogen-Free Organisms
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Sulfhydryl Compounds/*pharmacology
4.Studies on rat liver nuclear DNA damaged by chemical carcinogen (3'-Me DAB) and AP DNA endonuclease. II. Kinetic properties of AP DNA endonucleases in rat liver chromatin.
Yoon Soo KIM ; Jong Wook KIM ; Seo Eun LEE ; Sang Hwan OH
Journal of Korean Medical Science 1990;5(3):137-143
An experiment was designed to investigate the reaction mechanism of AP (apurinic or apyrimidinic) DNA endonucleases (APcI, APcII, APcIII) purified from rat liver chromatin. Sulfhydryl compounds (2-mercaptoethanol, dithiothreitol) brought about optimal activities of AP DNA endonucleases and N-ethylmaleimide or HgCl2 inhibited the enzyme activities, indicating the presence of sulfhydryl group at or near the active sites of the enzymes. Mg2+ was essential and 4mM of Mg2+ was sufficient for the optimal activities of AP DNA endonucleases. Km values of APcI, APcII and APcIII for the substrate (E. coli chromosomal AP DNA) were 0.53, 0.27 and 0.36 microM AP sites, respectively. AMP was the most potent inhibitor among adenine nucleotides tested and the inhibition was uncompetitive with respective to the substrate. The Ki values of APcI, APcII and APcIII were 0.35, 0.54 and 0.41mM, respectively. The degree of nick translation of AP DNAs nicked by APcI, APcII and APcIII with Klenow fragment in the presence and absence of T4 polynucleotide kinase or alkaline phosphatase were the same, suggesting that all 3 AP DNA endonucleases excise the phosphodiester bond of AP DNA strand to release 3-hydroxyl nucleotides and 5-phosphomonoester nucleotides.
Animals
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Binding Sites
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Chromatin/*enzymology
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DNA Damage/physiology
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DNA Repair/physiology
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DNA-(Apurinic or Apyrimidinic Site) Lyase
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Deoxyribonuclease IV (Phage T4-Induced)
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Endodeoxyribonucleases/antagonists & inhibitors/drug effects/*metabolism
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Kinetics
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Liver/drug effects/*enzymology
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Magnesium/pharmacology
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Rats
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Sulfhydryl Compounds/pharmacology
5.Sulfhydryl modification affects coronary artery tension by changing activity of delayed rectifier K+ current.
Miyong HA ; Sungchoon KWON ; Young Ho LEE ; Dongsoo YEON ; Duck Sun AHN
Yonsei Medical Journal 2000;41(3):372-380
It has been reported that a change in the cellular redox state may be involved in the regulation of vascular tone, but the underlying mechanism is not fully understood. The present study was designed to investigate the cellular effect of sulfhydryl modifying agents in the coronary artery of rabbit using the tension measurement and whole cell clamping method. The application of diamide, a sulfhydryl oxidizing agent, relaxed the endothelium denuded coronary arteries in a dose dependent manner. The fact that this diamide-induced relaxation was significantly attenuated by a pretreatment of 4-AP, and the coronary arteries precontracted with 100 mM K+ instead of histamine, suggests the involvement of 4-AP sensitive K+ channels in the diamide-induced relaxation of coronary arteries. Whole cell patch clamp studies revealed that the 4-AP sensitive IdK was significantly enhanced by the membrane permeant oxidizing agents, diamide and DTDP, and were reversed by subsequent exposure to the reducing agent, DTT. Neither the membrane impermeant oxidizing or reducing agents, GSSG or GSH, had any effect on the activity of IdK, indicating that intracellular sulfhydryl modification is critical for modulating IdK activity. The Diamide failed to significantly alter the voltage dependence of the activation and inactivation parameters, and did not change the inactivation process, suggesting that diamide increases the number of functional channels without altering their gating properties. Since IdK has been believed to play an important role in regulating membrane potential and arterial tone, our results about the effect of sulfhydryl modifying agents on coronary arterial tone and IdK activity should help understand the pathophysiology of the diseases, where oxidative damage has been implicated.
Animal
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Arteries/physiology
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Arteries/drug effects
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Arteries/cytology
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Coronary Vessels/physiology
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Coronary Vessels/drug effects*
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Coronary Vessels/cytology
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Female
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Male
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Oxidants/pharmacology*
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Potassium Channels/physiology
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Rabbits
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Reducing Agents/pharmacology*
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Sulfhydryl Compounds/metabolism*
6.Effects of rutin on oxidative stress in mice with kainic acid-induced seizure.
Marjan NASSIRI-ASL ; E-mail: MNASSIRIASL@QUMS.AC.IR. ; Taghi Naserpour FARIVAR ; Esmail ABBASI ; Hamid Reza SADEGHNIA ; Mehdi SHEIKHI ; Mina LOTFIZADEH ; Parisa BAZAHANG
Journal of Integrative Medicine 2013;11(5):337-342
OBJECTIVEFlavonoids are present in foods such as fruits and vegetables. Several studies have demonstrated a relationship between the consumption of flavonoid-rich foods and prevention of human disease, including neurodegenerative disorders. We assessed the effect of rutin (quercetin-3-O-rutinoside) on oxidative stress in kainic acid (KA)-induced seizure.
METHODSThirty-six BALB/c mice were randomly divided into three groups. In the control group, saline (intra-peritoneal, i.p.) was administered for 7 d, and on the last day, KA (10 mg/kg, i.p.) was injected 30 min after administration of saline. In rutin groups, mice were pretreated with rutin (100 and 200 mg/kg, i.p.) for 7 d, and on the last day, KA (10 mg/kg, i.p.) was injected 30 min after administration of rutin. Subsequently, behavioural changes were observed in mice. Lipid peroxidation and oxidative stress were measured respectively in the early and late phases after KA-induced seizures.
RESULTSSeizure scores in the rutin groups were significantly lower than those in the control group (P < 0.01). Furthermore, rutin dose-dependently inhibited the number of wet-dog shakes (WDS) (P < 0.05). Malondialdehyde level in the hippocampus of the rutin groups was significantly lower than that in the hippocampus of the control group on days 1 and 21 after KA administration. In the rutin groups, the thiol levels observed on day 1 after KA administration were higher than that in the control group (P < 0.01).
CONCLUSIONThese results indicate that rutin has potential anticonvulsant and antioxidative activities against oxidative stress in KA-induced seizure in mice.
Animals ; Dose-Response Relationship, Drug ; Kainic Acid ; toxicity ; Lipid Peroxidation ; drug effects ; Male ; Mice ; Mice, Inbred BALB C ; Oxidative Stress ; drug effects ; Rutin ; pharmacology ; Seizures ; chemically induced ; metabolism ; Sulfhydryl Compounds ; analysis
7.Chelation in metal intoxication XLVI: synthesis of some alpha-mercapto-beta-substituted aryl acrylic acids and their in vitro cadmium chelating ability.
Madhumita CHATTERJEE ; Vinod K DWIVEDI ; Kirti KHANDEKAR ; Sushil K TANDON
Biomedical and Environmental Sciences 2004;17(1):27-32
OBJECTIVETo synthesize some new alpha-mercapto-beta-substituted aryl acrylic acids, characterize them and investigate their in vitro cadmium chelating ability.
METHODSSix alpha-mercapto-beta-substituted aryl acrylic acids were prepared by the alkaline hydrolysis of 5- (aryl methylene) rhodanines, obtained from the condensation of substituted aldehydes and rhodanine following the reported procedure. The new compounds were characterized by elemental analysis, infrared (IR) and nuclear magnetic resonance (NMR) spectroscopy. The liver and kidney from cadmium chloride pre-administered rats were homogenized and their nuclear mitochondrial fraction (NMF) and supernatant cytosol fraction (SCF) were separated. A measured volume of each fraction was dialyzed separately using "dialysis sack" against buffered-KCl medium containing a compound in the final concentration of 1 x 10(-3) mol/L for 3 h at 37 degrees C. The whole content of "sack" was subjected to cadmium estimation following digestion with conc. Nitric acid was detected using flame atomic absorption spectrometer.
RESULTSThe in vitro screening showed that alpha-mercapto-beta-(p-methoxyphenyl) acrylic acid (compound 2) and alpha-mercapto-beta-(m-methoxy, p-hydroxyphenyl) acrylic acid (compound 4) were more effective than alpha-mercapto-beta-thienyl acrylic acid (compound 1) and alpha-mercapto-beta-(p-dimethylaminophenyl) acrylic acid (compound 3) in mobilizing cadmium as their dialyzable chelates. The presence of a methoxy group on the phenyl moiety (compounds 2 and 4) increases the metal chelating ability of mercapto acrylic acids.
CONCLUSIONSCompounds 2 and 4 seem to have accessibility to the cellular system and capability of chelating-out the intracellularly bound cadmium.
Acrylates ; chemical synthesis ; chemistry ; pharmacology ; Animals ; Cadmium Chloride ; metabolism ; toxicity ; Chelating Agents ; chemical synthesis ; chemistry ; pharmacology ; Injections, Intraperitoneal ; Kidney ; drug effects ; metabolism ; Liver ; drug effects ; metabolism ; Male ; Mitochondria ; drug effects ; metabolism ; Mitochondria, Liver ; drug effects ; metabolism ; Rats ; Sulfhydryl Compounds ; chemical synthesis ; chemistry ; pharmacology
8.Effects of tamoxifen citrate on gene expression during nuclear chromatin condensation in male rats.
Mukhtar ALEEM ; Varsha PADWAL ; Jyoti CHOUDHARI ; Nafisa BALASINOR ; Priyanka PARTE ; Manjeet GILL-SHARMA
Asian Journal of Andrology 2005;7(3):311-321
AIMTo evaluate the effects of tamoxifen citrate on gene expression during nuclear chromatin condensation in male rats.
METHODSThe effects of an oral dose of 0.4 kg/(kg.d) tamoxifen citrate on rates of in vitro chromatin decondensation, acridine orange (AO) dye uptake, concentration of thiol-groups, levels and/or expression of transition proteins 1, 2 (TP1, TP2), protamine 1 (P1), cyclic AMP response element modulator-tau (CREMtau), androgen-binding protein (ABP) and cyclic adenosine 3',5' monophosphate (cAMP) were evaluated after 60 days of exposure in adult male rats. Controls received the vehicle.
RESULTSTamoxifen citrate enhanced the rates of chromatin decondensation, increased AO dye uptake and reduced free thiols in caput epididymal sperms and reduced the levels of TP1, TP2, P1, and CREMtau in the testis, while cAMP was unaffected. P1 deposition was absent in the sperm. The transcripts of TP1, TP2 were increased, of P1 and ABP decreased, while those of CREMtau unaffected in the testis.
CONCLUSIONTamoxifen citrate reduced caput epididymal sperm chromatin compaction by reducing the testicular levels of proteins TP1, TP2 and P1 and the CREMtau involved in chromatin condensation during spermiogenesis. Tamoxifen citrate affects the expression of these genes at both the transcriptional and post-transcriptional levels.
Animals ; Base Sequence ; Blotting, Western ; Cell Nucleus ; drug effects ; metabolism ; Chromatin ; metabolism ; Cyclic AMP ; metabolism ; DNA Primers ; Gene Expression ; drug effects ; Male ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction ; Spermatogenesis ; Spermatozoa ; drug effects ; metabolism ; ultrastructure ; Sulfhydryl Compounds ; metabolism ; Tamoxifen ; pharmacology ; Testis ; metabolism ; ultrastructure
9.Effects of the hydro-alcoholic extract of Nigella sativa on scopolamine-induced spatial memory impairment in rats and its possible mechanism.
Mahmoud HOSSEINI ; Toktam MOHAMMADPOUR ; Reza KARAMI ; Ziba RAJAEI ; Hamid Reza SADEGHNIA ; Mohammad SOUKHTANLOO
Chinese journal of integrative medicine 2015;21(6):438-444
OBJECTIVETo evaluate the effect of Nigella sativa (NS) extract on memory performance and its possible mechanisms in scopolamine (Sco)-induced spatial memory impairment model using Morris water maze test.
METHODSThirty-two male Wistar rats were randomly divided into four groups. The control group received saline instead of both NS extract and Sco. The Sco group was treated by saline for two weeks, and was injected by Sco (2 mg/kg, intraperitoneally) 30 min before each trail in Morris water maze test. Sco+NS 200 and Sco+NS 400 groups were daily treated by 200 or 400 mg/kg of NS (intraperitoneally) for two weeks, respectively, and were finally injected by Sco 30 min before Morris water maze test. The brains of animals were removed to determine the acetylcholinesterase (AChE) activity and oxidative stress criteria in cortical tissues.
RESULTSTime latency and path length in the Sco group were significantly higher than in the control group (P<0.01), while the Sco+NS 400 group showed a significantly shorter traveled path length and time latency compared with the Sco group (P<0.01). AChE activity in the cortical tissues of the Sco group was significantly higher than the control group (P<0.01), while AChE activity in the Sco+NS 200 and Sco+NS 400 groups was lower than the Sco group (P<0.01). Following Sco administration, malondialdehyde (MDA) concentrations were increased (P<0.01) in comparison with the control group, while cortical total thiol content decreased (P<0.01). Pretreatment with extracts caused a significant elevation in cortical total thiol content (P<0.01) and reduction in cortical MDA concentration (P<0.01) compared with the Sco group.
CONCLUSIONSHydro-alcoholic extract of NS prevents Sco-induced spatial memory deficits and decreases the AChE activity as well as oxidative stress of brain tissues in rats. Our results support the traditional belief about the beneficial effects of NS in nervous system. Moreover, further investigations are needed for better understanding of this protective effect.
Acetylcholinesterase ; metabolism ; Animals ; Ethanol ; chemistry ; Male ; Malondialdehyde ; metabolism ; Maze Learning ; drug effects ; Memory Disorders ; drug therapy ; physiopathology ; Nigella sativa ; chemistry ; Plant Extracts ; pharmacology ; therapeutic use ; Rats, Wistar ; Reaction Time ; drug effects ; Scopolamine Hydrobromide ; Spatial Memory ; drug effects ; Sulfhydryl Compounds ; metabolism ; Water ; chemistry