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Volume 51 , Issue 3
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REVIEW
  • Tomoyuki Terada
    Volume 51 (2005) Issue 3 Pages 263-271
    Released: June 01, 2005
    JOURNALS FREE ACCESS
    The polymorphic expression of glutathione S-transferase (GST) in animal lenses has been demonstrated by purification with affinity chromatography, immunochemical analysis with Western-blotting and amino acid sequencing of the N-terminal regions. Three major classes of GST (class α, γ or π) have been identified in human, bovine, pig, rabbit, rat and guinea pig. They show a typical GSH-conjugation reaction with various chemicals, including organic peroxides. These GSTs possess unique properties against oxidative stress, that is, α-class GST exhibits a GSH-peroxidase-like activity, μ-class GST shows a potent resistance to naphthoquinone and H2O2, and π-class GST shows a high sensitivity to a variety of oxidants. Because the oxidative stress is believed to be a major factor in the development of cataracts, these unique expression patterns of GST in animal lenses reveal an important factor in the formation and development of oxidant-induced cataracts, including naphthalene cataract and senile cataract. The most typical example has been presented that effect of curucumin on the prevention of cataract through the induction of GST. This review summarizes the evidence for the involvement of GST in cataractogenesis, which may be seen to support it as an important risk.
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MINIREVIEW
  • Kenichiro Nakashima
    Volume 51 (2005) Issue 3 Pages 272-277
    Released: June 01, 2005
    JOURNALS FREE ACCESS
    Recently, drug abuse has become a serious social problem world wide. In Japan, methamphetamine (MP) is the most popular drug of abuse. In addition to MP, the use of 4,5-methylenedioxymethamphetamine (MDMA), called ecstacy, is rapidly increasing, especially among young people. The development of simple and convenient analytical methods for the analysis of these drugs of abuse is necessary for the prediction of and protection from human health risks. Many useful methods have been developed for qualification and quantification of drugs of abuse. Among these, gas chromatography with mass spectrometry (MS) and high-performance liquid chromatography with MS (HPLC-MS or LC-MS) or fluorescence (HPLC-FL) detection are widely used. As highly sensitive methods, precolumn or postcolumn derivatization methods are commonly utilized in HPLC. This review focuses on HPLC methods used for the practical analysis of drugs of abuse, mainly for amphetamine derivatives and MDMAs in biologic samples such as urine, blood, and hair.
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REGULAR ARTICLES
  • Eiichi Mikami, Tomomi Goto, Tsutomu Ohno, Hisao Oka, Hisayuki Kanamori
    Volume 51 (2005) Issue 3 Pages 278-283
    Released: June 01, 2005
    JOURNALS FREE ACCESS
    A high performance liquid chromatography (HPLC) method for the simultaneous analysis of the seven benzodiazepines (BZDs), oxazolam, nitrazepam, oxazepam, tofisopam, triazolam, clotiazepam and diazepam (DIA) is presented for application in the screening examination of dietary supplements as adulterants. Samples were analyzed after extraction with methanol. HPLC analysis was performed with on a column of Wakosil 5C18 (4.6 × 150 mm, 5 μm) with the mobile phase consisting of 1-heptanesulfonic acid sodium salt 5 mM dissolved in water/acetonitrile 1000 ml (13 : 7, v/v), adjusted with phosphoric acid to pH 2.4. The column eluent was monitored with a photodiode array detector, and the quantitative analysis of BZDs was performed at 225 nm. The calibration curves of the seven BZDs showed good linearity and the correlation coefficients were better than 0.999 in all cases. When this procedure was applied to commercial supplements, an DIA-adulterated capsule-type supplement was detected. Finally, DIA was identified and determined using a combination of three different analytical methods: HPLC/photodiode array, thin-layer chromatography (TLC), and LC/MS. DIA was present at a concentration of 1.9 mg/capsule. The procedure described here can provide a broad analysis in a single run within 17 min and is available for the screening of seven BZDs in adulterated supplements with minimal sample preparation.
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  • Heekyung Bae, Seong Sook Nam, Hyoung-Sook Park, Kwangsik Park
    Volume 51 (2005) Issue 3 Pages 284-290
    Released: June 01, 2005
    JOURNALS FREE ACCESS
    Metallothioneins (MTs) are inducible metal-binding proteins characterized by low molecular weight (6000-10000 Da) and play a major role in detoxification of heavy metals. They are known to be induced by heavy metals in various organs of different species and represent a potential biomarker of aquatic contamination with heavy metals. In this study, cloning and sequencing of a MT gene of the Korean freshwater fish, the crucian carp (Carassius auratus), were performed. Furthermore, the gene expression and cadmium accumulation in the gills of the crucian carp were compared during the cadmium exposure period of 25 days. The MT gene, lacking the 5′ promoter region, is 405 bp long and has a tripartite structure consisting of three exons and two introns. The open reading frame encodes a cysteine-rich (20 cysteines) polypeptide of 60 amino acids containing six Cys-X-Cys motifs, typically found in this protein family. It was found that the expression of MT mRNA of gills was very low in normal control fish but high mRNA expression was induced after 1-day exposure to cadmium. However, the mRNA levels decreased after 1 day even though the cumulative cadmium concentration increased during the remaining exposure period. These results suggest that MT expression does not always reflect the cadmium accumulation in the gills of the fish and may have limitations in its use as a biomarker to monitor cadmium contamination of aquatic environments.
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  • Uchenna Chinedu Ozumba, Nwora Abiodun Ozumba, Samuel Anya
    Volume 51 (2005) Issue 3 Pages 291-293
    Released: June 01, 2005
    JOURNALS FREE ACCESS
    This prospective study was carried out between July and December 2000 at the University of Nigeria Teaching Hospital (UNTH), to determine the species and prevalence of intestinal helminthes in pregnant women attending antenatal clinics. A total of 161 stool samples were collected from the women. The samples were examined by the kato thick smear technique. For each stool sample, two kato slides were made and the average of the total number of eggs was taken. The prevalence of helminthic infection was 11.8% with only Ascaris lumbricoides (8.7%) and Trichuris trichuria (3.1%) being detected. The intensity of infection was generally high with a geometric mean intensity of 50.1 eggs per gm of faeces. About 11.8% of cases were multiple infections. There was no significant difference between the mean haemoglobim levels in both the infected pregnant women and the non-infected pregnant women. The poor socioeconomic status of the women coupled with poor environmental sanitation and lack of clean portable water supply contributed to the high prevalence of these parasites.
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  • Fumihiko Katagiri, Shin Inoue, Yuhki Sato, Hiroki Itoh, Masaharu Takey ...
    Volume 51 (2005) Issue 3 Pages 294-299
    Released: June 01, 2005
    JOURNALS FREE ACCESS
    Lansoprazole, a proton pump inhibitor (PPI), is widely used in the treatment of peptic ulcer, gastroesophageal reflux disease and eradication of Helicobacter pylori. Lansoprazole has been reported to be a PPI with mucosal protective action. However, except for inhibition of gastric acid secretion, its mechanism of action is not well understood. We therefore examined the effects of lansoprazole on plasma levels of gastrointestinal peptides (gastrin, somatostatin, motilin, vasoactive intestinal peptide [VIP], substance P, and calcitonin gene-related peptide [CGRP]). Lansoprazole 30 mg or placebo was orally administered to five healthy male volunteers aged 25-30 years. Venous blood samples were taken before and 30, 60, 90, 120, 180, 240, and 360 min after administration. Plasma peptide levels were measured using a sensitive enzyme immunoassay. Compared with the response of the placebo treated group, lansoprazole caused significant (p < 0.05) increases in somatostatin-, VIP-, substance P- and CGRP-like immunoreactive substance (IS) levels at 120, 120, 90-240, and 120 min, respectively. Furthermore, lansoprazole significantly suppressed temporary elevation (30 min) of placebo gastrin-IS levels. But lansoprazole had no effect on plasma motilin-IS levels compared with the placebo. In this study, lansoprazole raised somatostatin-IS levels and inhibited the increase in gastrin-IS levels. On the other hand, lansoprazole raised substance P- and CGRP-IS levels. Recently, capsaicin-sensitive afferent nerves have been shown to play an important role in gastric mucosal defensive mechanisms. Capsaicin stimulates afferent nerves and enhances the release of CGRP and substance P in the stomach. We hypothesize that lansoprazole might not only potently inhibit gastric acid secretion but also exert gastroprotective actions via capsaicin-sensitive afferent nerves.
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  • Ferah Sayim, Nefise Ülkü Karabay Yavasoglu, Yigit Uyanikgil, ...
    Volume 51 (2005) Issue 3 Pages 300-307
    Released: June 01, 2005
    JOURNALS FREE ACCESS
    Cypermethrin is a synthetic pyrethroid that belongs to a group of insecticides with low mammalian toxicity but high insecticidal activity. The present study was undertaken to evaluate subacute toxicity of orally administered cypermethrin in rats based on the haematological, enzymological, and histological brain examination. The study was conducted on 8-week old male Wistar rats and Kral 250 EC (250 g of cypermethrin/l) was orally administered (60, 150, and 300 mg/kg) for 28 consecutive day. Thus, the investigation covered four groups of animals: three experimental groups and one control group, of 20 rats each. Our results demonstrated that experimental groups receiving both 150 and 300 mg/kg cypermethrin treatment led to significant dose-dependent decrease in some haematological parameters [red blood cell (RBC) counts, haematocrite (Ht), thrombocyte, and mean corpuscular haemoglobin (MCH) values] at the end of the experiment. When compared with control animals, there were significant increases between initial body weights and final body weights of cypermethrin treated rats, but there was a significant decrease in brain/body weight ratio of the animals of all treated groups. Furthermore, there was no statistical difference between control group and all experimental groups for brain acetylcholinesterase (AChE) and blood cholinesterase (ChE) enzyme activities, although brain AChE activities were increased in rats treated with a dose of 150 and 300 mg/kg cypermethrin. Histologically, some deformation areas due to ischemia and pyknosis of the cytoplasm of the neurons were observed in brain tissues of rats treated with all doses of cypermethrin.
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  • Dong-Mei Li, Wan-Liang Lu, Xue-Qing Wang, Jian-Cheng Wang, Hua Zhang, ...
    Volume 51 (2005) Issue 3 Pages 308-316
    Released: June 01, 2005
    JOURNALS FREE ACCESS
    The objective of this study was to estimate the pharmacokinetics of the newly developed once-daily acemetacin sustained-release tablets compared with those of the commercial acemetacin sustained-release capsules. Ten male healthy Chinese volunteers were included in the study. The administration schedule was a randomized crossover design. Each volunteer received 90 mg of the tablet or the capsule in the single-dose study, and each received 90 mg of the tablet or the capsule once daily for 6 consecutive days in the multiple-dose study. The areas under the concentration-time curve (AUC0-24 hr), maximal concentrations of indomethacin (Cmax), time to reach peak concentration (Tmax), and elimination half-life (T1/2) values of indomethacin (an active metabolite of acemetacin) were 6.72 ± 0.99 μg.hr/ml, 0.82 ± 0.08 μg/ml, 4.2 ± 0.6, and 10.1 ± 4.2 hr, respectively. The steady-state AUC120-144 hr and steady-state maximal concentration of the tablets increased to 10.33 ± 1.06 μg.hr/ml and 1.14 ± 0.10 μg/ml, respectively. The pharmackinetic parameters (AUC0-24 hr, Cmax, T1/2, and mean residence time) for two formulations were not significantly different but the average Tmax of the tablets was delayed by 1 hr compared with that of the capsules (4.2 ± 0.6 vs. 3.2 ± 0.6 hr, p < 0.05). The mean relative bioavailability of the tablets was 97.9 ± 14.8% compared with that of the capsules. It could be concluded that the pharmacokinetic parameters of the newly developed sustained-release tablets are similar to those of the sustained-release capsules, excluding the Tmax value. A significant correlation was obtained between the in vivo mean absorption rate and the in vitro mean dissolution rate for the newly developed sustained tablets.
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  • Dae Kyong Kim, Yong Koo Kang, Moo Yeol Lee, Kwang-Gill Lee, Joo-Hong Y ...
    Volume 51 (2005) Issue 3 Pages 317-324
    Released: June 01, 2005
    JOURNALS FREE ACCESS
    This article was retracted. Please see the retraction notice.
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  • Tatsunori Iwamura, Yuko Ito, Nayumi Kuno, Takaharu Mizutani
    Volume 51 (2005) Issue 3 Pages 325-332
    Released: June 01, 2005
    JOURNALS FREE ACCESS
    We studied the substrate specificity of some opioid derivatives of 5,9-dimethyl-2′-hydroxybenzomorphan [1], composed of A, B, and D ring-systems of morphine, for human UDP-glucuronosyltransferase 2B7 (hUGT2B7), a typical glucuronidation enzyme to morphine and for bovine microsomal UGT. The group of nitrogen atom on the D ring (pyperidine ring) in [1] was modified with alkyl, alkenyl, alkynyl and aralkyl hydrocarbon substituents. hUGT2B7 did not react with the compounds with methyl and isopropyl groups on the nitrogen atom, but reacted with those having longer alkyl substituents of more than 3 carbon chains. Substances with alkenyl and isobutyl substituents are the best substrates (the Km value, 15 and 25 μM, respectively). Opioids with alkynyl and aralkyl hydrocarbon substituents are of low affinity (the Km value, 119 and 542 μM, respectively). Meanwhile, bovine enzyme did not react with opioid substances having methyl and isopropyl groups, like hUGT2B7. Bovine enzyme reacted well with opioid substances with alkenyl and alkynyl substituents on the same level as alkyl substituents. Thus, a clear difference between human UGT2B7 and bovine microsomal UGT was found in the reactivity of alkynyl group and this comes from species specificity. For development of effective opioid drugs, these results suggest that opioid compounds with short carbon substituents are better to maintain the effective level in the blood for a longer time, with low glucuronidation activity, as well as maintaining the analgesic potency of each drug.
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  • Yasuyuki Fujiwara, Makoto Mitani, Shuji Yasuike, Jyoji Kurita, Toshiyu ...
    Volume 51 (2005) Issue 3 Pages 333-340
    Released: June 01, 2005
    JOURNALS FREE ACCESS
    Selective cytotoxicity of chemical compounds to vascular endothelial cells is often beneficial for clinical applications including antivascular cancer therapy. In this study, the cytotoxicity of 35 organic compounds containing bismuth or antimony was evaluated based on the leakage of lactate dehydrogenase and morphologic observations in cultured bovine aortic endothelial cells and other cell types. The results indicate that only tris[2-(N,N-dimethylaminomethyl)phenyl]-bismuthane (TDPBi) had potent cytotoxicity to bovine aortic endothelial cells but not to bovine aortic smooth muscle cells and porcine kidney epithelial LLC-PK1 cells; the compound exhibited moderate cytotoxicity to human fetal lung fibroblastic IMR-90 cells. Neither inorganic bismuth nor tris[2-(N,N-dimethylaminomethyl)phenyl]stibane, in which antimony substitutes for bismuth with the same organic structure as TDPBi, exhibited cytotoxicity to vascular endothelial cells, suggesting that the entire structure of TDPBi is required for selective cytotoxicity. The present data revealed that TDPBi has selective cytotoxicity to vascular endothelial cells, which may be applicable in antivascular cancer therapy.
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RESEARCH LETTERS
  • Hirohisa Matsushita, Hiroaki Kuwabara, Satoko Ishikawa, Masataka Mochi ...
    Volume 51 (2005) Issue 3 Pages 341-345
    Released: June 01, 2005
    JOURNALS FREE ACCESS
    The antiproliferative effects of a n-butanol extract from Chlorophytum comosum (C. comosum) (spider plant) roots was tested in vitro against four human cell lines: HeLa, CCRF-HSB-2, HL-60 and U937 cells. The extract was found to have cell antiproliferative effects against HeLa, CCRF-HSB-2, HL-60 and U937 cell lines, with an IC50 value of 6.6, 5.4, 8.7 and 10.2 μg/ml, respectively. The dying cells showed characteristics of apoptosis, such as DNA fragmentation, as assessed by DNA electrophoresis analysis and the Terminal deoxynucleotidyl transferase (TdT)-mediated biotin dUTP Nick End-Labeling (TUNEL) method. These results indicate that extract from C. comosum roots can induce apoptosis in human cell lines.
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  • Hozumi Tanaka, Kumiko Nagata, Shigeto Oda, Hiroshi Edamoto, Mitsuaki K ...
    Volume 51 (2005) Issue 3 Pages 346-356
    Released: June 01, 2005
    JOURNALS FREE ACCESS
    Q10EP40, a new water-miscible and emulsified floury preparation for dietary supplements, consists of coenzyme Q10 (CoQ10), fatty acid ester of glycerin, casein, dextrin and sodium carbonate. The safety of CoQ10 bulk substance itself has been evaluated by several subacute and chronic toxicity studies in animals. However, the safety of CoQ10 preparation produced with food ingredients has not yet been fully confirmed. The present study was conducted to evaluate the toxicity of Q10EP40 in Sprague-Dawley rats with gavage administration at concentrations of 500, 1000 or 2000 mg/kg for 28 days. No deaths were observed in any group, and there were no adverse effects on general condition, behavior, body weight or food consumption, results of urinalysis, hematology, blood chemistry, ophthalmological examination, gross pathological examination or histopathological examination, or organ weights. On the basis of these findings, the no-observed-adverse effect level (NOAEL) for Q10EP40 in Sprague-Dawley rats is considered to be 2000 mg/kg/day.
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  • Teruo Tanaka, Sawa Murayama, Natuki Tuda, Masami Nishiyama, Kazuko Nak ...
    Volume 51 (2005) Issue 3 Pages 357-361
    Released: June 01, 2005
    JOURNALS FREE ACCESS
    To clarify the degradation pathway of chlorhexidine by a microbe, Pseudomonas sp. Strain No. A-3, the isolation and identification of microbial chlorhexidine degradation products were attempted. A new chlorhexidine degradation intermediate (CHDI), named CHDI-C, was isolated by extraction with ethylacetate, n-butanol, column chromatography using Silica gel, and purified by preparative thin layer chromatography. The chemical structure of this product was examined by infrared, 1H NMR, 13C NMR and fast atom bombardment mass spectra studies. Based on the spectroscopic data, this product was assumed to be a modified compound of chlorhexidine (molecular weight, MW; 530). From the proposed structure, CHDI-C was assumed to be a new chlorhexidine degradation intermediate.
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  • Miyako Mochizuki, Noboru Hasegawa
    Volume 51 (2005) Issue 3 Pages 362-364
    Released: June 01, 2005
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    We studied the ameliorative effect of (-)-epigallocatechin gallate (EGCG) on inflammatory bowel disease (IBD) induced by ethanolic 2,4,6-trinitrobenzene sulfonic acid (TNBS) in male 7-week-old rats. Intestinal lesions were associated with macroscopic damage score and measured as increase in myeloperoxidase (MPO) activity in mucosa. Pretreatment with EGCG (30 mg/kg daily i.g. for 10 days) significantly reduced macroscopic damage score, inhibited MPO activity and enhanced superoxide dismutase activity. These observations confirmed that EGCG can ameliorate acute experimental colitis by suppression of superoxide generation from colonic tissue.
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  • Yoshiki Mino, Mayumi Yukita
    Volume 51 (2005) Issue 3 Pages 365-368
    Released: June 01, 2005
    JOURNALS FREE ACCESS
    We examined the contents of different vegetables using X-ray fluorescence spectrometry and found extremely high levels of bromine (Br) [1000-16200 ppm (dry weight)] in some vegetables from an Osaka market. Examination using a bromide ion-selective electrode suggested that the bromine existed mainly as bromide ion. Since this bromine probably originated from fumigation with methyl bromide, this result suggests that fumigation methods may need to be regulated. Fifty milligrams of bromine [aceptable daily intake (ADI)/50 kg] was found in only 3.1 g (dry weight) of komatsuna (Br: 16200 ppm). These results suggest that vegetables that contain potentially harmful levels of bromide may be found in Japanese markets.
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  • Tatsuya Funahashi, Hideharu Ikeuchi, Satoshi Yamaori, Toshiyuki Kimura ...
    Volume 51 (2005) Issue 3 Pages 369-375
    Released: June 01, 2005
    JOURNALS FREE ACCESS
    The inhibitory effects of three major cannabinoids [Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), cannabinol (CBN)] contained in marijuana, an abused drug, on progesterone 17α-hydroxylase activity in rat testis microsomes were investigated. Microsomal progesterone 17α-hydroxylase activity was significantly inhibited in the presence of more than 50 μM of Δ9-THC and CBN compared with control activity, and the IC50 values for Δ9-THC and CBN were estimated to be 42.8 and 32.9 μM, respectively. CBD showed less but significant inhibitory effects on 17α-hydroxylase activity at concentrations greater than 100 μM, and the IC50 value for the cannabinoid was estimated to be 290.9 μM. Kinetic analysis using double reciprocal plots showed that the type of inhibition by CBN was competitive, whereas that of Δ9-THC and CBD was the mixed type. These results suggest that the inhibition may be due to metabolic interactions between each cannabinoid and 17α-hydroxylase.
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  • Miyuki Furusawa, Toshiyuki Tanaka, Tetsuro Ito, Asami Nishikawa, Naomi ...
    Volume 51 (2005) Issue 3 Pages 376-378
    Released: June 01, 2005
    JOURNALS FREE ACCESS
    The antioxidant activity of 28 natural and synthetic hydroxyflavonoids was estimated through the 1,1-diphenyl-2-picrylhyrazyl (DPPH) radical, superoxide scavenging activities and lipid peroxidation inhibition. The result showed the hydroxylation pattern had close relationship with the appearance of activities.
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RAPID COMMUNICATIONS
  • Noriko Tetsuchikawahara, Kyong-Son Min, Satomi Onosaka
    Volume 51 (2005) Issue 3 Pages 379-384
    Released: June 01, 2005
    JOURNALS FREE ACCESS
    Pretreatment with zinc (Zn) is known to produce tolerance to several of the toxic effects of heavy metals and pro-oxidants with or without the induction of metallothionein (MT) synthesis. We found previously that injection of high-dose Zn caused acute pancreatitis in mice. An injection of Zn (50-75 mg/kg) resulted in a significant increase in the plasma activities of exocrine enzymes, indicating acute pancreatitis, and no greater increase in Zn concentration in the pancreatic MT fraction with Zn doses. To clarify the role of MT in the pancreatic toxicity of Zn, we examined the effects of pretreatment with nontoxic doses of Zn on the induction of acute pancreatitis by Zn challenge. Pretreatment with Zn (10 mg/kg) 24 hr before Zn challenge attenuated Zn-induced acute pancreatitis. However, pretreatment with Zn only 2 hr before challenge was ineffective. Pretreatment with Zn 24 hr before resulted in more Zn in the MT fraction of pancreatic cytosol and less Zn in the low-molecular-weight fraction compared with pretreatment 2 hr before. These data indicate that pancreatic MT may diminish the toxicity of Zn by sequestering excess Zn. Moreover, Zn-induced acute pancreatitis also was attenuated by treatment with aprotinin, a trypsin inhibitor. Our findings suggest that the Zn ion — either free or bound to small molecules — is involved in the development of acute pancreatitis that includes intrapancreatic trypsinogen activation.
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  • Saori Kawamura, Daisaku Takai, Keiko Watanabe, Jun-ichi Hayashi, Kazus ...
    Volume 51 (2005) Issue 3 Pages 385-393
    Released: June 01, 2005
    JOURNALS FREE ACCESS
    Mitochondria have their own genome encoding subunits of the electron transport chain. Using cells lacking mitochondrial DNA (mtDNA, ρ0 cells), we studied the role of mtDNA in irradiation. Loss of mtDNA inhibited cell growth and reduced the level of reactive oxygen species (ROS) as compared to ρ+ cells. ρ+ cells were more resistant to irradiation than ρ0 cells. Upon irradiation, ρ0 cells showed delayed G2 arrest and decreased ability of a cell to recover from the G2 checkpoint compared to ρ+ cells. Irradiation increased the generation of ROS even more in ρ+ cells. Irradiation markedly increased the levels of phosphorylated forms of extracellular-regulated kinases, p42 and p44 (ERK1/2) in ρ+ cells, whereas phosphorylated levels of the kinases were affected slightly in ρ0 cells. Furthermore, inhibition of the ERK pathway led to a delayed G2 arrest and a delayed recovery from the arrest in irradiated ρ+ cells, and treatment with NAC also induced dysfunction of the G2 checkpoint in irradiated ρ+ cells. These results suggest that the accumulation of ROS potentiated ERK1/2 kinases after irradiation in ρ+ cells, leading to less sensitivity to irradiation. Thus, mtDNA is important for the generation of ROS that act as second messenger.
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  • Jun Shimizu, Urara Wada-Funada, Hiroshi Mano, Yoshiharu Matahira, Mits ...
    Volume 51 (2005) Issue 3 Pages 394-397
    Released: June 01, 2005
    JOURNALS FREE ACCESS
    Male BALB/c mice were administered three fucoidans with different molecular weights prepared from Okinawa mozuku (Cladosiphon okamuranus). The proportion of CD8+ cells in the spleens of mice fed with high molecular-weight fucoidan significantly increased compared with those in mice fed a control diet. In addition, the CD4+/CD8+ ratio tended to decrease and the proportion of CD11b+ cells to increase. These results suggest that high molecular-weight fucoidan promotes an increase in the proportion of murine cytotoxic T cells.
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  • Kyong-Son Min, Kayo Shida, Naoko Tanaka, Nozomu Yamashita, Noriko Tets ...
    Volume 51 (2005) Issue 3 Pages 398-404
    Released: June 01, 2005
    JOURNALS FREE ACCESS
    Cadmium (Cd) is a widespread toxic pollutant that enters humans and animals through the food chain. Cd usually is accumulated by binding to metallothionein (MT), which appears to be responsible for its detoxification in the cell. To investigate whether the Cd released from Cd-MT can cause toxicity to recur, we studied the effects of oxidative stress and contamination with multiple metals on the release of Cd from accumulated Cd-MT and recurrence of toxicity in vitro and in vivo. Incubation of Cd-MT with H2O2, ferric nitrilotriacetate (Fe-NTA) and H2O2, or Cu2+ resulted in release of Cd from its binding with MT. In vivo study, Cd was released from renal Cd-MT after mice that had accumulated Cd-MT were injected with Fe-NTA. Addition of purified Cd-MT to mouse liver cytosol did not result in inhibition of cytosolic superoxide dismutase (SOD) activity. However, treatment of Cd-MT with H2O2 or Cu2+ led to the release of Cd2+ from Cd-MT, which inhibited cytosolic SOD activity. Simultaneous injection with Cu2+ and a non-acute toxic dose of Cd significantly increased plasma aminotransferase activities, indicating hepatic injury, in mice that had accumulated Cd-MT but not in those that had accumulated Zn-MT. The hepatic concentration of Cu increased with the injected dose and the concentration of Cd in the MT fraction decreased. These results suggest that contamination with metals whose affinities for MT are higher than that of Cd may cause recurrent toxicity due to the release of Cd from accumulated Cd-MT.
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