Biomedical subjects

K S Kang

Publications and source records attributed to K S Kang.

At least 19 recordsLinked to original sources

PubMed2002

Lack of adverse effects in the F1 offspring maternally exposed to genistein at human intake dose level.

Recently there has been growing concern about endocrine disrupters (ED) derived from synthetic and natural chemicals. It has been argued that ED might cause developmental disorders in the next generations of animals and humans; however, this is still unclear. Therefore, we investigated whether maternal exposures to genistein (GEN) during gestation and lactation alter reproductive organs in the F1 offspring compared with those in 17beta-estradiol (E2)-maternally exposed F1 offspring. Pregnant Sprague-Dawley rats were treated orally with 0.4 mg/kg, 4.0 mg/kg GEN or 10 microg/kg E2. Maternal or neonatal effects on the number of live pups, implantation sites, sex ratio, anogenital distance, eyelid opening/vaginal opening and body weight of live pups were not altered by GEN or E2. The weights of reproductive organs at the adult stage F1 offspring were not altered by maternal exposure to GEN, except for the ventral prostate. However, the weight of the seminal vesicle was significantly decreased from postnatal day (PND) 21 to PND 70 in E2-treated offspring. Sperm analyses, cell count in seminiferous tubules and follicular development in the ovary were not altered by maternal exposure to GEN. Taken together, these results suggest that maternal exposure of GEN might not have adverse effects on the reproductive organs in the F1 offspring at the human intake dose level.

Animals↗

PubMed2002

Requirement of metabolic activation for estrogenic activity of Pueraria mirifica.

A wide range of chemicals derived from plant and human-made xenobiotics are reported to have hormonal activities. The present study was performed to examine the estrogenic effect of Kwao Keur, Pueraria mirifica (PM), that has been used as a rejuvenating folk medicine in Thailand, using recombinant yeast, MCF-7 cell proliferation and HepG2 cell transient transfection assay. In recombinant yeast assay, 0.025, 0.25, 2.5, 25, 2.5 x 10(2), 2.5 x 10(3), 2.5 x 10(4) ng/ml concentrations of PM did not show any estrogenic activities, while 10(-9) of 17 beta-estradiol (positive control) showed high estrogenic activity. Estrogenic activities were induced at 2.5 ng/ml to 25 microg/ml concentrations of PM in a dose-dependent manner on MCF-7 cells and the estrogenic effect of PM was blocked by tamoxifen treatment, a well-known anti-estrogen. PM also showed estrogenic effect on human hepatoma cell line, HepG2 cells, containing estrogen receptor and luciferase reporter gene. Taken together, PM in itself may have no estrogenicity in yeast system, but it has estrogenicity in MCF-7 & HepG2 cells that have human metabolic enzymes. The results indicated that PM may require metabolic activation for estrogenic activity.

Biotransformation↗

PubMed2001

Inhibition of apoptosis by pentachlorophenol in v-myc-transfected rat liver epithelial cells: relation to down-regulation of gap junctional intercellular communication.

Pentachlorophenol (PCP), a promoter of murine hepatocarcinogenesis, inhibits gap junctional intercellular communication (GJIC) in rat liver epithelial cells in vitro. To test the hypothesis that both inhibition of GJIC and apoptosis contribute to tumor promotion, we investigated the effect of PCP on both GJIC and serum deprivation-induced apoptosis in v-myc-transfected rat liver epithelial cells. The results showed that PCP inhibited apoptosis, as measured by the TUNEL assay and DNA ladder formation. Inhibition of apoptosis was associated with a decrease in GJIC. The study demonstrated that PCP has a potential for inhibiting apoptosis and GJIC, supporting the hypothesis.

Animals↗

PubMed2001

Antitumor activities of a newly synthesized shikonin derivative, 2-hyim-DMNQ-S-33.

2- or 6-(1-hydroxyiminoalkyl)-5,8-dimethoxy-1, 4-naphthoquinone(2- or 6-hyim-DMNQ) derived from the roots of Lithospermum erythrorhizon was synthesized for the evaluation of antitumor activities. Among those derivatives, 2-hyim-DMNQ-S33 was found to be a potent anticancer agent. This compound suppressed the proliferation of Radiation Induced Fibrosarcoma (RIF) cells in a dose-dependent manner. 2-hyim-DMNQ-S33 significantly prolonged the survival time by 239% as compared with Sarcoma 180 tumor-bearing control mice in vivo. We found that the compound significantly suppressed phosphorylation of extracellular signal-regulated kinase (pERK) and activated c-jun-N-terminal kinase (JNK) and protein kinase C (PKC)-alpha following 4 h-treatment. These findings indicate that 2-hyim-DMSQ-S33 exerts antitumor activities by regulating pERK, JNK and PKC-alpha.

Animals↗

PubMed2001

Preventive effect of germanium dioxide on the inhibition of gap junctional intercellular communication by TPA.

Gap junctional intercellular communication (GJIC) is thought to be essential for maintaining cellular homeostasis and growth control. In order to detect any protective agent against tumor formation, we examined the anticarcinogenic effect of a germanium dioxide (GeO(2)) using a model system of GJIC in F344 rat liver epithelial cells, named WB cells. 12-O-tetradecanoylphorbol-13-acetate (TPA), known as tumor promoters, inhibited GJIC in the epithelial cells as determined by the scrape loading/dye transfer (SL/DT) assay. And GeO(2) recovered this inhibition of GJIC. Immunostaining of connexin 43 (Cx43) protein in WB cells indicated that TPA caused a loss of Cx43 protein from the cell membranes. However, GeO(2) treatment showed re-appearance of Cx43 protein on the membrane. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blots were analyzed to determine whether the test compounds might have altered the steady-state levels of gap junction mRNA and/or connexin protein levels or phosphorylation. The inhibition of GJIC by TPA in WB cells was correlated with the hyperphosphorylation of Cx43 as measured by mobility shifts of the western blot bands of Cx43. TPA induced hyperphosphorylation of Cx43 protein, while GeO(2) appeared to partially block this hyperphosphorylation. Here, we showed that pre- and co-incubation with GeO(2) in TPA-treated WB-cells abolished down-regulation of GJIC by TPA. These data suggest that GeO(2) may inhibit tumor promotion by enhancing GJIC.

Animals↗

PubMed2001

Effects of dextromethorphan on the seizures induced by kainate and the calcium channel agonist BAY k-8644: comparison with the effects of dextrorphan.

BAY k-8644 (an L-type Ca(2+) channel agonist of the dihydropyridine class) is recognized as a potent convulsant agent. In this study, we used BAY k-8644 to explore the effects of dextromethorphan (DM) and its major metabolite, dextrorphan (DX), on the (pro)convulsant activity regulated by calcium channels. BAY k-8644 (2 mg/kg, s.c) potentiated seizures induced in rats by kainic acid (KA) (10 mg/kg, i.p.). DM appears more efficacious than DX in attenuation of KA-induced seizures. The anticonvulsant effect of a low dose (12.5 mg/kg, s.c.) of DM was reversed by BAY k-8644 (2 mg/kg) challenge. In contrast, BAY k-8644 (1 or 2 mg/kg) did not significantly affect an anticonvulsant effect from a higher dose (25 mg/kg) of either DM or DX. Intracerebroventricular injection of BAY k-8644 (37.5 microg) significantly induced seizures in mice. DM (12.5 or 25 mg/kg) pretreatment more significantly attenuated seizures evoked by BAY k-8644 than did DX (12.5 or 25 mg/kg). Furthermore, seizure activity induced by KA or BAY k-8644 was consistent with respective activator protein-1 DNA binding activity of the hippocampus. Therefore, our results suggest that the anticonvulsant effects of the morphinans involve, at least in part, the L-type calcium channel. They also suggest that DM is a more potent anticonvulsant than DX in the KA and BAY k-8644 seizure models.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed2001

Prenatal exposure to magnetic field increases dopamine levels in the striatum of offspring.

1. The putative effects of prenatal exposure to magnetic field (MF) have recently received much interest. In the present study, mice were exposed to a MF of 50 mT during gestation (0-19 days). 2. After the exposure was terminated, mothers and offspring were returned to normal laboratory conditions. We then determined changes in striatal levels of dopamine (DA) and its metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in the offspring. 3. Our results indicate that prenatal exposure to MF increases levels of DA and DOPAC in the striatum at 4, 8 and 12 weeks postnatally.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2001

Effects and neuro-toxic mechanisms of 2, 2', 4, 4', 5, 5'-hexachlorobiphenyl and endosulfan in neuronal stem cells.

Endocrine disrupters are exogenous compounds thought to mimic the action of estrogen or other hormones and influence endocrine activity in the body (Juberg, 2000). These chemicals have adverse effects not only in the reproductive system but also in the central nervous system during development and throughout life. Polychlorinated biphenyls (PCBs) are a class of environmentally persistent and widespread halogenated hydrocarbons. It has been reported that PCBs are potential neurotoxicants. Endosulfan is an organochlorine insecticide that is extensively used to control pests in vegetables, cotton, and fruits. To determine the effect of 2, 2', 4, 4', 5, 5',-hexachlorobiphenyl(2, 4, 5-HCB) and endosulfan on embryo nervous system, we isolated neural stem cells from rat brain at embryonic day 17. Isolated neural stem cells showed pluripotenty. Stem cells could differentiate into neurons and glia. Neurite formation in endosulfan and 2, 4, 5-HCB treated cells. And it appeared to be decreased as compared with that in untreated cells. In order to know the neuro-toxic mechanisms of 2, 4, 5-HCB and endosulfan in neuronal stem cells, we investigated mitogen-activated protein kinase activity (MAPK) and gap junctional intercellular communication (GJIC). Endosulfan decreased the MAPK activity in dose dependent manner. Endosulfan and 2, 4, 5-HCB inhibited GJIC compared to the untreated cell by scrape loading dye transfer (SL/DT). 2, 4, 5-HCB and endosulfan decreased the expression of connexin 43 in dose dependent manner. These results indicated that 2, 4, 5-HCB and endosulfan may inhibit differentiation and proliferation of neural stem cells and gap junctional intercellular communication which play a crucial role in the maintenance of cellular homeostasis.

Animals↗

PubMed2001

2-Bromopropane induced germ cell apoptosis during spermatogenesis in male rat.

2-Bromopropane (2-BP) causes testicular toxicity in humans and rats. However, the germ cell degeneration of testicular toxicity by 2-BP has not been understood. 2-BP at doses of 135, 405, and 1,355 mg/kg/day was daily injected subcutaneously into Sprague-Dawley rats for 28 days. At the dose of 1,355 mg/kg/day, 2-BP significantly decreased the weights of body and testes, eipididymis, seminal vesicle, and prostate, as well as daily sperm production. Atrophy of seminiferous tubules accompanied with degeneration of germ cells such as spermatogonia, spermatocytes, and elongated spermatids was observed in the testes of rats exposed to the 405 mg/kg/day and 1,355 mg/kg/day of 2-BP. TUNEL-positive germ cells were appeared in the 405 and 1,355 mg/kg/day of 2-BP-treated groups. In addition, ultrastructure alterations of apoptotic germ cells were observed by the electron microscopy study. Dead elongated spermatids were observed at 1,355 mg/kg/day after 28 days exposure. These results suggest that 2-BP impair spermatogenesis may result from apoptotic germ cell death.

Animals↗

PubMed2001

Mutagenicity of water samples from five cities in Korea.

Four doses (equivalent to 4, 2, 1, and 0.5 liter water) of organic extracts from raw, treated and drinking waters sampled from seven different treatment plants in five cities in Korea were challenged to the Ames test using S. typhimurium strains TA98 and TA100 in the presence/absence of S9 mix. The mutagenicity was usually observed from chlorine-treated (28.6%) and drinking (42.9%) waters rather than raw (3.4%) waters. The strain TA98 (33.3%) was more sensitive to detect the mutagenicity of water samples than the strain TA100 (16.7%). However, the absence of S9 mix showed higher mutagenic activity of waters compared to the presence of S9 mix, corresponding to the detection of 42.9% and 7.1%, respectively. These results indicate that the bacterial mutagenicity of treated and drinking waters may be derived from chlorination in water treatment plants but that the mutagenicity in humans may be limited due to enzymatic metabolism.

Animals↗

PubMed2001

Effects of nonylphenol, bisphenol A, and their mixture on the viviparous swordtail fish (Xiphophorus helleri).

A number of fish species have been used for studies on endocrine disrupting chemicals (EDCs). However, despite the widespread use of oviparous fish, relatively little attention has been given to viviparous species. This study investigated the effects of EDCs in a viviparous fish and examined the possible usefulness of the fish as an alternative model for the studies on EDCs. Swordtails (Xiphophorus helleri) were exposed to nonylphenol (NP), bisphenol A (BPA), and their mixture. Both short-term (3-d) and relatively long-term (60-d) exposures were carried out using adult male and 30-d-old juvenile fish, respectively. Following the short-term exposure, both NP and BPA caused vitellogenin mRNA expression. Flow cytometric analysis and terminal deoxynucleotidyl transferase assay on the testes of treated fish indicated reproductive damage. Histopathological analysis found degenerative and necrotic cells in seminiferous tubules following the exposure to 100 ppb NP. The testes with lesions were also associated with highly suppressed spermatogenesis. Following the long-term exposure, both NP and BPA exposures significantly affected the growth of swordtails. In all cases, the results showed that the mixture was always more potent than a single chemical and that swordtail fish can be a useful model for the study of endocrine disruptors.

Air Pollutants, Occupational↗

PubMed2000

Immature uterotrophic assay is more sensitive than ovariectomized uterotrophic assay for the detection of estrogenicity of p-nonylphenol in Sprague-Dawley rats.

Many efforts have been made to develop assays for detecting endocrine disrupters (EDs). Among them, uterotrophic assay has been known efficient for detecting EDs, especially estrogenic compounds. This study was performed to compare the immature uterotrophic assay with an ovariectomized assay using p-nonylphenol (NP), a weakly estrogenic compound. NP was given to either immature or ovariectomized rats subcutaneously or orally (only immature) at doses of 10, 100, and 1000 mg/kg for 3 days. After treatment with NP, the rats were examined for parameters such as uterine weight, uterine weight per body weight ratio, luminal epithelial height of uterus and vagina, diameter of uterine ducts, and number of uterine glands. Both systems were shown to increase uterine weight in a dose-dependent manner. In the immature system (subcutaneous injection), uterine weight, diameter of uterine duct and vaginal luminal epithelial height were significantly increased at 100 mg/kg/day, while in the ovariectomized system these parameters were not significant at the same dose (except for vaginal luminal epithelial height). These results suggest that the immature system (subcutaneous injection) might be most sensitive to detecting a weakly estrogenic compound and that the measurement of vaginal epithelium is a good end-point.

Animals↗

PubMed2000

Formation of fibrillar multimers of oat beta-glucosidase isoenzymes is mediated by the As-Glu1 monomer.

Oat beta-glucosidase (EC 3.2.1.21) exists in two isomeric forms of homomultimer (type I) and heteromultimer (type II), which are comprised of two 60 kDa monomers of As-Glu1 and As-Glu2. The cDNA of As-Glu2 was cloned in this study, whereas As-Glu1 was previously cloned as As-P60. The As-Glu2 cDNA encodes a plastid-directing transit peptide of 57 amino acid residues and a mature protein of 521 amino acid residues. The amino acid sequence of As-Glu2 is highly homologous to that of As-Glu1, except for their C-terminal portions. When the two cDNAs of the mature proteins were expressed as T7.Tag-fused proteins in Escherichia coli, they produced soluble and enzymatically active T7.Tag-As-Glu1 and T7.Tag-As-Glu2 proteins. The T7.Tag-As-Glu1 was assembled into a donut-shaped hexamer ring which was in turn stacked in integer numbers to form long fibrillar homomultimers of different lengths with a molecular mass of up to several million daltons. On the other hand, the T7.Tag-As-Glu2 primarily formed a dimer rather than a multimer. When both cDNAs of As-Glu1 and As-Glu2 were co-expressed as T7.Tag-fused mature proteins, they were also assembled into a hexamer ring comprised of the two monomers in a 1:1 stoichiometry. The heteromeric hexamer was stacked in smaller numbers to form the heteromultimer of T7. Tag-As-Glu1 and -As-Glu2. The results indicate that the As-Glu1 monomer plays a crucial role in the formation of both the As-Glu1 homomultimer and the As-Glu1 and As-Glu2 heteromultimer. We describe here a unique structure for the oat beta-glucosidase fibrillar multimer that is formed by stacking the hexamer rings composed of As-Glu1 and/or As-Glu2.

Amino Acid Sequence↗

PubMed2000

Restoration of gap junctional intercellular communication by caffeic acid phenethyl ester (CAPE) in a ras-transformed rat liver epithelial cell line.

Caffeic acid phenethyl ester (CAPE), an active ingredient of honeybee propolis, has been identified as having anti-inflammatory, anti-viral and anti-cancer properties. Since the deficiency of gap junctional intercellular communication (GJIC) has been shown to be a characteristic of most cancer cells, this study was designed to test the hypothesis that the anti-carcinogenic activity of CAPE might be related to its ability to restore GJIC in tumorigenic GJIC-deficient cells (WB-ras2 cells). The results showed that CAPE restored GJIC, phosphorylation of connexin 43 (Cx43) and its normal localization on the plasma membrane in WB-ras2 cells after 3 days at 5 microg/ml concentration. Additionally, CAPE inhibited growth in soft agar and decreased the protein level of p21(ras). The results are consistent with the hypothesis that the anti-cancer mechanism of CAPE may be mediated by its ability to restore GJIC.

Animals↗

PubMed2000

Preventive effect of epicatechin and ginsenoside Rb(2) on the inhibition of gap junctional intercellular communication by TPA and H(2)O(2).

The anticarcinogenic effects of epicatechin (EC) and ginsenoside Rb(2) (Rb(2)), which are major components of green tea and Korea ginseng, respectively, were investigated using a model system of gap junctional intercellular communication (GJIC) in WB-F344 rat liver epithelial cells. 12-O-tetradecanoylphorbol-13-acetate (TPA) and hydrogen peroxide, known as cancer promoters, inhibited GJIC in the epithelial cells as determined by the scrape loading/dye transfer assay, fluorescence redistribution assay after photobleaching, and immunofluorescent staining of connexin 43 using a laser confocal microscope. The inhibition of GJIC by TPA and H(2)O(2) was prevented with treatment of Rb(2) or EC. The effect of EC on GJIC was stronger in TPA-treated cells than in H(2)O(2)-treated cells, while the effect of Rb(2) was opposite to that of EC. EC, at the concentration of 27.8 microg/ml, prevented the TPA-induced GJIC inhibition by about 60%. Rb(2,) at the concentration of 277 microg/ml, recovered the H(2)O(2)-induced GJIC inhibition by about 60%. These results suggest that Rb(2) and EC may prevent human cancers by preventing the down-regulation of GJIC during the cancer promotion phase and that the anticancer effect of green tea and Korea ginseng may come from the major respective components, EC and Rb(2).

Animals↗

PubMed2000

Genotoxicity of drinking water from three Korean cities.

Organic content of drinking tap water from Seoul, Taejon, and Suwon was extracted with an XAD-2 resin column and organic solvents. Four doses of the extract equivalent to 4, 2, 1, and 0.5 l water were tested for mutagenicity in Salmonella typhimurium strains TA98 and TA100 in the presence and absence of S9 mix. The organic extracts of the water from all three cities were mutagenic in TA 98 without S9 mix and in TA 100 with and without S9 mix. The highest number of revertants per plate was found in the absence of S9 mix. Three doses of the extract (equivalent to 22, 11, and 3.7 l water) were also tested in the bone marrow micronucleus test using BDF1 mice. At the highest dose, a significant increase of the micronucleus frequency was observed. The time required to be on the effect, however, varied with the source of the water. Our results indicate that the drinking tap waters from the three cities were genotoxic clearly in the bacterial test and also in the in vivo assay with mice. As we found no genotoxicity of the source water as seen in a previous study, it is likely that the chlorination process leads to the genotoxicity of the tap water.

Animals↗

PubMed2000

Effects of dizocilpine pretreatment on parvalbumin immunoreactivity and Fos expression after cerebral ischemia in the hippocampus of the Mongolian gerbil.

The mechanisms of ischemic neuronal death have been focused on glutamate receptor activation and subsequent elevation of intracellular Ca2+ concentration. The purpose of this study was to evaluate the effects of dizocilpine, an NMDA receptor antagonist, pretreatment on Fos expression and parvalbumin (PV, calcium binding protein) immunoreactivity in the hippocampus of the mongolian gerbil after global ischemic insults. The number of PV-immunoreactive (PV-ir) neurons in CA1 were significantly decreased from 1 day after cerebral ischemia, while dizocilpine pretreatment completely suppressed the loss of PV-ir neurons in CA1. Dizocilpine pretreatment also protected the structural loss of microtubule-associated protein 2 immunoreactivity in CA1 after ischemic insults. In addition, dizocilpine pretreatment increased Fos expression in both hippocampal CA3 and CA4 after 3 hr ischemic reperfusion as compared to that of the saline pretreated group. Subsequently, the Fos-defined cellular activity of PV-ir neurons was slightly increased by dizocilpine pretreatment in the hippocampal area. This study demonstrated that NMDA receptor mediated calcium influx was associated with the loss of PV-ir neurons in CA1 hippocampal region, and that dizocilpine pretreatment increased Fos expression and the neuronal activity of PV-ir neurons in the non-vulnerable region of hippocampus after cerebral ischemia. Based on this data, we conclude that the protective effect of dizocilpine may be induced by the regulation of calcium overload, or by the upregulation of a neuroregenerative initiator such as Fos protein.

Animals↗

PubMed2000

Surgical treatment of intractable epilepsy accompanying cortical dysplasia.

OBJECT: Surgical treatment of cortical dysplasia (CD) together with intractable seizures is challenging because both visualization and localization of the lesion are difficult, correlation with seizure foci requires comprehensive study, and the surgical outcomes reported thus far are unsatisfactory. The authors report their experience in the surgical treatment of CD classified according to a surgical point of view. METHODS: The definition of CD used in this study was a dysplastic lesion visible on magnetic resonance (MR) images or a lesion that, although not visible on MR images, was diagnosed as moderate-to-severe dysplasia by using pathological analysis. During the last 4.5 years, the authors treated 36 patients with intractable epilepsy accompanied by CD. They divided the 36 cases of CD into four characteristic groups: Group A, diffuse bilateral hemispheric dysplasia; Group B, diffuse lobar dysplasia; Group C, focal dysplasia; and Group D, a moderate to severe degree of CD with a normal appearance on MR images. All but one patient in Group C were monitored in the epilepsy monitoring unit by using subdural electrodes for seizure localization and functional mapping. The incidence of CD among a cohort of 291 patients who had undergone epilepsy surgery at the authors' center during the study period was 12.4%. The mean age of the 36 patients was 21.3 years and the mean age at seizure onset was 8.5 years. The mean follow-up period was 26 months. Twenty-six patients (72.2%) belonged to Engel Class I or II (20 and six, respectively). There were five cases in Group A, nine in Group B, nine in Group C, and 13 in Group D. Patients in Groups A and B were significantly younger at seizure onset and had significantly poorer surgical outcomes compared with patients in Groups C and D (p < 0.05). If outcome is compared on the basis of the extent of removal of CD, patients in whom CD was completely removed had significantly better outcomes than those in whom CD was only partially removed (p < 0.001). CONCLUSIONS: The authors conclude that intractable epilepsy accompanied by CD can be treated surgically using comprehensive preoperative approaches. Deliberate resective procedures aimed at complete removal of dysplastic tissue ensure excellent seizure control without permanent neurological deficit.

Adolescent↗