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REFERENCE LINKING PLATFORM OF KOREA S&T JOURNALS
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Journal DOI :
The Korean Society of Toxicology
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Volume & Issues
Volume 17, Issue 4 - Dec 2001
Volume 17, Issue 3 - Oct 2001
Volume 17 - Jul 2001
Volume 17, Issue 2 - Jun 2001
Volume 17, Issue 1 - Mar 2001
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Seizure-related Encephalopathy in Rats Intoxicated with Diisopropylfluorophosphate
Kim, Yun-Bae ; Hur, Gyeung-Haeng ;
Toxicological Research, volume 17, issue 2, 2001, Pages 73~82
The incidence and distribution of necrotic and apoptotic neural cells, and activated astrocytes in the brain of rats intoxicated intra peritoneally with diisopropylfluorophosphate were investigated. Pyridostigmine bromide (0.1 mg/kg) and atropine methylnitrate (20 mg/kg) were pretreated intramuscularly 30 min and 10 min, respectively, prior to diisopropylfluorophosphate (4-10 mg/kg) administration. Diisopropylfluorophosphate induced severe limbic seizures, early necrotic and delayed apoptotic brain injuries, and rapid astrocytic responses. The necrosis, which was closely related to seizure intensity, was observed as early as 1 hr after intoxication predominently in hippocampal pyramidal cells, cerebellar Purkinje cells and neurons in pyriform/entorhinal cortices, showing malacia of neurophils. In contrast, apoptosis started to appear 12 hr after intoxication in neurons in thalamus, amygdala and neocortex, and ephendymal cells surrounding the 4th ventricle. Since marked apoptosis was induced in rats exhibiting relatively-low seizure intensity, the degree of necrosis and apoptosis was shifted to each type of injury according to the seizure intensity. Activated astrocytes, observed within 1 hr along the limbic system, were suggested to affect the neural injury patterns by producing high level of nitric oxide. However, the distribution of activated astrocytes was not in parallel with those of necrotic or apoptotic injuries, implying that the astrocytic responses resulted from seizure activity rather than neural injuries. Furthermore, astrocytes in malacic tissues disappeared during the severe limbic seizures. Therefore, it would be one of the cautionary notes on the expression of glial fibrillary acidic protein in astrocytes as a biochemical marker of brain injuries following acute exposure to organophosphates.
Historical Control Data for Developmental Toxicity Study in Sprague-Dawley Rats
Toxicological Research, volume 17, issue 2, 2001, Pages 83~90
The background control data were compiled from rat developmental toxicity studies con-ducted at Toxicology Research Center, KRICT during the 1993-1999 period. These data were assembled in order to provide background in formation for the maternal and fetal data collected in 13 developmental toxicity studies using Sprague-Dawley rats. A total of 325 mated females were used in these studies during the seven-year period and overall pregnancy rate of these females was 93.8%. The present background control data included body weights, food consumption, hematological values, and organ weights of pregnant females, caesarean section data, and fetal examination data. These data can be used not only as a historical database for the meaningful interpretation of data from reproductive and developmental toxicity studies, but also as a contribution to biological characterization oj Sprague-Dawley rats.
Dermal and Ocular Irritation Studies of Some Phthalates in Rabbits
Toxicological Research, volume 17, issue 2, 2001, Pages 91~96
Phthalates are widely used as plasticizers to impart softness and flexibility to normally rigid polyvinylchloride products. However, there are not much studies jar dermal and ocular irritation toxicity of phthalates. So we investigated the skin or eye irritation effect of some phthalates which was not reported. The primary skin irritation of diethyl phthalate (DEP), diisodecyl phthalate (DIDP), diisononyl phthalate (DINP), dipropyl phthalate (DPP) and dipropyl phthalate (DPrP) was studied. The ocular irritation of dibutyl phthalate(DBP), DIDP, DINP, DPP and DPrP was also studied. DEP, DIDP, DINP, DPP, and DPrP were found to be non-irritating to the skin of the test animals. DBP, DIDP, DINP and DPP were found to be non-irritating to the eye of the rabbits. DPrP caused the slight irritations to the eye in 1 or 2 days after treatment but irritation of the animals was soon recovered.
Effects of Gamma-Irradiated Korean Ginseng on Fertility and General Reproductive Toxicity in Rats
Toxicological Research, volume 17, issue 2, 2001, Pages 97~106
Korean ginseng products have been fumigated with ethylene oxide (EO) for sterilization and prolongation of storage periods. However, there had been controversies indicating that the consumption of food treated with EO might cause harmful effects in human. Since, in Korea the use of EO gas for food treatment was banned in 1991. Since then, irradiation technique has been developed as an alternative. This study was carried out to investigate the effects of irradiated ginseng on fertility, and reproductive and developmental toxicity. Either EO gas fumigated or gamma-irradiated ginseng was administered to male rats by oral gavage for 63 days during the premating period. Female rats were administered from 14 days before mating to day 20 of gestation or to day 21 of lactation. The exposure amount of irradiation used was 5, 10 and 30 kGy, respectively. There were no treatment related changes of darns in clinical signs, and parturition. No treatment related changes in food consumption, body/organ weights, male/female reproductive and fertility performances were observed. F1 fetuses showed no external abnormality. Reflex/sensory junctions, physical/behavioral development, and reproductive performance of F1 rats were not adversary affected. The results of this study show that gamma-irradiated ginseng, up to 30 kGy, has no adverse effects on the fertility, reproduction and development in Wistar rats.
Four-week Repeated Oral Dose Toxicity Study of A New Hepatotherapeutic Agent GODEX (HEPADIF-S) in Rats
Toxicological Research, volume 17, issue 2, 2001, Pages 107~114
This study was designed to evaluate a repeated oral dose toxicity of a new hepatotherapeutic agent GODEX in Sprague-Dawley rats. Male and female rats were orally administered with dosages of 500, 100, 20, and 0 /kg/day of GODEX daily for 4 weeks, respectively. There were no dose-related changes in clinical signs, body weight changes, food and water consumption, opthalmoscopy, organ weights, urine analysis, biochemical examination, and hematological findings of all animals treated with GODEX. Gross and histopathological findings revealed no evidence of specific toxicity related to GODEX. These indicate that GODEX may have no side effects and its oral maximum tolerated dose value may be over 500 mg/kg in rats.
Effects of Di(n-butyl) Phthalate on the Developing Immune System of Fetal and Neonatal SD Rats
Toxicological Research, volume 17, issue 2, 2001, Pages 115~121
Some of endocrine disruptors with sexual hormone-like effects have been increasingly reported to be immunotoxic in many species in recent several years. Phthalate esters have possible effects on the endocrine system. Prenatal exposure to di(n-butyl) phthalate (DBP) has been reported to impair the androgen-dependent development of the male reproductive tract in rat. Therefore, the immunomodulatory effect of DBP was investigated in the developing immune system of fetal and neonatal Sprague-Dawley rats. Timed-bred pregnant SD rats were given to the doses of 0, 250, 500, and 750 mg DBP/kg
body weight /day by gavage once a day from gestational day (GD) 5 to 18. On GD19 or GD22/postnatal day one (PD1), the dams were euthanized, and the changes in organ weights and thymus phenotypes were examined for their offsprings. At 750 mg DBP/kg
b.w./day in maternal exposure group, GD19 fetuses showed decreases in body weight. The spleen/body weight ratios were reduced in GD 19 fetuses from the dams exposed to 500 and 750 mg DBP/kg
b.w./day. There were no significant changes in thymus and spleen cellularities though these cellularities showed a tendency to decrease in a dose dependent way. In the DBP-exsposed GD22/PD1 offsprings, the body weights, the relative organ weights and the cellularities did not exhibit alteration. Additionally, the percentages of CD3
, and CD4
) and CD3
, and CD4
) thymocyte subsets were not changed in any DBP-treated group. The proliferative responses of splenic T cells to Con A and B cells to LPS were decreased in all DBP-exposed GD22/PD1 offsprings.
The Cytotoxic Effects of Paraquat and Bentazon Compensatory Effects of 3-Methylcholanthrene on Kindney of the Rat
Toxicological Research, volume 17, issue 2, 2001, Pages 123~129
This study were carried out to investigate cytotoxicity of paraquat and bentazon that is scattering to farm products were essensial for human diet and compensatory effects of 3-methylcholanthrene (3-MC) in vitro and in vivo. In vitro, The 5.0
cell/ml of NIH 3T3 fibroblast in each well of 24 multidish were cultured. After 24 hours, the cells were treated with solution of paraquat and bentazon (1, 25, 50, 100 pM respectively). After the NIH 3T3 fibroblast of all groups were cultured in same condition for 48 hours, Sulfohordamin B Protein (SRB) assay were performed to evaluate the cytotoxicity of cell organelles. Paraquat and bentazon
M respectively. In vivo, Sprague Dawley male rats divided into paraquat and bentazon only administered group and simultaneous application group of paraquat and bentazon and 3-MC. At 30 min. and 1, 3, 6, 12, 24, 48 and 96 hrs. interval after each treatment, the animals were sacrificed by decapitation and kidney were immediately removed, immersed in fixatives, and processed with routine method for light microscopic study. Paraffin sections were stained with H-E, PAM, and PAS. Under the light microscope, atrophic change of renal corpuscles were frequently observed from 3 hrs after paraquat and bentazon treatment. The increase of the mesangium was apparent from 12 hrs later after paraquat and bentazon treatment. Necrotic changes of the epithelium and loss of brush border of proximal tubules were most severe at 48 hrs after paraquat and bentazon treatment, respectively. In contrast there were no evidences of the toxic effects on renal tissues at 48hrs in paraquat and bentazon plus 3-MC treated groups.
Induction of Apoptosis by Baicalein in Human Leukemia HL-60 Cells
Kim, Jang-Ho ; Park, Sun-Young ; Shin, Kwang-Sig ; Yoo, Byung-Sun ;
Toxicological Research, volume 17, issue 2, 2001, Pages 131~137
Baicalein, a major flavonoid of extract from Scutellaria baicalensis Georgi, has been shown to exhibit antioxidant and anti proliferative effects. In the present study, we investigate the effects of baicalein on viability and induction of apoptosis in human promyelocytic leukemia HL-60 cells. Baicalein was found to induce apoptosis of HL-60 cells in a concentration-dependent and time-dependent manner. When HL-60 cells were exposed to 100
baicalein for 6h, the viability was decreased remarkably to 27% of control, whereas DNA fragmentation was significantly increased to 64%. Nucleosomal fragmentation of baicalein treated HL-60 cells, a hallmark of apoptosis, was further identified by agarose gel electrophoresis (DNA ladder). Flow cytometric analysis showed that apoptotic cells were increased to 66.6% after treatment with 100
baicalein for 6 h. Baicalein-induced apoptosis of HL-60 cells was reduced by 1h pretreatment with inhibitor of caspases, z-Asp-
-DCB. At 3 and 10
-DCB, DNA fragmentation of HL-60 cells induced by baicalein (50
) was 36.8 and 17.1 %, respectively, whereas, that of HL-60 cells treated by baicalein (50
) without pretreatment with inhibitor of caspases was 62.7%. These data suggest that baicalein induces apoptosis in human leukemia HL-60 cells, and that caspase enzymes might be involved in baicalein-induced apoptosis.
Effect of 17
-Estradiol on Sexual Behavior and Reproductivity of Male Medaka (Oryzias latipes)
Toxicological Research, volume 17, issue 2, 2001, Pages 139~142
Sexual behavior and reproductivity of male fIsh were studied as an in vivo screening method of endocrine disruptors. Male medaka (Oryzias latipes) were exposed to 17
-estradiol at nominal concentrations of 2 and 20
/l for 14 days. After exposure of the chemical, sexual behavior between male medaka and normal female which were injected with prostaglandin
just before the test, was analysed by using video camera for one hour. Normal control male showed courtship dancing such as following, guarding, dancing and crossing while 17
-estradiol treated male did not show any type oj courtship dancing. Furthermore, fecundity and fertility were significantly decreased in the treated group. It was suggested that analysis of sexual behavior could be a useful endpoint for the screening of the endocrine disruptors.
Comparison of Eye Irritation Potency with Skin Irritation and Cytotoxicity Potency of Anti-wrinkle Agents
Toxicological Research, volume 17, issue 2, 2001, Pages 143~149
In the present study, we examined eye irritation oj six anti-wrinkle agents (ascorbic acid, glycolic acid, all trans-retinoic acid, ginseng extract, retinol, EB). We also compared eye irritation with skin irritation and cytotoxicity in HaCaT cells by these agents. The highest eye irritation was found in glycolic acid, but all trans-retinoic acid showed the highest skin irritation. The rank of eye irritation was not correlated with the cytotoxicity of agents. This result shows that eye irritation potency by these agents were not correlated with skin irritation potency, and cytotoxicity in HaCaT cells.
Therapeutic Effect of HM 10411 on Neutropenia Caused by Anticancer Agents in Mice
Toxicological Research, volume 17, issue 2, 2001, Pages 151~157
Neutropenia is a major dose-limiting side effect of cancer chemotherapy. The therapeutic effect of HM 10411 was examined on neutropenia caused by anticancer agents. Neutropenia in normal ICR mice was induced by a single combined intraperitoneal injection of 130 mg/kg of cyclophosphamide (CPA). 4.5 mg/kg of doxorubicin (DXR). and 1 mg/kg of vincristine (VCR) on day O. Neutropenia in tumor-bearing mice was made by a single intraperitoneal injection of 200 mg/kg of cyclophosphamide (CPA) into BALB/c mice bearing Colon 26 adenocarcinoma at 7 day after tumor implantation. HM 10411 or filgrastim (100
/kg/day) was subcutaneously administered for 5 consecutive days starting 1 day after injection of anticancer agents in order to stimulate neutrophil production. Injection of HM 10411 accelerated the recovery from these anticancer drug-induced neutropenia. In normal and tumor-bearing mice. neutrophil production efficacy of HM 10411 was similar than that of filgrastim. These results suggest that HM 10411 could be useful in the clinical treatment for neutropenia induced by anticancer agents.
Anti-emetic Effect of Ondaron in Ferrets
Toxicological Research, volume 17, issue 2, 2001, Pages 159~161
The anti-emetic effect of a 5-HT
receptor antagonist, Ondaron, was compared with that of the approved ondansetron agent, Zofran
in the ferrets. Emesis was induced by single intraperitoneal injection of cisplatin 10 mg/kg, and Ondaron or Zofran
was injected intraperitoneally in a dose of 1.0 mg/kg, respectively. Ondaron and Zofran
effectively antagonised the emetic response for 4 hours after injection. They significantly reduced the number of vomiting and retching, and prolonged the latency to the first episode. The anti-emetic effect of Ondaron was almost the equal to that of Zofran
. These results suggest that Ondaron is an effective anti-emetic agent against cisplatin-induced emesis, and its anti-emetic potency is similar to that of 5-
receptor abtagonist, Zofran