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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 13, Issue 4 - Dec 1997
Volume 13, Issue 3 - Sep 1997
Volume 13, Issue 1_2 - Jun 1997
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Acute Toxicity of Pectenotoxin 2 and Its Effects on Hepatic Metabolizing Enzyme System in Mice
Toxicological Research, volume 13, issue 3, 1997, Pages 183~186
Acute toxicity of pectenotoxin 2 (PTX2) was examined in mice. Treatment of mice with a toxic dose of PTX2 resulted in clinical signs such as ataxia, cyanosis and an abrupt decrease in body temperature. Histopathological studies revealed that the liver is the major target organ for PTX2. Activities of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and sorbitol dehydrogenase (SDH) were significantly elevated by PTX2 administration. Glucose-6-phosphatase activities were not changed by the treatment. The PTX2 treatment decreased relative liver weight without changing the body weight. The effect of PTX2 on hepatic drug metabolizing enzyme system was determined. An ip dose of PTX2 (200 $\mu$g/kg) induced a significant decrease in the hepatic microsomal protein content. Cytochrome P-450 content, cytochrome b$_5$ content, NADPH cytochrome c reductase, aminopyrine N-demethylase activities, or hepatic glutathione content were not altered by PTX2 treatment.
Apoptotic Cell Death of Mouse Splenocytes by Polychlorinated Biphenyls and Its Prevention by Serum
Yoo, Byung-Sun ; Kim, Hwan-Mook ;
Toxicological Research, volume 13, issue 3, 1997, Pages 187~191
Cell death induced by polychlorinated biphenyls (PCBs), environmental toxicant, was investigated in mouse splenocytes. The fragmentation of intact DNA, a parameter of apoptotic cell death, was evaluated qualitatively by agarose gel electrophoresis analysis and quantitatively by diphenylamine reaction method. PCBs induced apoptotic cell death of splenocytes in a dose- and time- dependent manner. The effect of serum on the apoptotic cell death induced by PCBs was also investigated. The DNA fragmentation induced by PCB treatment in serum-free medium was clearly inhibited by an addition of serum to the culture medium. The decrease of DNA fragmentation due to serum addition was accompanied with the increase of cell viability.
Application of Iranian Medicinal Plants to the Treatment of Liver Injury.
Kalantari, H. ; Arzi, A. ; Haghperast, M. ; Chang, Il-Moo ;
Toxicological Research, volume 13, issue 3, 1997, Pages 193~196
Matricaria Chammomillal L., Foemiculum Vulgare mill, and Plantago Psylium L. have been screened for their hepato protective activities against liver damge induced by
intoxication in mice. Hydroalcoholic extractions (2:8) of herbal drugs were concentrated in vacuo and concentrated crude extracts of Matrica Chammomilla L. and Foeniculum Vulgare mill were orally administered at doses of 100 mg/kg, 200 mg/kg, 400 mg/kg, and 800 mg/kg. Plantago Psyllium was given at doses of 50 mg/kg, 100 mg/kg, 200 mg/kg, and 400 mg/kg. Liver protective activities of these herbs were determined after administration of
Liver size, serum enzyme activities, sleeping time, and histopatology of the liver were examined one hour after administration of
. ALT and AST activities, liver weight and sleeping time decreased in groups that received 400 mg/kg of Matricaria Chammomilla L. or Foeniculum Vulgare. Histological investigation showed significant increase in hepatic cell regeneration and reduction in liver injury. The group that received 100 mg/kg Plantago Psylium showed liver protection but protection was not significant in other doses.
Mutagenicity and Hepato-Toxicity of Kyoaesamultang
Toxicological Research, volume 13, issue 3, 1997, Pages 197~202
Kyoaesamultang(KAT) has been used as an important prescription for various diseases including threatened abortion, associated with pregnancy in traditional medicine. In oder to identify the safety of KAT, this study was designed to determine mutagenicity and hepato-toxicity. In Rec-assay, Bacillus subtills H-17(
) and M-45(
) strains were used to clarify the DNA damage property. In Ames test, Salmonella typhimurium TA98 and TA100 were used for mutagenicity testing. In SOS umu test, Salmonella typhimurium TA1535 containing plasmid pSK1002 was used as a tester strain, and the levels of umu operon expression were monitored by measuring the
-galactosidase activity. From tested results, KAT did not show DNA damage and mutagenicity. On the other hand, hepato-toxicity of KAT to female ICR mice was monitored by the measurements of s-GOT, s-GPT and LDH activities after oral feeding for 15days. KAT showed 34% increase of s-GOT and s-GPT activities, also exhibited 35% increase of LDH activity in mice sera.
Antigenicity Studies of M3S Tumor Necrosis Factor-$\alpha$(M3S TNF), a TNF Mutein
Toxicological Research, volume 13, issue 3, 1997, Pages 203~208
The antigenic potential of M3S tumor necrosis factor-
(M3S TNF), which is a mutated form of TNF(TNF mutein) designed to reduce adverse effects of wild type human TNF, was investigated in the present study. The antigenicity of M3S TNF was examined by conducting active systemic anaphylaxis (ASA) test in guinea pigs, heterologous(mouse-rat) passive cutaneous anaphylaxis(PCA) test and passive hemagglutination(PHA) test. The experimental animals were divided into low, medium, high and the highest dose groups and the groups with or without immunoadjuvant, sensitized according to the appropriate schedule and challenged. In ASA test, when challenged with 120
/animal, moderate to severe positive anaphylactic responses were observed in groups sensitized with 12
/animal and 120
/animal+Freund's complete adjuvant. In PCA test, positive responses were observed in the group sensitized with the highest dose emulsified with an alum(12
/animal+alum). In PHA test, positive responses were observed in the group sensitized with 3
/animal emulsified with an alum. All the other groups in each experiment showed negative responses. Based on these results, M3S TNF is considered to have some antigenic potential.
Residue of Clindamycin in the Muscles of Eel and Flounder Infected by Streptococcus sp. by HPLC
Jang, Won-Cheoul ; Shim, Sang-Kyun ; Heo, Gang-Joon ;
Toxicological Research, volume 13, issue 3, 1997, Pages 209~213
Residue and recoveries of clindamycin were investigated by reversed-phase high performance liquid chromatography (RP-HPLC) which was infected for the control of streptcoccal infection in Anguilla japonica and Paralichthys olivaceusis. Detection limit was 0.1 ppm. Recoveries of clindamycin in muscles of flounder and eel were 80.4 and 78.8%, respectively. The clindamycin in eel and flounder was detected up to 13 and 15 days after dosing, respectively.
Seizure-related Brain Injuries in Organophosphate Poisoning
Hur, Gyeung-Haeng ; Lee,Yong-Soon ; Han, Byung-Gon ; Yeon, Gyu-Baek ; Kim, Yun-Bae ;
Toxicological Research, volume 13, issue 3, 1997, Pages 215~222
The features of seizure-related brain injuries in rats poisoned i.p. with diisopropylfiuorophosphate were investigated. Pyridostigmine bromide (0.1 mg/kg) and atropine methylnitrate (20 mg/kg), which are centrally inactive, were pretreated i.m. 30 min and 10 min, respectively. before diisopropylfluorophosphate (10 mg /kg,
) poisoning to reduce the mortality and eliminate peripheral signs. Diisopropylfluorophosphate induced severe limbic seizures, and early necrotic and delayed apoptotic brain injuries. The necrotic brain injury, which was closely related to seizure intensity, was exerted as early as 1 hr predominently in hippocampus and piriform cortex. showing spongiform change (malacia) of neurophils in severe cases, in contrast to a typical apoptotic (TUNEL-positive)pattern after 12 hr in thalamus, and a mixed type in amygdala. Nitric oxide content in cerebrospinal fiuid significantly increased after 2 hr, reaching a maximal level at 6 hr. Pretreatment with
-nitroarginine, an inhibitor of nitric oxide synthase, reduced nitric oxide content and attenuated only apoptotic brain injury in all four brain regions examined without affecting seizure intensity and necrotic injury. Taken together, early necrotic and delayed apoptotic brain injuries induced by diisopropylfiuorophosphate poisoning in rats may be related to seizure intensity and nitric oxide production, respectively.
Generation of Reactive Oxygen Species by Nonenzymatic Reaction of Menadione with Protein Thiols in Plasma
Toxicological Research, volume 13, issue 3, 1997, Pages 223~228
Quinones have been reported to undergo nonenzymatic reaction with thiols to generate reactive oxygens. It is therefore possible that the nonenzymatic reaction of quinones with thiols in plasma could lead to potentJared cellular toxicity or disease. When 1 mM menadione was added in plasma under pH 11.2, 7.4 and 5.0, the increase in oxygen consumption rate was the order of pH 11.2 > pH 7.4 > pH 5.0. In addition, oxygen consumption rates under plasma anticoagulated with trisodium citrate solution (pH 7.85) was significantly higher than those with acid-citrate-dextrose solution (pH 6.87). SOD and catalase reduced the rate of oxygen consumption induced by menadione in plasma. Taken together, these results suggest that the menadione-induced increased oxygen consumption was due to nonenzymatic reaction of menadione with thiols in the plasma. The presence of plasma has an additive effect on the increased oxygen consumption rates induced by the menadione treatments on our model tissue, platelets, as compared between washed platelet (WP) and platelet rich plasma (PRP). Cytotoxicity, as determined by LDH release, are well correlated with the oxygen consumption rates observed in each system and strongly suggest that menadione-induced cytotoxicity can be increased with the presence of blood plasma.
Chemical-Induced Cytotoxicity in Platelet Rich Plasma Isolated from Rats
Seung, Sang-Ae ; Chung, Seung-Min ; Lee, Sun-Koo ; Lee, Joo-Young ; Kim, Jeong-Sun ; Chung, Jin-Ho ;
Toxicological Research, volume 13, issue 3, 1997, Pages 229~235
The elevation of intracellular calcium in various tissues due to oxidative stress induced by either menadione or adriamycin has been well documented. The increase of calcium level in platelets results in aggregation of platelets. To test the hypothesis that chemically induced calcium elevations can play a role in platelet aggregation, we have studied the effects of menadione and adriamycin on aggregation of platelets isolated from female rats. Treatment with menadione and adriamycin to platelet rich plasma (PRP) appeared to induce platelet aggregations up to 60%, as determined by aggregometry. However, exposure of PRP to rnenadione or adriamycin led to a loss of viability, as measured by lactate dehydrogenase (LDH) leakage. Morphological studies of platelets revealed that, when PRP was treated with menadione, aggregates of platelets were not observed and the numbers of platelets were decreased significantly. This suggests that menadione and adriamycin decreased turbidity by inducing platelet lysis rather than platelet aggregation. These cellular toxicities induced by menadione or adriamycin was not correlated with oxygen consumption rate but with depletion of protein thiols, suggesting that protein thiols might play an important role in chemical-induced platelet toxicity.
Acute Hepatotoxicity and Toxicokinetics of Acetaminophen in Mice
Toxicological Research, volume 13, issue 3, 1997, Pages 237~245
As the development of a pharmaceutical product is a dynamic process which involves continuousfeed-back between non-clinical and clinical studies, the integration of pharmacokinetics into toxicity testing became increasingly important in recent years. Toxicokinetic measurements in the toxicity studies is considered to be an important scientific approach in the interpretation of the toxicology findings and the promotion of rational study design development. Primarily this research project was conducted to determine the systemic exposure achieved in acute toxicity test and its relationship to dose level and the time course of the toxicity study. Acute hepatotoxicity study and its relevant toxicokinetic study in mice were performed using acetarninophen (AA) as a model compound. The correlation between acute hepatotoxicity indices and toxicokinetic parameters following intraperitoneally administration of various dosages of AA in mice was evaluated and discussed minutely in the text. Based on these studies, single-dose toxicity testing of AA including kinetic studies was evaluated in ICR mice for 7 days and interpreted in the text. Our results from the integration of toxicokinetic monitoring into single-dose toxicity study enable to elucidate the relation of the exposure achieved in toxicity study to toxicological findings and assist in the selection of appropriate dose levels for use in repeated-dose toxicity or later studies.
Superoxide Formation and Cytotoxicity of RAW264.7 Macrophages Induced by Nitric Oxide
Lee, Hong ; Pae, Hyun-Ock ; Jun, Chang-Duk ; Yoo, Ji-Chang ; Park, Rae-Kil ; Chung, Hun-Taeg ;
Toxicological Research, volume 13, issue 3, 1997, Pages 247~250
We have studied cytotoxicity of S-nitroso-N-acetyl- N-DL-penicillamine(SNAP), a Nitric oxide (NO)-releasing compound, in RAW264.7 macrophages. SNAP is cytotoxic to RAW264.7 cells in a concentration-dependent manner. PMA(200 nM) stimulated cells to produce superoxide anton radical(
) and caused a little loss of RAW264.7 cell viability for 12 hr and diminished the cytotoxicity of SNAP. The mechanism by which PMA can protect cells against NO-mediated cytotoxicity was studied by peroxynitrite-enhanced chemiluminescence method. Observed results suggested that
produced by PMAstimulated RAW264.7 cells may quench NO released by SNAP and reduce NO, thus attenuating NO-related damages.
Toxic Effect of Inhaled Toluene on the Neural Cell
Toxicological Research, volume 13, issue 3, 1997, Pages 251~256
Toluene inhalation increases glutamate level and its receptor in various brain regions. In this study, nitric oxide synthase (NOS) activities were investigated in various rat brain regions using NADPH diaphorase staining method which examined histochemical changes of NOS in the neural cells. Also, in vitro LDH leakage assay and MTT test were performed to investigate the toxic influences of toluene in cultured granule cell of rat cerebellum which was significantly affected with toluene in vivo. Rats were exposed to toluene of 10000 ppm for 3 days. 7 days and 14 days by 20 min
2 times a day. NADPH diaphorase staining was processed in the different brain regions after inhalation. NADPH diaphorase staining density was not significantly changed at 3 days inhalation group, but the density decreased in proportion to the duration of toluene inhalation. Over 30% of staining density was decreased at 14 days group which was maximum duration of inhalation in this study. The tendency of staining density decrease was significant in granule cell of cerebellum. Cell death by toluene exposure was observed in cultured cerebellar granule cell.
measured with LDH leakage assay and MTT test were 43 mM and 72 mM respectively.
Covalent Interactions of Reactive Pentachlorophenol Metabolites with Cellular Macromolecules
Toxicological Research, volume 13, issue 3, 1997, Pages 257~263
Pentachlorophenol(PCP) which ks widely used in wood preservation, pulp and paper mills, has led to a substantial envirortmental contamination. To get the reliable data for the effective health risk assessment with PCP, covalent binding potential of PCP to cellular macromolecules and glutathione(GSH) was investigated after intraperitoneal administration of
to rats. PCP metabolites were able to bind covalently to serum albumin and hepatic protein in a dose- and time-dependent manner. Hepatic protein adducts of PCP metabolites were increased as a function of cytochrome P-450 activities, whereas, albumin adducts significantly decreased. Covalent binding of PCP metabolites with DNA or hemoglobin was not observed. GSH levels in liver tissue decreased over 12hrs, however, the level was recovered after 48hrs. Tetrachloro-1,4-benzoquinone (1,4-TCBQ), one of the most reactive PCP metabolites, conjugated with GSH very rapidly. Base on our results, we could conclude that PCP metabolized to reactive electrophilic metabolites by cytochrome P-450 isoenzymes and conjugated rapidly with neighboring protein or nonprotein sulfhydryl before reacting with DNA or hemoglobin. We propose that albumin adducts and mercapturic acids of PCP metabolites can be used good biomarker of recent PCP exposure.
Hepatotoxicity of Uhwangchungsimwon: Acute and Subacute Studies in Rats
Toxicological Research, volume 13, issue 3, 1997, Pages 265~274
Uhwangchungsimwon(UC) is widely used as a herbal medicine on various circulatory disorders in Korea. The objective of this investigation was to characterize the acute, subacute hepatotoxic potency of orally administered UC in rats. In the acute and short-term studies, male rats of 150~170g were gavaged with 0, 7.5 g/kg once daily for up to 1, 5, 10 consecutive days. No differences in body weight, serum enzyme activities, absolute and relative liver weight and histopathological examination on liver between control and UC-fed groups were found. In the subacute study, UC was administered orally to both sexes of rats for 30 days(0, 1.875, 3.75 or 7.5 g/kg/day). There were no-doserelated hepatotoxic signs of general symptoms, body weight gain, water consumption and serum biochemical analysis. Slight decreases of food consumption observed at 3.75 and 7.5 g/kg groups of both sexes were due to be full of UC fed. Gross necropsy and histopathology revealed no evidence of hepatotoxicity related to UC. Our data indicate that hepatotoxicity was not caused by administration of UC up to 7.5 g/kg/dayfor 30 days in rats.
Acute Toxicity of Combined Vaccine (KGCC-95VI) Against Japanese Encephalitis and Hantaan Virus Infection
Shin, Kwang-Soon ; Kim, Chul-Joong ; Yun, Hyo-In ; Park, Jong-Il ; Cha, Shin-Woo ; Shin, Hyeong-Soon ;
Toxicological Research, volume 13, issue 3, 1997, Pages 275~279
The acute toxicity of the combined vaccine (KGCC-95VI) for the prophylaxis against Japanese encephalitis and Hantaan virus infection. recently developed by Korea Green Cross Corporation, was investigated. KGCC-95VI was administered to the Balb /c mice in two routes, orally and subcutaneously, and into the New Zealand White rabbits subcutaneously.
was not accessible as there were no deaths in the group treated even at a dose 800 times the expected clinical dose in both animal species. Between the treated and control groups there were no statistically significant differences in body weight changes and clinical signs during the 14-day observation period, and no pathological gross findings. Accordingly KGCC-95VI is considered not to have the acute toxicity in mice and rabbits.
Subacute Toxicity of Combined Vaccine (KGCC-95VI) Against Japanese Encephalitis and Hantaan Virus Infection in Rabbits
Shin, Kwang-Soon ; Cho, Sung-Hwan ; Yun, Hyo-In ; Kim, Chul-Joong ; Shin, Hyun-Jin ; Nam, Sang-Min ; Park, Young-Mi ; Choi, Eun-Ah ; Kim, Eun ; Youn, Won-Ki ; Sohn, Hwa-Young ; Song, Dong-Ho ; Park, Jong-Il ; Cha, Shin-Woo ; Ahn, Chang-Nam ; Shin, Hyeong-Soon ;
Toxicological Research, volume 13, issue 3, 1997, Pages 281~291
The subacute toxicity of the combined vaccine (KGCC-95VI) for the prophylaxis against Japanese encephalitis and Hantaan virus infection, recently developed by Korea Green Cross Corporation, was investigated. KGCC-95VI was subcutaneously administered into the both sexes of New Zealand White rabbits at the dosage of 0, 10. 50 and 250 ml/kg body weight (20, 100 and 500 times the expected clincal dose) once a day for 30 days. There were no deaths and clinical findings during the experiment period. In both sexes. there were no statistically significant differences between the treated and control groups in urinalysis tests, hematological tests, blood chemistry tests and pathological examinations. The KGCC-95VI is considered not to have the subacute toxicity in the rabbits.
Acute Toxicity of CJ-50001 (rG-CSF) in Rats and Dogs
Toxicological Research, volume 13, issue 3, 1997, Pages 293~296
The acute toxicity study of CJ-50001, a recombinant granulocyte-colony stimulating factor (rG-CSF), was performed in Sprague Dawley (SD) rats and beagle dogs. CJ-50001 was administered up to maximum dose 5,000
/kg (i.v.) and 10,000
/kg (p.o.) in SD rats and 5,000
/kg (i.v.) in beagle dogs. In these experiments, there were no death and harmful clinical changes which were related to CJ-50001. In conclusion,
of CJ-50001 is over 5,000
/kg, i.v. in SD rats and beagle dogs, and over 10,000
/kg, p.o. in SD rats.
Mutagenicity Test on CJ-50001 (rG-CSF)
Toxicological Research, volume 13, issue 3, 1997, Pages 297~301
In order to evaluate the mutagenic potential of CJ-50001 (recombinant human granulocytecolony stimulating factor), 3 sets of mutagenicity tests were performed. In the reverse mutation test using Salmonella typhimurium TA1535, TA1537, TA98 and TA100, CJ-50001 did not increase the number of revertant at any of the concentration tested in this study (500, 250, 125, 62.5 and 31.3
plate). CJ-50001, at the doses of 200, 100 and 50
/ml, did not increase the number of cells having structural or numerical chromosome aberration in cytogenetic test using Chinese Hamster Lung cells. In mouse micronucleus test, no significant increase in the occurrence of micronucleated polychromatic erythrocytes was observed in ICR male mice intraperitoneally administered with CJ-50001 at the doses of 5, 2.5 and 1.25 mg/kg. These results indicate that CJ-50001 has no mutagenic potential in these in vitro and in vivo systems.
Antigenicity of Recombinant Human G-CSF (CJ-50001)
Toxicological Research, volume 13, issue 3, 1997, Pages 303~306
Antigenic potential of genetically engineered human granulocyte colony-stimulating factor (CJ-50001) was assessed in guinea pigs and mice. In active systemic anaphylaxis (ASA) test, although CJ-50001 at 50
/head induced anaphylactic responses, CJ-50001 5
/head alone or 50
/ head with adjuvant did not induce anaphylactic responses. In passive systemic anaphylaxis test (PCA) or passive hemagglutination test (PHA), CJ-50001 did not induce positive responses. It is concluded that, in light of the fact that CJ-50001 was antigenic only in ASA but not in PCA or PHA and also that CJ-50001 is a foreign human recombinant protein to guinea pigs, CJ-50001 may not induce systemic allergic react-ion in its clinical use in human.
Study on Local Irritation of CJ-50001 (rG-CSF) in Rabbits
Toxicological Research, volume 13, issue 3, 1997, Pages 307~310
The local irritation study (skin & occular irritation tests) of CJ-50001, a rG-CSF (recombinant granulocyte-colony stimulating factor) was performed in Japanese White rabbits. CJ-50001 was administered at a dose of 150
/ml, 0.5 ml) to the bare skin and at a dose of 30
/ml, 0.1 ml) to the conjunctival sac of the eye, respectively. In these experiments, there were no clinical signs which were related to CJ-50001 compared with control group. In conclusion, CJ-50001 doesn't have any irritating activity to skin and eye as 0.03% solution.