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REFERENCE LINKING PLATFORM OF KOREA S&T JOURNALS
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The Korean Society of Toxicology
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Volume & Issues
Volume 23, Issue 4 - Dec 2007
Volume 23, Issue 3 - Sep 2007
Volume 23, Issue 2 - Jun 2007
Volume 23, Issue 1 - Mar 2007
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Effects of Lipopolysaccharide on Pharmacokinetics of Drugs
Yang, Kyung-Hee ; Lee, Myung-Gull ;
Toxicological Research, volume 23, issue 4, 2007, Pages 289~299
DOI : 10.5487/TR.2007.23.4.289
Lipopolysaccharide (LPS) endotoxin is an active component in the outer membrane of Gram-negative bacteria. LPS is usually used as an inflammatory animal model. During the inflammation, diarrhea and changes in plasma proteins, in hepatic and/or intestinal microsomal cytochrome P450 (CYP) isozymes, and in the renal and/or biliary excretion of drugs have been reported. Thus, in rats pretreated with lipopolysaccharide endotoxin isolated from Klebsiella pneumoniae (KPLPS rats), the absorption, distribution, metabolism, and excretion of drugs could be expected to be altered. Interestingly time-dependent effects on the hepatic CYP isozymes have been reported in KPLPS rats. Thus, in KPLPS rats, the pharmacokinetics of drugs which are mainly metabolized via CYP isozymes could be expected to be time-dependent. In this review, an attempt to explain changes in pharmacokinetics of drug reported in the literature was made in terms of CYP isozyme changes or urinary and/or biliary excretion changes in KPLPS rats.
Hepatoprotective Effects of Paecilomyces tenuipes Against Carbon Tetrachloride-induced Toxicity in Primary Cultures of Adult Rat Hepatocytes
Hyun, Sun-Hee ; Jeon, Tae-Won ; Lee, Sang-Kyu ; Kim, Chun-Hwa ; Seo, Young-Min ; Kim, Ju-Hyun ; Jeong, He-Min ; Kang, Mi-Jeong ; Lee, Jae-Sung ; Jeong, Tae-Cheon ;
Toxicological Research, volume 23, issue 4, 2007, Pages 301~309
DOI : 10.5487/TR.2007.23.4.301
Paecilomyces tenuipes (PT), one of the Ascomycetes family, has been used for medicinal purposes due to its broad pharmacological activities. The present study was undertaken to investigate the hepatoprotective effects of PT water extracts against
-induced hepatotoxicity in primary cultures of adult rat hepatocytes. When the extract of PT was directly added into the culture medium at 1, 2, and 5 mg/ml, the extracts not only reduce the
-induced elevation of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase, and lipid peroxide, but also protect cultured hepatocytes from
-induced reduction of reduced glutathione, glutathione reductase, glutathione-S-transferase, glutathione peroxidase, catalase and superoxide dismutase. In addition, the effects of PT water extracts on cytochrome P450 enzymes were relatively marginal, indicating that the hepatoprotective effects of PT extract against
-induced toxicity might not be due to the inhibition of
activation. In conclusion, the PT extracts were effective in protecting against
induced hepatotoxicity in hepatocyte cultures, at least in part, by scavenging free radicals, and by modulating enzyme systems involved in cellular oxidative stress.
Effects of Lentinus edodes-powder on Serum Homocysteine Level and Homocysteine-induced Replicative Senescence
Park, Yeong-Chul ; Kim, Min-Hee ; Kim, Jong-Bong ;
Toxicological Research, volume 23, issue 4, 2007, Pages 311~319
DOI : 10.5487/TR.2007.23.4.311
Elevated blood levels of homocysteine (a sulfur-containing amino acid) have been linked to increased risk of cerebrovascular disease including Alzheimer`s disease. A recent study suggests that elevated homocysteine levels may lead to replicative senescence in vitro called `permanent arrest of cell cycle` caused by oxidative stress. In this study, serum homocysteine level in rat was reduced by Lentinus edodes-powder diet, resulting in the reduced level of oxidative stress in rat brain. In addition, homocysteine-induced replicative senescence treated with or without Lentinus edodes-powder was analyzed by population doubling in vitro. The Lentinus edodes-powder induced a increased number of population doubling in primary neuron cell isolated from rat-cerebral cortex. This indicates that Lentinus edodes-powder would delay a homocysteine-induced aging of neuron cells in brain, showing a possible role in preventing cerebrovascular diseases including Alzheimer`s disease.
Chemopreventive Effects of Garlic Extracts on Rat Colonic Aberrant Crypt Foci Induced by 1,2-Dimethylhydrazine
Kim, Tae-Myoung ; Ryu, Jae-Myun ; Kwon, Hyun-Jung ; Hwang, In-Guk ; Ban, Jung-Ok ; Jeong, Heon-Sang ; Hong, Jin-Tae ; Kim, Dae-Joong ;
Toxicological Research, volume 23, issue 4, 2007, Pages 321~330
DOI : 10.5487/TR.2007.23.4.321
Garlic (Allium sativum L.) with the food supplement material and medicine was used traditionally in Asia and Europe. Epidemiological studies revealed that the intake of garlic reduced incidences of various cancer including digestive system. The present study was designed to investigate the effect of garlic ethanol extract on the development of colonic aberrant crypt foci (ACF) induced by 1,2-dimethylhydrazine (DMH) in male F344 rats. Five-week-old rats were given four times for two weeks to subcutaneous injections by DMH (30 mg/kg body weight) to induce ACF. The animals were divided into groups that fed diet containing garlic ethanol extract at five different doses (0.1, 0.2, 0.5, 2, 5%), respectively, animals were evaluated for the total number of ACF and total aberrant crypts (AC) per colon detected from methylene blue-stained rat colon. ACF were formed in animals in DMH-treated group. The feeding suppressed potently the appearance ACF in the colon of rats. Especially, fed diet containing garlic ethanol extract at intermediate dose (0.5%) significantly reduced the number of ACF and AC per colon (p < 0.05). Garlic ethanol extract inhibited DMH-induced overexpression of Activator Protein-1 (AP-1) and
genes related to cell proliferation that also upregulated the expression of p21Waf1/Cip1 mRNA, a cell cycle-regulating gene. These results suggested that garlic ethanol extract may inhibit ACF formation,
gene as the early preneoplastic marker of malignant potential in the process of colon carcinogenesis.
Relative Evaluation for Biocompatibility of Pure Titanium and Titanium Alloys using Histological and Enzymatic Methods
Yeom, Dong-Sun ; Kim, Byung-Il ; Lee, Yu-Mi ; Lee, Eun-Jung ; Yee, Sung-Tae ; Seong, Chi-Nam ; Seo, Kwon-Il ; Cho, Hyun-Wook ;
Toxicological Research, volume 23, issue 4, 2007, Pages 331~339
DOI : 10.5487/TR.2007.23.4.331
Titanium or titanium alloy is a widely used implant material according to its certified biocompatibility, sufficient strength and ready availability. The purpose of this study was to evaluate the relative biocompatibility of titanium and titanium alloy specimens (Ti-29Nb-13Ta, TiNb and Ti-6Al-4V, Ti64) using in vivo and in vitro methods. For in vivo experiment, the specimens were implanted in the abdominal subcutaneous region of female mice for 2 and 4 weeks. The reaction of connective tissue to specimens was evaluated histologically. The specimens were encapsulated by fibrous connective tissue consisting of fibroblast, fibrocyte and other cells including neutrophil, macrophage, giant multinucleated cell and unidentified cells. Some newly formed blood vessels were located in the fibrous capsule surrounding the implant. Cell types and the thickness of fibrous capsules were examined quantitatively. Most of cell types located in the fibrous capsule were fibroblasts and fibrocytes. The average thickness of fibrous capsules for the TiNb specimens was much thinner than that of the titanium alloy, Ti64. The thickness of the fibrous capsule around all titanium specimens decreased at 4 weeks compared to 2 weeks post-implantation. The biocompatibility of titanium and titanium alloy specimens were also investigated in in vitro method using alkaline phosphatase from MG-63 cells. Alkaline phosphatase activity of the TiNb specimen showed higher activity than the titanium alloy, Ti64. In conclusion, the TiNb alloy with thin capsule thickness in vivo and high alkaline phosphatase activity in vitro will be of considerable use in biomedical applications.
The Correlativity of Lipopolysaccharide and Houttuynia cordata Thunb Mixture Extract to Lipid Metabolism
Kwon, Ryun-Hee ; Kang, Kum-Suk ; Kim, In-Deok ; Ha, Bae-Jin ;
Toxicological Research, volume 23, issue 4, 2007, Pages 341~345
DOI : 10.5487/TR.2007.23.4.341
This study was designed to investige the effects of Houttuynia cordata Thunb mixture extract on the lipid metabolism in the lipopolysaccharide (LPS)-induced liver damage of rats. LPS-treatment increased the levels of total-lipid, LDH (lactate, dehydrogenas), triglyceride (TG) and malondialdehyde (MDA). But Houttuynia cordata Thunb mixture extract (HM) pretreatment decreased the levels of total lipid, LDL-cholesterol, TG and MDA. Also LPS-treatment decreased total cholesterol and HDL-cholesterol, but HM-pretreatment increased both of them. These results demonstrated that HM-pretreatment had the preventive effects against the dyfunction of lipid metabolism in the LPS-induced liver damage of rats.
Anti-Oxidative Effects of Rubus coreanum Miquel Extract on Hepatic Injury Induced by Lipopolysaccharide
Kim, In-Deok ; Kang, Kum-Suk ; Kwon, Ryun-Hee ; Ha, Bae-Jin ;
Toxicological Research, volume 23, issue 4, 2007, Pages 347~352
DOI : 10.5487/TR.2007.23.4.347
The protective effects of Rubus coreanum Miquel (RCM) extract against LPS-induced hepatotoxicity were studied in rats. Squrague-Dawley rats were intraperitoneally administered the RCM at 100 mg/kg per day for three weeks. Then single dose of LPS (5 mg/kg) was injected into rats. Four hours later, they were anesthesized with ether and dissected. We examined the levels of glutamate oxaloacetate transaminase (AST), glutamate pyruvate transaminase (ALT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) in sera, superoxide dismutase (SOD) in mitochondrial fraction and catalase (CAT), glutathione peroxidase (GPx) in liver homogenate. LPS-treatment markedly increased the levels of AST, ALT, ALP, LDH and significantly decreased those of SOD, CAT and GPx. But RCM-pretreatment decreased the levels of AST, ALT, ALP and LDH by 57.9%, 37.4%, 62% and 69% respectively and increased those of SOD, CAT and GPx by 82.9%, 64.2% and 96.7% respectively. Subsequently, the protective effects of RCM was evaluated through histopathological examination of liver tissue. The LPS treatment increased the state of necrosis and cirrhosis surrounding the central veins (CV) and sinusoid, but RCM-treatment decreased the state of necrosis and cirrhosis in the liver tissue. These results demonstrated that protective effects of RCM against LPS-induced hepatotoxicity.
Clinical and Toxico-pathological Parameters for Deoxynivalenol Intoxication in B6C3F1 Mice
Kim, Eun-Joo ; Jeong, Sang-Hee ; Ku, Hyun-Ok ; Kang, Hwan-Goo ; Cho, Joon-Hyoung ;
Toxicological Research, volume 23, issue 4, 2007, Pages 353~362
DOI : 10.5487/TR.2007.23.4.353
Deoxynivalenol (DON) is a common food borne mycotoxin and occurs predominantly in grains such as wheat, barley, oats, etc. DON induces systemic health problems such as loss of appetite, emesis and diarrhea in both human and farm animals. Reliable diagnostic parameters for DON intoxication are needed to prevent deep health impact. In order to establish useful diagnostic parameters, we investigated clinical signs, hematological values, serum biochemical values, gross-, histo- and toxico-pathological findings in B6C3F1 male mice after oral administration of DON (0.83, 2.5 and 7.5 mg/kg) for 8 days. Body weight gain was significantly decreased at the highest dose of DON. Anorexia, ataxia, for crudness and lack of vigor were observed at the highest dose DON group. In hematological values, the numbers of WBC and platelets and hemoglobin content were reduced with decreased neutrophil and monocytes by 7.5 mg/kg DON. Prothrombin time (PT) and activated partial thromboplastin time (aPTT) were prolonged in a dose-dependent manner and the content of fibrinogen was elevated at high dose of DON. Of serum biochemical values, total protein, globulin, BUN, cholesterol and test-osterone were reduced but total bilirubin and albumin/globulin ratio increased. The enzyme activity of alkaline phosphatase was decreased while that of alanine aminotransferase was elevated. Relative organ weights of thymus, seminal vesicle/prostate and testes were dose-dependently reduced but those of liver and left adrenal gland increased with dose dependency. As for pathological findings, atrophy of thymus, seminal vesicle/prostate and testes and submucosal edema and ulceration in stomach and depletion of lymphocytes in thymus cortex were observed. In conclusion, these clinical, hematological, blood biochemical and patholgical parameters obtained in the present studies can be used for diagnosis of DON-mycotoxicosis, especially, low WBC, platelets, protein, BUN and testosterone and delayed prothrombin time can be available as for reliable diagnostic parameters.
A Thirteen-week Oral Dose Subchronic Toxicity Study of Isaria sinclairii in Rats
Ahn, Mi-Young ; Han, Jea-Woong ; Jee, Sang-Deok ; Hwang, Jae-Sam ; Hwang, Seok-Jo ; Hong, Yoo-Na ; Kim, Sung-Nam ;
Toxicological Research, volume 23, issue 4, 2007, Pages 363~371
DOI : 10.5487/TR.2007.23.4.363
Isaria sinelairii (IS) was orally administered at doses of 0, 0.04, 0.2, and 1 g/kg/day over a 13-week period. There were no observed clinical signs or deaths related to treatment in all the groups tested. Therefore, the approximate lethal oral dose of I. sinclairii was considered to be higher than 1 g/kg in rats. Throughout the administration periods, no significant changes in diet consumption, ophthalmologic findings, organ weight, clinical pathology (hematology, clinical chemistry, coagulation, and urinalysis) or gross pathology were detected. Minor changes were found in hematological parameters for the 0.04 g/kg/day and 0.2 g/kg/day IS treated groups (triglyceride reductions of
and platelet increases), but all changes were within physiological range. Microscopic examination failed to identify any treatment-related histopathologic changes in the organs of the IS-treated rats other than nuclear enlargement (cellular atypia) of the tubular regions in the medulla of the kidney in the high dose group. From these results, one can conclude that the no-observed effect level (NOAEL) of I. sinclairii is less than 0.04 g/kg/day in rats.
Mouse Single Oral Dose Toxicity Studies of PGB-1, a Novel Polyglucosamine Polymer Produce from Enterobacter sp. BL-2
Lee, Yong-Hyun ; Son, Mi-Kyung ; Jung, Young-Mi ; Kim, Tae-Kwon ; Park, Dong-Chan ; Lee, Hyeung-Sik ; Kim, Pan-Soo ; Ku, Sae-Kwang ;
Toxicological Research, volume 23, issue 4, 2007, Pages 373~382
DOI : 10.5487/TR.2007.23.4.373
This study was conducted to obtain acute information of the oral dose toxicity of PGB-1, a novel polyglucosamine polymer produced from a new strain Enterobacter sp. BL-2 in male and female mice. In order to calculated 50% lethal dose (
) and approximate lethal dose (LD), test material was once orally administered to male and female ICR mice at dose levels of 2000, 1000, 500, 250, 125 and 0 (vehicle control) ml/kg (body wt.). The mortality and changes on body weight, clinical signs, gross observation and organ weight and histopathology of principle organs were monitored 14 days after dosing with PGB-1. We could not find any mortalities, clinical signs, body weight changes and gross findings. In addition, significant changes in the organ weight and histopathology of principal organs were not observed except for some sporadic findings. The results obtained in this study suggest that PGB-1 may not be toxic in mice and may be therefore safe for clinical use. The
and approximate LD in mice after single oral dose of PGB-1 were considered over 2000 mg/kg in both female and male mice.
Intravenous Single and Two Week Repeated Dose Toxicity Studies of Rice Cells-derived Recombinant Human Granulocyte-Macrophage Colony Stimulating Factor on Rats
Ji, Jung-Eun ; Lee, Jung-Min ; Choi, Jong-Min ; Choi, Young-Hwa ; Kim, Seok-Kyun ; Ahn, Kyong-Hoon ; Lee, Dong-Hoon ; Kim, Ha-Hyung ; Han, Kyu-Boem ; Kim, Dae-Kyong ;
Toxicological Research, volume 23, issue 4, 2007, Pages 383~389
DOI : 10.5487/TR.2007.23.4.383
Recombinant human granulocyte-macrophage colony stimulating factor (hGM-CSF) regulates proliferation and differentiation of hematopoietic progenitor cells and modulates function of the mature hematopoietic cells. In the previous study, we reported that hGM-CSF could be produced in transgenic rice cell suspension culture, termed rhGM-CSF. In the present study we examined the single and repeated dose toxicity of rice cells-derived hGM-CSF in SD rats. During single dose toxicity study for 7 days, there were no any toxic effects at any dose of from 10 to
. The lethal dose (
) was not found in this range. Moreover, repeated dose toxicity study of 14-days period and at the doses of 50 and
(i. v.) of rhGM-CSF did not show any changes in food and water intake. There were also no significant changes in both body and organ weights between the control and the test groups. The hematological and blood biochemical parameters were statistically not different in all the groups. These results suggest that rhGM-CSF has no toxicity in SD rats.
Repeated Dose and Reproductive/Developmental Toxicities of Acetanilide in Rats
Chung, Moon-Koo ; Baek, Sung-Soo ; Lee, Sang-Hee ; Kim, Hyun-Mi ; Choi, Kyung-Hee ; Han, Sang-Seop ;
Toxicological Research, volume 23, issue 4, 2007, Pages 391~403
DOI : 10.5487/TR.2007.23.4.391
The study was conducted to assess the repeated dose and reproduction and developmental toxicities of acetanilide, an intermediate for drug production, as a part of OECD Screening Information Data Set (SIDS) program. The test agent was administered by gavage at dose levels of 0, 22, 67, 200 and 600 mg/kg to Sprague-Dawley rats (12/group/sex) during pre-mating and mating period for males(up to 30 days) and females and pregnancy and early lactation period for females (up to 39-50 days). At 22 mg/kg, decreases in HGB, HCT (males) and MCHC (females), hyperplasia of spleen red pulp, hyperplasia of femur bone marrow (both sexes) were observed. At 67 mg/kg, salivation (males), reduced food consumption (both sexes), decreases in RBC, HGB, HCT and MCHC (males), increases in MCV (males) and spleen weight (males), hyperplasia of spleen red pulp and femur bone marrow (both sexes) were observed. At 200 mg/kg, decreases in locomotor activity and salivation (both sexes), reduced food consumption (both sexes), decreases in RBC, HGB, HCT and increases in MCV, MCH, BUN, T-BIL (males), enlargement of spleen (both sexes), increased weight of spleen (males), hyperplasia of spleen red pulp and femur bone marrow and extramedullary hematopoiesis of liver (both sexes), atrophy of thymus and corpus luteum hyperplasia of ovary (females) were observed. At 600 mg/kg, decreases in locomotor activity, cyanosis (both sexes), reddish tear, and salivation (males), mortality (4 out of 12 females), decreased body weight (females), reduced food consumption (both sexes), decreases in RBC, HGB, HCT and MCHC and increases in WBC, MCV, MCH, reticulocyte, neutrophil, lymphocyte, monocyte, AST, ALT, BUN, T-BIL, ALB, Ca and A/G ratio (males), enlargement of spleen, increased weights of spleen (both sexes), liver (males), kidney and ovary, decreased weights of thymus (females), hyperplasia of spleen red pulp, hyperplasia of femur bone marrow and extramedullary hematopoiesis of liver (both sexes), and atrophy of thymus and corpus luteum hyperplasia of ovary (females) were observed. Regarding the reproduction and development toxicities, there were no treatment-related changes in precoital time, mating index, fertility index and pregnancy index at all doses tested. At 22 and 67 mg/kg, there were no adverse effects on all the parameters observed. At 200 mg/ kg, decreased body weight of pups (day 4 p.p.) were observed. At 600 mg/kg, decreased body weight of pups (day 0 and 4 p.p.) and viability index (day 4 p.p.), increased incidence of newborns dead or with abnormal clinical signs were observed. The results suggest that the NOAELs for general toxicity are < 22 mg/kg, LOAELs are 22 mg/kg and the NOAELs for reproductive toxicity are 67 mg/kg.
Single-Dose Toxicity and Four Week Repeated-Dose Toxicity Study on Tensolin-F
Kim, Keun-Su ; Park, Sung-Min ; Lee, Nam-Jin ; Pyo, Hyeong-Bae ; Chai, Hee-Yul ; Jung, Yu-Ri ; Lin, Chun-Mai ; Kim, Sun-Hee ; Lee, Hye-Young ; Kang, Jong-Koo ;
Toxicological Research, volume 23, issue 4, 2007, Pages 405~413
DOI : 10.5487/TR.2007.23.4.405
This study was to investigate single and repeated-dose toxicities of Tensolin-
, an anti-wrinkle agent, in Sprague-Dawley (SD) rats or ICR mice. In single-dose oral toxicity study, the test materials were administered once by gavage to male and female SD rats at dose levels of 0 and 2,000 mg/kg. No dead animals and abnormal necropsy findings were found in control and Tensolin-
treated group. Therefore, the approximate lethal dose of Tensolin-
was considered to be higher than 2,000 mg/kg in rats. In the 4-week repeated oral toxicity study, the test material was administered once daily by gavage to male and female ICR mice at dose levels of 0, 25, 50 and 100 mg/kg/day for 4-weeks. In the results, no abnormality was observed in mortality, clinical findings, body weight changes, food and water consumptions, opthalmoscopic findings, necropsy findings, histopathological findings. In hematological analysis, there was a trend of increase in reticulocyte at male 25 mg/kg, although such changes were in normal ranges. On the other hand, there was a trend of decrease in hemoglobin at female 50, 100 mg/kg, such changes were in normal ranges. In addition, serum biochemical parameters including sodium, BUN and chloride increased at 25, 50 and 100 mg/kg. Relative organ weights of right testis, brain, lung and left epididymis were increased in 100 mg/kg groups of male rats in contrast to not change in female groups. However, these changes of relative organ weights, hematological and serum biochemical parameters were not accompanied with related signs such as histopathological changes or clinical findings. In conclusion, 4-week repeated oral dose of Tensolin-
to ICR mice did not cause apparent toxicological change at the dose of 25, 50, 100 mg/kg body weight. Consequently the no-observed-adverse-effect level (NOAEL) for Tensolin-
in ICR mice following gavage for at least 4-week is higher than 100 mg/kg/day.