• Molecular & Cellular Toxicology
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• v.5 no.1
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• pp.32-43
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• 2009

Acetaminophen (APAP) overdose is known to cause severe hepatotoxicity mainly through the depletion of glutathione. In this study, we compared the cytotoxic effects of APAP on both a normal murine hepatic cell line, BNL CL.2, and its SV40-transformed cell line, BNL SV A.8. Gene expression profiles for APAP-treated cells were also obtained using microarray and analyzed to identify differences in genes or profiles that may explain the differences of susceptibility to APAP in these cell lines. These two cell lines exhibited different susceptibilities to APAP (0-$5,000{\mu}M$); BNL SV A.8 cells were more susceptible to APAP treatment compared to BNL CL.2 cells. A dose of $625{\mu}M$ APAP, which produced significant differences in cytotoxicity in these cell lines, was tested. Microarray analysis was performed to identify significant differentially expressed genes (DEGs) irrespective of APAP treatment. Genes up-regulated in BNL SV A.8 cells were associated with immune response, defense response, and apoptosis, while down-regulated genes were associated with catalytic activity, cell adhesion and the cytochrome P450 family. Consistent with the cytotoxicity data, no significant DEGs were found in BNL CL.2 cells after treatment with $625{\mu}M$ APAP, while cell cycle arrest and apoptosis-related genes were up-regulated in BNL SV A.8 cells. Based on the significant fold-changes in their expression, a genes were selected and their expressions were confirmed by quantitative real-time RT-PCR; there was a high correlation between them. These results suggest that gene expression profiles may provide a useful method for evaluating drug sensitivity of cell lines and eliciting the underlying molecular mechanism. We further compared the genes identified from our current in vitro studies to the genes previously identified in our lab as regulated by APAP in both C57BL/6 and ICR mice in vivo. We found that a few genes are regulated in a similar pattern both in vivo and in vitro. These genes might be useful to develop as in vitro biomarkers for predicting in vivo hepatotoxicity. Based on our results, we suggest that gene expression profiles may provide useful information for elucidating the underlying molecular mechanisms of drug susceptibility and for evaluating drug sensitivity in vitro for extrapolation to in vivo.

• Journal of Life Science
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• v.20 no.9
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• pp.1409-1414
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• 2010

The aim of this study was to investigate the effects of exercise on intrinsic and extrinsic apoptosis signaling pathways in skeletal muscle. ICR-type white male mice were divided into a control group (CON: n=10) and an exercise training group (EX: n=10) after a 1 week adaptation period. EX performed treadmill running at 16.4 m/min with a 4% incline, 40 min/day and 5 days/week for 8 weeks. Cervical dislocation was performed at 48 hours after the last bout of exercise, after which gastrocnemius skeletal muscles were immediately collected. The results of verifying the intrinsic apoptosis pathway showed that there were no significant differences in Bcl-2, Bax, or the ratio of Bax/Bcl-2 proteins between EX and CON. On the other hand, the results of verifying the extrinsic apoptosis pathway showed that caspase-8 proteins were significantly lower in EX than in CON (p<0.05). Apoptosis suppressing protein HSP70 was higher in EX than in CON. In addition, caspase-3, which is the final factor for apoptosis, was not activated. These results indicate that apoptosis did not develop since caspase-3 is non-cleaved by the effects of caspase-8 and HSP70 extrinsic pathways rather than Bcl-2 and Bax intrinsic pathways among signal pathways for apoptosis.

• Journal of Dairy Science and Biotechnology
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• v.34 no.2
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• pp.83-89
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• 2016

This study was designed to determine the mutagenic potential of hydrolyzed glycomacropeptide (GMP) powder (hereafter referred to as 23%-GNANA; product name: HELICOBACTROL-23) in a micronucleus test using bone marrow in ICR mice. Three experimental groups were used: a 3-step concentration group, with a maximum concentration of 2,000 mg/kg, and other sequentially two-fold lower concentrations, a negative control group, and a positive control group. The test material was administered for 2 d to observe the frequency of micronucleus formation up to 48 h after the test material was absorbed by the body. When the polychromatic erythrocyte (PCE) content of erythrocytes was compared, no significant differences were noted between the negative control group and the test group (p<0.05). Similarly, when the average numbers of micronucleated PCE (MNPCE) in 2,000 PCE per animal were compared, no significant difference was observed between the negative control group and the test group (p<0.05). No dose-response relationship with regard to the concentration of the test material administered was noted. These results allow us to conclude that hydrolyzed whey protein powder does not cause formation of micronuclei in mouse bone marrow cells under the applied conditions. In this study, the average frequency of micronucleus formation in PCE was significantly higher in the positive control group compared with the negative control group; thus, the test conditions were appropriate for detecting the frequency of micronucleus formation induced by the test material. In conclusion, the safety of 23%-GNANA test substance was verified in an in vivo micronucleus test in mice, conducted before the registration of HELICOBACTROL-23 as a food additive.

• Applied Microscopy
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• v.34 no.3
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• pp.185-197
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• 2004

To investigate the effect of the squalene against the lead toxicity and recovery of renal failure. Healthy male ICR mice were used for experiment. The activity of nitric oxide (NO) was observed after the intraperitoneal injection in mice. The ultrastructural changes of the kidney were observed after the intraperitoneal injection of lead acetate in mice. The experimental groups were divided into three groups. Group 1 was normal mouse. Group 2 was not treatment with squalene after intraperitoneal contamination of lead acetate (30 mg/kg). And, Group 3 was injected squalene (180 mg/kg) after intraperitoneal contamination of lead acetate. All groups were used to 10 mice. The results were as follow: In the case of the group 2, swelling of the outer membrane and destruction of the inner membrane (cristae) of the mitochondria, dripping of the ribosomes from the rough endoplasmic reticulum were happened at 24 hours and 48 hour. These were gradually reparied after 72 hours. In the case of the group 3, damages of the mitochondria and the rough endoplasmic reticulum were showed less than the group 2 at 24 hours. Especially, after 48 hours, these were almost same as the group 1. In the case of group 2, the level of NO was decreased. However, In the case of group 3, the level of NO was increased more than normal as well as repaired the decreased NO level by Pb (P<0.05). It was concluded that the squalene was the protective and recovery effects for the toxicity of the lead in the renal proximal tubules.

• Parasites, Hosts and Diseases
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• v.35 no.4
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• pp.245-250
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• 1997

The responses of gastric mucosal mast cells (GMMCS) to infection with coccid- ian protozoa, Clptosporinium muris, in mice were examined during primary and challenge infections. Each of three-week-old ICR SPF mice was orally inoculated with a single dose of 2 × 106 oocysts of C. muffs (strain MCR). After oocyst shedding ceased, the mice were orally challenged with a single dose of 2×106 oocysts of the same species. GMMCS reached a peak on days 20-30 postinoculation (Pl) in number, and decreased thereafter. An increase on days 20-30 post-challenge-infection (PCI) was also observed. The mice showed, on the whole, normal profiles of oocyst shedding in droppings. The number of the cells of uninfected control mice remained constant. .Tudging from the above results, it is suggested that mastocytosis correlate with expulsion of C. mans in primary infection and the defense mechanism of challenge infection.

• THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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• v.9 no.1
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• pp.1-14
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• 2003

Objective : Ikiyangeumhaedoc-tang(IYHT) has an effect of nourishing Yin(陰) and Jin(津), and has been used to cancer patient effectively. In order to prove the anticancer's and antimetastic effect of IYHT experimentally, studies were done. Methods : We evaluated the cytotoxic activity on HT-1080 cells as well as inhibitory effect on activity of DNA topoisomerase Ⅰ, cell adhesion, cell invasion and proliferation of HUVEC cells induced by bFGF and measured the expression of mRNA(uPA, MMP2, TIMP2), p-ERK protein, recovery effect of gap junctional intercellular communication by $H_{2}O_2$ and survival time of ICR mice bearing sacoma-180. Results : IYHT showed the inhibitory effect on DNA topoisomerase Ⅰ in the concentration of $100{\mu}g/ml,\;500{\mu}g/ml$ and the dosage-dependent inhibitory effect on the adhesion of HT-1080. The concentration of 1mg/ml of IYHT inhibited 15% of adhesion compared with control. IYHT decreased the expression of uPA, but not in MMP2, TIMP2 by RT-PCR and inhibited the expression of p-ERK effectively in the concentration of more than $500{\mu}g/ml.$ IYHT recovered the inhibited gap junctional intercellular communication by $H_{2}O_2$ to the level of 60% of normal control in the concentration of $400{\mu}g/ml$ but, did not extended the mean survival time of sarcoma 180-bearing mouse. Conclusions : It was concluded that IYHT could be applied usefully for prevention and treatment of human cancer, And also experimental study for the evaluation of molecular biological study and antimetastatic research would be recommended in the near future.

• Journal of the Korean Society of Food Science and Nutrition
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• v.24 no.2
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• pp.195-201
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• 1995

In this study we wanted to investigate the effect of taurine supplement on the lipid peroxide formation and the activities of glutathione(GSH) dependent enzyme in diabetic model mice. We induce type I diabetes mellitus with alloxan injeciton in ICR mice and type II with high calorie diet in genetically hyperglycemic KK mice. Taurine was given in drinking water at the level of 5%(w/v) for seven days. In type I diabetic model, the malondialdehyde(MDA) of liver and islet significantly increased compared to control group and they significantly decreased by taurine supplement. In type II diabetic model, the concentration of MDA was not changed by taurine supplement. The activities of GSH-peroxidase(GPX) of liver and islet increased in type I diabetic group while decreased in type II. GPX activities were not changed by taurine supplement in the liver of both types but increased in the islet of type II. Taurine supplement has no effect on the activities of GSH S-transferase(GST) in both types. From these results, we suggest that taurine supplement protect against lipid peroxide formation in diabetic model of type I.

• Journal of the Korean Society of Food Science and Nutrition
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• v.36 no.5
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• pp.521-526
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• 2007

The effects of red ginseng powder on hepatotoxicity in $benzo(\alpha)pyrene\;[B(\alpha)P]$-treated mice were investigated. Male ICR mice were pretreated with red ginseng powder (50 or 100 mg/kg/day, for 5 days, intraperitoneally) before treatment with $B(\alpha)P$ (0.5 mg/kg, i.p, single dose). The ability of red ginseng powder to protect against oxidative damage to the mouse liver was examined by determining the level of lipid peroxide, glutathione, and the antioxidant enzyme activities. The glutathione content depleted by $B(\alpha)P$ were significantly increased by red ginseng powder, but elevation of lipid peroxide content induced by $B(\alpha)P$ was decreased by red ginseng powder. The increased activities of superoxide dismutase, catalase and glutathione peroxidase after $B(\alpha)P$-treatment were decreased by the treatment of red ginseng Powder; however, glutathione S-transferase activity depleted by $B(\alpha)P$ were significantly increased. These results suggest that red ginseng powder can protect against $B(\alpha)P$ intoxification through its antioxidant properties.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.20 no.4
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• pp.293-299
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• 1987

At various times and places all over the world men have become ill and some have died after eating shellfish that were intoxicated with paralytic shellfish poison(PSP) caused by Protogonyaulax spp. In late March, 1986, two persons were dead by ingesting wild sea mussels, Mytilur edulis, grown at bottom of an anchored waste ship to be dismantled at Gamchun Bay, Pusan, Korea. The samples were collected from the bottom of the ship during April $1\~April$ 8 of the year to find the cause of the food poisoning accident. The toxicity was estimated by bioassay with ICR male mouse, while the toxins were extracted and characterized. The toxins were extracted with acidified $80\%$ ethanol. The extract was defatted three times with dichloromethane, treated with activated charcoal, and then purified by chromatography on Bio-Gel P-2 and Bio-Rex 70. The toxic fractions obtained were analysed by cellulose acetate membrane electrophoresis, thin layer chromatography and high performance liquid chromatogaphy. The range and the average of PSP-toxicity of the samples were $132\~295\;MU/g$, 203 MU/g respectively. The amount of PSP was $26.4\~58.9{\mu}g/g$ of whole meat in range and $40.6{\mu}g/g$ in average. The toxicity of the digestive gland of the samples was 9 times higher than that of edible meat (except digestive gland) as $439\~979MU/g$, and it was about $70\%$ in total toxin. The compositional analytical results of the paralytic shellfish toxin, Gonyautoxin $1\~4$ were the major part of the PSP and Saxitoxin and neosaxitoxin were detected as the minor component. It was concluded that the food poisoning accident was caused not by Saxitoxins but by Gonyautoxins.

• Current Research on Agriculture and Life Sciences
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• v.31 no.1
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• pp.51-55
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• 2013

Licorice, Glycyrrhizae radix, is one of the oldest and most frequently used botanicals in the oriental medicine. Our previous study showed that dehydrolyasperin C (DGC) isolated from licorice had antioxidant activity and induced phase 2 detoxifying enzymes in mouse hepatoma cells. Therefore, this study was conducted to investigate the effect of exposure time to DGC on quinone reductase (QR), one of the anticarcinogenic biomarkers, and antioxidant potential of plasma using animal model. ICR mice were divided into 7 groups, in which mice in each group were injected with DGC (5 mg/kg b.w.) for 0, 2, 4, 6, 8, 12, 24 hours respectively. Following the treatment the organs including liver, kidney, lung, stomach, large intestine, small and large intestines were collected and subjected to QR activity assay, western blotting, and FRAP assay. Exposure to DGC caused a significant induction of QR activity in stomach and large intestine of mice. Ferric reducing activity of plasma, a typical biomarker for antioxidative potentialshowed that DGC improved antioxidant potential in mice. However, no significant effect of DGC was observed in the other organs.