• Journal of Pharmacopuncture
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• v.5 no.1 s.8
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• pp.7-26
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• 2002

Objective: The purpose of this study was to investigate acute and subacute toxicity and sarcoma-180 anti-cancer effects of herbal acupuncture with Carthami- Tinctorii fructus (CF) in mice and rats. Method: Balb/c mice were injected intraperitoneally with Carthami - Tinctorii fructus (CF) for $LD_{50}$ and acute toxicity test. Sprague Dawley rats were injected intraperitoneally with Carthami- Tinctorii fructus (CF) for subacute toxicity test. The Carthami- Tinctorii fructus herbal-acupuncture was injected on Chung-wan (CV12) of mice with Sarcoma-180 cancer cell line. Results: 1. $LD_{50}$ was uncountable as none of the subjects expired during the test. 2. In acute toxicity test, toxic symptoms were not detected, but the body weight of mice was increased in treatment Ⅰ, treatment Ⅱ groups, compared to the normal group.(p<0.05) 3. In acute toxicity test of serum biochemical values of mice, glucose was increased in treatment Ⅰ and treatment Ⅱ groups, total cholesterol was increased in treatment I group, GOT was decreased in treatment Ⅱ group, and GPT was decreased in treatment Ⅰ group, compared to the normal group.(p<0.05) 4. The clinical signs and the body weight of mice treated with 0.1 cc, 0.2cc Carthami- Tinctorii fructus (CF) were not affected during the subacute toxicity test. 5. In subacute toxicity test, treatment groups didn't show significant changes in complete blood count test (CBC) of rats, compared to the nonnal group.(p<0.05) 6. In subacute toxicity test of serum biochemical values of rats, uric acid was decreased in treatment Ⅰ and treatment Ⅱ groups, compared to the nonnal group, triglyceride was decreased in treatment I group, compared to the normal group, GOT and GPT were decreased in treatment I and treatment Ⅱ groups, and alkaline phosphatase was decreased in treatment Ⅰ and treatment Ⅱ groups, compared to the normal group.(p<0.05) 7. Median survival time was increased in all the treatment groups for Sarcoma-180 cancer cell treated with Carthmni- Tinctorii fructus (CF).(p<0.05) 8. Natural killer cell activity was significantly increased in all the treatment groups compared to the normal group.(p<0.05) 9. Interleukin-2 productivity was decreased in treatment Ⅰ and treatment Ⅱ groups.(p<0.05) Conclusion: According to the results, we can conclude herbal-acupuncture of Carthami-Tinctoriifructus (CF) caused negligible toxkity, and had anti-tumor effects in mice.

• Journal of Pharmacopuncture
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• v.5 no.2
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• pp.120-136
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• 2002

Objectives : The purpose of this study is to investigate Acute and Subacute Toxicity, and Anti-cancer Effect of H Herbal-acupuncture on mice and rats. Methods : Balb/c mice were injected intraperitoneally with H Herbal-acupuncture for $LD_{50}$ and acute toxicity test. Sprague-Dawley rats were experimented in the same way for subacute toxicity test. H Herbal-acupuncture was injected into abdomen of mice having S-180 cancer cell line. Result : 1. During the test, $LD_{50}$ could not be counted since there was no expired subjects. 2. In an acute toxicity test, the loss of motility and reflex action was observed, but weight increased in the treatment group, compared with those in the normal group (P<0.05). 3. In an acute toxicity test of serum biochemical values of mice, glucose increased in the treatment group II while total cholesterol was increased in the all treatment groups (P<0.05). 4. In a subacute toxicity test, a little loss of motility and reflex action was observed in the treatment group. Weight of mice in the treatment group decreased on the 28th day. 5. In a subacute toxicity test, liver weight was decreased but lung weight of mice increased in the all treatment groups (P<0.05). 6. As a result of measuring Complete Blood Count test (CBC) of rat, HCT was decreased in treatments even though it was not significant, compared with the normal group (P<0.05). 7. In a serum biochemical value test of subacute toxicity, total protein and albumin decreased in the all treatment groups. Creatinine, glucose, GOT increased in the treatment group I compared with the control group. Alkaline phos-phatase decreased in treatment II group, compared with the control group (P<0.05). 8. Median survival time that was measured in the rats treated with sarcoma-180 cancer cell Median decreased in the treatment group, compared with the control group (P<0.05). 9. Natural killer cell activity showed significant reduction at 100:1 and 10:1 E/T ratio while it increased at 50:1 E/T ratio. It is inferred that there was an error in the experiment (P<0.05). 10. In an interleukin-2 productivity test, even though it decreased in lung cancer, and increased in abdomen cancer, but it was only a small difference (P<0.005). 11. After injecting B16F10 cell into a capillary vessel of C57BL/6 mice and generating metastasized lung cancer, the lung was examined with the naked eye. It was not possible to see metastasized cancer in the all groups on the seventh day but the cancer was viewed on the fourteenth day. The number and volume of metastasized cancer in the treatment group enlarged in the treatment group, compared with the control group. Conclusion : According to the results, H herbal-acupuncture took no effects in cancer.

• Journal of Pharmacopuncture
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• v.6 no.2
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• pp.7-27
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• 2003

Objective : The purpose of this study was to investigate acute and subacute toxicity and sarcoma-180 anti-cancer effects of herbal acupuncture with cultivated wild ginseng (distilled) in mice and rats. Method : Balb/c mice were injected intravenous with cultivated wild ginseng herbal acupuncture for $LD_{50}$ and acute toxicity test. Sprague-Dawley rats were injected intravenous with cultivated wild ginseng herbal acupuncture for subacute toxicity test. The cultivated wild ginseng herbal-acupuncture was injected at the tail vein of mice. Results : 1. In acute $LD_{50}$ toxicity test, there was no mortality thus unable to attain the value. 2. Examining the toxic response in the acute toxicity test, there was no sign of toxication. 3. In acute toxic test, running biochemical serum test couldn't yield any differences between the control and experiment groups. 4. In subacute toxicity test, there was no sign of toxication in the experimental groups and didn't show any changes in weight compared to the normal group. 5. In subacute toxicity test, biochemical serum test showed significant increase of Total albumin, Albumin, and Glucose in the experimental group I compared with the control group. Significant decrease of GOT, ALP, GPT, and Triglyceride were shown. In experiment group II, only Glucose showed significant increase compared with the control group. 6. Measuring survival rate for anti-cancer effects of Sarcoma-180 cancer cell line, all the experimental groups showed significant increase in survival rate. 7. Measuring NK cell activity rate, no significant difference was shown throughout the groups. 8. Measuring Interleukin-2 productivity rate, all the experimental groups didn't show significant difference. 9. For manifestation of cytokine mRNA, significant decrease of interleukin-10 was witnessed in the experimental group compared to the control group. Conclusion : According to the results, we can conclude cultivated wild ginseng herbal acupuncture caused negligible toxicity, and had anti-tumor effects in mice.

• Korean Journal of Clinical Pharmacy
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• v.14 no.2
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• pp.61-70
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• 2004

Heptaplatin is a new platinum derivative with antitumor activity against gastric cancer. Preclinical studies showed that it is less toxic than other platinum analogues. The purpose of this study is to evaluate the efficacy and toxicity of the combination therapy of heptaplatin and 5-fluorouracil in Korean advanced gastric cancer patients. This study was investigated retrospectively. The patients group consisted of 65 advanced gastric cancer patients with no prior radiotherapy. All patients received heptaplatin $400\;mg/m^2$ by 2-3 hour infusion on Day 1 and 5-FU $1000\;mg/m^2by 12-24 hour continuous infusion for 5 days. After the first cycle, subsequent doses were adjusted according to the toxicity. Courses were repeated every 28 days. As results, objective response occurred in 16 patients $(24.6\%)$. Two were complete and 14 were partial response. Median progression free survival was 32 weeks with $29\%$ of patients progression free at 1 year. The most common hematologic toxicity was anemia. Grade 3 or 4 anemia was seen at $2.7\%$ of treatment cycles. Grade 3 or higher leucopenia was seen at $1.2\%$ of cycles. Grade 3 or 4 neutropenia and thrombocytopenia occurred at $6.1\%\;and\;1.5\%$ of cycles, respectively. The most common nonhematologic toxicity was proteinuria. Though no patients experienced grade 3 or 4 proteinuria, proteinuria was a considerable factor for this chemotherapy. Grade 3 or higher gastrointestinal toxicities were nausea and vomiting ($4.6\%$ of patients) and diarrhea ($1.5\%$ of patients). Grade 2 renal toxicity with elevation of serum creatinine was seen in $0.3\%$ of cycles, which is less than that of other platinum analogues. This study showed that combination therapy of heptaplatin and 5-FU have modest antitumor activity against advanced gastric cancer without severe renal toxicity.

• Environmental Mutagens and Carcinogens
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• v.21 no.2
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• pp.156-163
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• 2001

Vanadium has been known as environmental polluants resulted from the burning of fossil fuels in nature. It led to toxic responses by prooxidant activity, inducing free radicals and the accumulation in the tissues. Recently, there has been growing interest in an essential nutritional requirement of vandium and especially the treatment of diabetes. But because of its strong toxicity, thease chemicals have narrow safety margin. In order to reduce metal toxicity, and increase absorption and biological activities, metal ions such as selenium and chromium were uptaken in yeast cells. In this study, Vanadium yeast was prepared by uptaking vanadate in yeast cells. Vanadate induced hematological and biochemical changes in the experimental rat blood were inhibited by the treatments of vanadium yeast. Lipid peroxidation and catalase activity were significantly increased in kidney and liver after a single intraperitoneal injection of vanadate to rats. However, these observations were apparently reduced in the vanadium yeast treated group. Vanadium amount in blood, kidney and liver after a single intraperitoneal injection of vanadium yeast was significantly reduced than that of vanadate treated group. In conclusion, vanadium yeast uptaken vanadate in yeast cells could reduce toxic effects of vanadate.

• Korean Journal of Pharmacognosy
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• v.31 no.2
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• pp.216-223
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• 2000

The anti-inflammatory activity of SEO-KYONG-TANG extract(SKTWE) was examined by using carrageenin- and acetic acid-induced edema, croton oil-induced granuloma pouch, and adjuvant arthritis in rats. In addition, the acute toxicity, analgesic and antipyretic effects of SKTWE were investigated by using general experimental methods in mice. SKTWE did not show acute toxicity at 2400 mg/kg(p.o.) nor 1200 mg/kg(i.p.). After oral administration of the SKTWE to rats, significant anti-inflammatory activity was observed on 1% carrageenin- and 5% acetic acid-induced edema. Also, it significantly inhibited granuloma and exudation in these. In the adjuvant arthritis experiment, the SKTWE decreased the hind paw edema after 3 days of oral administration. In addition, it inhibited the writhing syndromes induced by 0.7% acetic acid in mice. The antipyretic activity of SKTWE was also observed through the typhoid vaccine experiment. These results suggest that SKTWE has analgesic, anti-inflammatory and antipyretic action.

• Journal of Environmental Health Sciences
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• v.22 no.3
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• pp.8-16
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• 1996

Effects of water extract of aloe vera on lead-induced neurotoxicity were investigated in sciatic nerve isolated from rat. The mechanism on toxicity reduction by measuring activities of axonal enzymes, metabolism of myo-inositol in nerve, lead concentration in several organs and so on were further examimed. In the lead-treated rats, the transport rate of axonal enzyme, such as acetyl cholinesterase and choline acetyltransferase, was reduced by from 50% to 30% respectively. Reduction in myo-inositol concentration and $Na^+/K^+$ ATPase activity were also observed in sciatic nerve from lead-treated rat. However, the aloe extract administration significantly eliminated the impairment and maintained myo-inositol concentration to about 85% of normal level. Also aloe extract promoted the excretion rate of lead which is accumulated in blood, sciatic nerve and kidney. These results suggest that lead-induced neurotoxicity was significantly reduced by administration of aloe extract and the mechanism might be partly increase in kidney excretion rate of lead and parity normalization of $Na^+/K^+$ ATPase activity which is critical factor in order to keep nerve maintaining normal myo-inositol level.

• Environmental Analysis Health and Toxicology
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• v.13 no.3_4
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• pp.117-123
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• 1998

Paraquat is a useful nonselective herbicide widely used throughout the world. However, accidental or intentional ingestion of the paraquat cause fetal pulmonary injuring. But there is not suitable antidote of paraquat intoxication and therapeutic agents now be used are not effective. So, in this study we intended to evaluate the inhibitory effects of DDB(dimethyl-4,4'dimethoxy-5,6,5',6'-dimethylene dioxyphenyl-2,2'-dicarboxylate) on paraquat toxicity. DDB (100mg/kg) was administered orally to SD rats lhr after paraquat(50mg/kg) injection. After 24 hours, the biochemical parameters of blood and tissues were examined. In paraquat treated groups sGPT, sGOT, BUN, creatinine, MDA and alkaline phosphatase levels in blood and MDA, glucose-6-phosphatase activity in tissues were elevated by 2 to 5 times of normal values. However in schizandrin treated groups, sGPT, sGOT, MDA and alkaline phosphatase activity in blood and MDA and glucose-6-phosphatase activity were significantly decreased to notmal levels but not in biochemical parameters of nephrotoxicity, BUN and creatinine levels. Therefore, we concluded that schizandrin can be used as an antidote of pulmono, hepatotoxicity of paraquat.

• BMB Reports
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• v.34 no.5
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• pp.402-407
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• 2001

Based on the currently proposed toxicity model for the different Bacillus thuringiensis Cry $\delta$-endotoxins, their pore-forming activity involves the insertion of the ${\alpha}4-{\alpha}5$ helical hairpin into the membrane of the target midgut epithelial cell. In this study, a number of polar or charged residues in helix 4 within domain I of the 65-kDa dipteranactive Cry11A toxin, Lys-123, Tyr-125, Asn-128, Ser-130, Gln-135, Arg-136, Gln-139 and Glu-141, were initially substituted with alanine by using PCR-based directed mutagenesis. All mutant toxins were expressed as cytoplasmic inclusions in Escherichia coli upon induction with IPTG. Similar to the wild-type protoxin inclusion, the solubility of each mutant inclusion in the carbonate buffer, pH 9.0, was relatively low When E. coli cells, expressing each of the mutant proteins, were tested for toxicity against Aedes aegypti mosquito-larvae, toxicity was completely abolished for the alanine substitution of arginine at position 136. However, mutations at the other positions still retained a high level of larvicidal activity Interestingly, further analysis of this critical arginine residue by specific mutagenesis showed that conversions of arginine-136 to aspartate, glutamine, or even to the most conserved residue lysine, also abolished the wild-type activity The results of this study revealed an important determinant in toxin function for the positively charged side chain of arginine-136 in helix 4 of the Cry11A toxin.

• Journal of Korean Society of Environmental Engineers
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• v.34 no.2
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• pp.136-142
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• 2012

Various factors affecting on the bioassay were investigated. Experiments with a low mixture ratio (cell to toxicant solution) of 0.5 : 9.5 (v/v) produced observable bioluminescence intensity for assay. Both sodium lactate and potassium nitrate stimulate bioluminescence activity; 2.6~4.0 times of control. Distilled water and MSM, which gave non significant effects on the bioluminescence activity, were determined as proper diluent or extract solutions. A wide range of toxic responses of metals and organics were observed. In general, organics were much less sensitive than metals. Samples collected from eleven sites showed the bioluminescence activity ranging from 29 to 111% of the control. Significant correlation between toxicity and total metal contents was not observed, but the toxicity of two groups, sorted based on the contaminated arsenic concentration in soils, was 44% and 20%, showing considerable differences.