• Korean Journal of Environmental Agriculture
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• v.33 no.2
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• pp.103-110
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• 2014

BACKGROUND: Azadirachta indica has been widely used as environment-friendly organic materials because of its insecticidal properties. This study was carried out to investigate the acute toxicity and the subacute toxicity of Azadirachta indica extract(AIE) in rats. METHODS AND RESULTS: For the oral acute toxicity test, Sprague-Dawley rats were gavaged with 2.0 g/Kg bw of AIE. The $LD_{50}$ value was greater than 2.0 g/Kg bw for both male and female rats. For the subacute toxicity study, rats were treated with AIE at doses of 0.5, 1.0, 2.0 mg/Kg bw once a day for 4 weeks(n=10 animals per each group). There were no significant changes in body weight, food intake and water consumption observed during the experimental duration. In addition, no difference of relative kidney weight was observed among all treated groups. Serum creatinine level in the AIE 2.0 g/Kg group increased significantly compared with that of control group in male rats, but serum blood urea nitrogen was significantly decreased in a dose-dependent manner (p<0.05). Significant increase of serum cholesterol levels were observed in all AIE groups, compared with the control group, in the female rats (p<0.05). However, histopathological examination of the kidney did not reveal any significant lesions in all groups. CONCLUSION: On the basis of results, it could be concluded that oral administration AIE didn't cause any toxic response in kidney, except the increased serum cholesterol.

• Environmental Analysis Health and Toxicology
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• v.8 no.1_2
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• pp.37-58
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• 1993

In order to investigate the toxicities of S-bioallethrin (5-biol) and its combination treatment with N-octyl bicycloheptene dicarboximide (MGK-264), the acute and subacute toxicity, and enzyme activity test were performed. $LD_{50}$ levels of S-biol and MGK-264 in rats are 640 mg/kg and 3, 280 mg/kg respectively. However, when rats were treated with the mixture of S-biol and MGK-264 (1 : 5 ratio), the $LD_{50}$ was decreased to 545 mg/kg. In serological analysis, ALT and LDH were increased in animals treated with the mixture. Also glucose level was significantly increased after 5 weeks in animals treated with both S-biol and the mixture. Other biochemical parameters such as cytochrome P-450 and NADPH-cytochrome c reductase in the liver and kidney were shown to be not significantly changed. Levels of total ATPase and $mg^{2+}$ ATPase were significantly decreased in the liver of animals treated with the mixture after 4-5 weeks. In addition, S-biol can alone decrease total ATPase activity. Total ATPase activity was also significantly decreased in the kidney after 5 week treatment with the mixture. Similarily, glucose-6-phosphatase activity was significantly decreased in animals treated with the mixture. When either S-biol or MGK-264 was administered, cholinesterase and carboxyesterase activities were slightly decreased but they were significantly decreased when the mixture was administered.

• Journal of the Korean Society of Food Science and Nutrition
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• v.20 no.1
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• pp.13-20
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• 1991

For this experiment frist the fermented Soybean Meju was prepared by domestic ordinary method of Korean and concentrated Meju suspensoidal extract was made for toxicological test sample on mice and rat. Even the oral dose of 10g extract per kg of mice had not any acute toxicity. So the median lethal dose(LOD50) is lilely to be much greatr or not to be. In comparison of the average weight gain rate for 4 weeks the control and test groups of 0.308g Ex/rat kg and 9.24g Ex/rat kg daily were the much the same as about 19% but 3.08g Ex/rat kg group waas exceptionally 2.7% higher than control For this period all test groups did not show any abnormality in appearance and anatomic findings. In serum GPT GOT alkaline phosphatase and blood urea nitrogen value there were no difference significantly between control and the test groups of 0.308g/rat kg and 3.08g/rat kg but 9.24g/rat kg group was some what higher than control. Especially in cholesterol alkaline phosphatase and blood urea nitrogen value 9.24g/rat kg group or 28days had 100mg/이 37.5u 32mg/이 respectively which were increased significantly. The pathological findings of all test groups especially 9.24g/kg group did not showed any characterized sign of acute or subacute liver damage or intestine lesion. So it is supposed that there is not any tocixants originated from some molds in fermented Korean domestic Meju which is prepared traditionally in winter.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.04a
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• pp.248-248
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• 1996

경구투여급성독성시험 : 암수동물의 모든 투여군에서 시험물질투여에 의한 일반증상, 체중변화 및 육안적 부검소견은 관찰되지 않았으며. 따라서 반수치사량(LD$_{50}$)은 암수동물의 경우 5000mg/kg이상이었다. 경구투여아급성독성시험 : SD랫트의 암수 동물에 있어서 Captopril(SR Tablet 25mg)의 2000mg/kg 용량은 확실중독량에 해당되며, 무영향량(NOEL)은 220mg/kg용량이라고 사료되었다.

• Food Science of Animal Resources
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• v.25 no.4
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• pp.465-471
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• 2005

This study was carried out to evaluate the effectiveness of anti-Helicobacter pylori IgY powder to suppress infection of Helicobacter pylori in humans. Hens were immunized with H. pylori to produce a specific anti-H. pylori IgY in their egg yolks, and then anti-H. pylori IgY Powder was used a sample after egg yolks were harvested The safety tests of anti-H. pylori IgY powder were conducted a acute and subacute toxicity test, The result was that the mice fed IgY powder were normal state on a acute and subacute toxicity test The effect of anti-H. pylori IgY powder was evaluated by urease breath test, Volunteers who tested positive for H. pylori using a $^{13}C-urea$ breath test were divided in two groups, one was administrated with anti-H. pylori IgY powder (11.2g/day) and natural extract mixture and the other was administrated with water soluble protein fraction (3.2g/day) of anti-H. pylori IgY powder, The results of clinical test in two groups were shown reduction of UBT value about 23 and 18 respectively. This result indicates that anit-H. pylori IgY is safety and can be used toy the effective supplement as an ingredient of functional food.

• Advances in Traditional Medicine
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• v.7 no.4
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• pp.395-408
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• 2007

This study reports the analgesic, anti-inflammatory and membrane-stabilizing property of alcoholic extract of Ophiorrhiza nicobarica (ON), a wild herb, used as an anti-infective ethnomedicine of Nicobarese and Shompen tribes of Great Nicobar Island, India. We for the first time investigated the analgesic and antiinflammatory potential of this herb in acute, subacute and chronic model of inflammation in Swiss albino mice and Wistar albino rats, along with sheep RBC-induced sensitivity and membrane stabilization. The acetic acid induced writhing, tail flick and tail immersion tests are used as a model for evaluating analgesic activity; while the carrageenin-induced paw oedema was used as the model for acute inflammation, dextran-induced oedema as sub-acute and cotton-pellateinduced granuloma as chronic inflammatory model. The probable mode by which ON mediate its effect on inflammatory conditions was studied on sheep RBC-induced sensitivity and membrane stabilization. The in vitro results revealed that the ON extract possesses significant (P < 0.05) dose dependent analgesic and antiinflammatory activity at 200 and 300 mg/kg and its fractions at 50 mg/kg, p.o. respectively, compared to the control groups. However, the extract failed to exhibit membrane-stabilizing property as it unable to reduce the level of haemolysis of RBC exposed to hypotonic solution. The acute toxicity studies of ON extract in rats and mice revealed that the extract was nontoxic even up to 3.0 g/kg body weight of the animals, with a high safety profile. We have isolated ursolic acid, ${\beta}$-sitosterol and harmaline respectively, from the bioactive part of the extract. The results indicated that the O. nicobarica is indeed beneficial in primary health care, and suggest that its anti-inflammatory activity may not be related to membrane-stabilization.

• Environmental Analysis Health and Toxicology
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• v.20 no.3 s.50
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• pp.243-248
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• 2005

Mancozeb (MCZ), a polymeric complex of zinr and manganese salts of ethylene bisthiocarbamate, is widely used in agriculture as fungicidel, insecticides, and herbicides. MCZ can be occupationally and environmentally exposed to human and has been reported to have detrimental effects on the reproductive system, but the toxicity of MCZ on immune responses has not been systematically investigated. We investigated the effects of MCZ exposure on the activities of murine splenocytes through evaluation of splenocytes cellularity and INF-$\gamma$ synthesis. Splenocytes were examned ex vivo from mice orally treated with various doEes of MCZ for 1 day (acute exposure, 2,100, 5,000, 10,000 mg/kg) or ior 5 consecutive days per week for 4 weeks (subacute exposure,250, 1,000, 1,500 mg/kg/day) fellowed by culture for 2 days in the presence of Con A or PHA plus IL-2. Splenocytes Iron naive mice were cultured with various concentration of MCZ (50, 500, 1,000 ng/ml) in the presence of Con A or PHA plus IL-2 for 2 days in vitro. IFN-$\gamma$ production was decreased with the in vitro exposure to all concentration of MCZ. The spleen cellularity and IFN -$\gamma$ production by splenocytes from MCZ -acutely and - subacutely exposured mice were decreased in comparision with that oi control group.

• Korean Journal of Pharmacognosy
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• v.20 no.3
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• pp.180-187
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• 1989

Systematic pharmacological studies on powdered whole part of unossified antler obtained from Cervus nippon Temminck var. mantchuricus have been carried out in mice and rats. Powdered antler, with a single oral administration, showed a very weak acute and subacute toxicity; its MLD being >5g/kg orally in mice. On daily oral treatments of the antler for 14 days, it did not cause any significant differences in body weight gain, various organ weights and serum transaminase activities compared to those of the control rats. Powdered antler, with a single oral administration, showed a remarkable analgesic activity as evaluated by writhing syndrome and tail-pressure test, a weak CNS depressant activity as well as a weak immunopotentiating action as evaluated by carbon clearance test in mice. Powdered antler, with repeated treatments, showed a moderate antifatigue effect against immobilized stress and showed significant increases in both adrenal weight and its ascorbic acid content in rats, suggesting that the mode of antifatigue effect of antler is related to adrenal and its components.

• Korean Journal of Environmental Agriculture
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• v.7 no.1
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• pp.58-64
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• 1988

The acute oral, intraperitoneal and subacute toxicity of monocrotophos, an insecticide, was studied in albino rats. The acute oral $LD_{50}$ values for female and male rats were 5.0mg/kg and 8.7mg/kg, respectively. Conversely the intraperitoneal $LD_{50}$ values for female and male rats were 4.9mg/kg and 6.0mg/kg, respectively. Plasma cholinesterase (ChE) activity in rats treated with a single dose was the most depressed 4 hours after administration, but returned to normal within 72 hours of administration. Significant depression of body weight gain and food consumption was observed in rats receiving the 3.5mg/kg/day dose level for 28 days as compared with the controls. Additionally plasma ChE activity depression was also observed.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4597-4606
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• 2012

Cholangiocarcinoma (CCA) is an uncommon adenocarcinoma which arises from the epithelial cells of the bile ducts. The aim of the study was to investigate the cytotoxicity, toxicity, and anticancer activity of a crude ethanolic extract of ginger (Zingiber officinale Roscoe) against CCA. Cytotoxic activity against a CCA cell line (CL-6) was assessed by calcein-AM and Hoechst 33342 assays and anti-oxidant activity was evaluated using the DPPH assay. Investigation of apoptotic activity was performed by DNA fragmentation assay and induction of genes that may be involved in the resistance of CCA to anticancer drugs (MDR1, MRP1, MRP2, and MRP3) was examined by real-time PCR. To investigate anti-CCA activity in vivo, a total of 80 OV and nitrosamine (OV/DMN)-induced CCA hamsters were fed with the ginger extract at doses of 1000, 3000, and 5000 mg/kg body weight daily or every alternate day for 30 days. Control groups consisting of 10 hamsters for each group were fed with 5-fluorouracil (positive control) or distilled water (untreated control). Median $IC_{50}$ (concentration that inhibits cell growth by 50%) values for cytotoxicity and anti-oxidant activities of the crude ethanolic extract of ginger were 10.95, 53.15, and $27.86{\mu}g/ml$, respectively. More than ten DNA fragments were visualized and up to 7-9 fold up-regulation of MDR1 and MRP3 genes was observed following exposure to the ethanolic extract of ginger. Acute and subacute toxicity tests indicated absence of any significant toxicity at the maximum dose of 5,000 mg/kg body weight given by intragastric gavage. The survival time and survival rate of the CCA-bearing hamsters were significantly prolonged compared to the control group (median of 54 vs 17 weeks). Results from these in vitro and in vivo studies thus indicate promising anticancer activity of the crude ethanolic extract of ginger against CCA with the absence of any significant toxicity. Moreover, MDR1 and MRP3 may be involved in conferring resistance of CCA to the ginger extract.