• Toxicological Research
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• 제23권4호
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• pp.391-403
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• 2007

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.

• 약학회지
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• 제51권1호
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• pp.1-6
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• 2007

The aim of this study was to examine whether administration of glutamine are able to prevent the methotrexate induced gut barrier damage, bacterial translocation, and weight changes. The animals with glutamine were fed with L-glutamine (1.2 and 2.4 mg/kg/day) for 7 days before methotrexate administration (20 mg/kg orally). 48 hour after methotrexate administration, intestinal permeability were measured for an assessment of the gut barrier dysfunction. Also, enteric aerobic bacterial counts, number of gram-negatives in mesenteric lymph node (MLN), liver spleen, kidney and heart were measured for an assessment of the enteric bacterial number and bacterial translocation. Amounts of food intake, body weight changes and organ weight changes of liver spleen, kidney and heart were measured. Methotrexate administration caused body and liver weight loss regardless amounts of food intakes. Methotrexate induced increasing intestinal permeability, enteric bacterial undergrowth and bacterial translocation to MLN, liver and spleen, but not kidney and heart. The supplements with glutamine reduced the intestinal permeability bacterial translocation, and not influences enteric bacterial number, and body and liver weight changes. This study suggested that glutamine might effectively reduce methotrexate induced intestinal damage and bacterial translocation, but not influence body and organ weight loss.

• 대한한방내과학회지
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• 제28권1호
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• pp.12-24
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• 2007

Objective : To investigate the effect of Samilshinkihwan(SISKW) on white rats with deteriorated immunity caused by methotrexate. Methods : The test articles were dosed once a day for 14 days by gastric gavage at a dosage 1000, 500 and 250mg/kg/10ml of SISKW from 2 days after last MTX-dosing, and changes in body weight, spleen weight, total blood leukocyte numbers, total lymphocyte numbers, B and T lymphocyte ratio, CD3+CD4+, CD3+/CD8+ and CD4+/CD8+ T lymphocyte ratio in the blood and spleen were measured. In addition, the serum interleukin (IL)-2 levels and the productivity of IL-2 of splenic cells were also demonstrated in this study. Results : The changes on body weight increased significantly in the 1000mg/kgof SISKW group. The changes on the spleen weight, the total blood leukocytenumbers, the total lymphocyte numbers in the blood and spleen, the ratio of T-cell in the blood and spleen and the ratio of CD3+CD4+ T-cell in spleen increased significantly in all SISKW groups as compared with the control group. The ratio of CD4+/CD8+ T-cells in blood increased significantly. The serum IL-2 levels and productivity of IL-2 of splenic cells increased significantly in 1000 and 500mg/kg SISKW groups as compared with the control group. Conclusions : Samilshinkihwanhas an effect of increasing immune responses, especially on cellular immune responses, in white rats with deteriorated immunity caused by methotrexate.

• 대한한방소아과학회지
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• 제12권1호
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• pp.211-230
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• 1998

Introduction The effects of Bojungikkitang on the immunosuppression induced by methotrexate in rats were investigated in this experiment. The multiple parameters of immunity assessed in. each rats includes the rate of body weight loss, weight changes in thymus, spleen and axillary lymphnode. The number of lymphocyte and CD4+ T cell count in blood, thymus, spleen and axillary lymphnode were also measured. Methodology Male Sprague-Dawley rats were chosen as an experiment object and were divided into 3 groups by a random selection. Each group consisted 6 rats. The normal group didn't receive any treatment. The control group was administered methotrexate for 4 days. The sample group was administered with both Bojungikkitang and methotrexate for 4 days. The dosage of medication was 2cc/day, 1cc given at 10AM and another 1cc given at 5PM. Results The rate of body weight loss was significantly decreased in the sample group. The weight of thymus was significantly increased in the sample group while the weight of spleen did not show much increase. Blood CD4+ T cell count, thymus lymphocyte count, thymus CD4+ T cell count, spleen lymphocyte count, spleen CD4+ T cell count and axillary lymph node CD4+ T cell count were significantly increased in the sample group while blood lymphocyte count and axillary lymphnode lymphocyte count did not show much increase. Conclusion As one can witness from the above results, administration of Bojungikkitang played potent role in increasing immune system among the rats treated with methotrexate which induces immunosuppression. Overall increase of lymphocyte count and CD4+ T cell count in the sample group with Bojungikkitang effectively proves its ability to boost the immune system.

• 대한한방소아과학회지
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• 제12권1호
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• pp.257-276
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• 1998

Introduction The effects of Samchulkunbitang on the immunosuppression induced by methotrexate in rats were investigated in this experument. The multiple parameters of immunity assessed in each rats includes the rate of body weight loss, weight changes in thymus, spleen and axillary lymphnode. The number of lymphocytes and CD4+ T cell count in the blood, thymus, spleen and axillary lymphnode were also measured. Methodology Male Sprague-Dawley rats were chosen as an experiment object and were divided into 4 groups by a random selection. Each group consisted of 6 rats. The normal group didn't receive any treatment. The control group was administered with methotrexate for 5 days. The sample Ⅰ group was administered with Samchulkunbitang for 5 days. The sample Ⅱ group was administered with both Samchulkunbitang and methotrexate for 5 days. The dosage of medication was 2cc/day, 1cc given at 10 AM and another 1cc given at 5 PM. Results The rate of body weight loss was significantly increased in the Sample Ⅰ and Sample Ⅱ group. The weight of thymus and spleen were significantly increased in Sample Ⅰ and Sample Ⅱ groups While the weight of axillary lymphnode did not show much increase. No significant differences were measured among the experimental groups. Blood lymphocyte count, blood CD4+ T cell count, spleen lymphocyte count, axillary lymphnode lymphocyte and CD4+ T cell count were significantly increased in Sample Ⅰ and Sample Ⅱ groups while spleen CD4+ T cell count did not show much increase. No significant differences were measured among the experimental groups. Conclusion As one can witness from the above results, administration of Samchulkunbitang played potent role in increasing immune system among the rats treated with methotrexate which induces immunosuppression. Overall increase of lymphocyte count and CD4+ T cell count in the sample groups with Samchulkunbitang effectively proves its ability to boost the immune system.

• Applied Microscopy
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• 제28권4호
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• pp.551-561
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• 1998

The autometallographic method was used to demonstrate the localization of mercury deposits in spleen of mouse. The mercury deposits were identified with the light and electron mocroscope. Mice were treated with methylmercuric chloride in the drinking water (demineralized water) for 40 days. Control and mercury treated groups showed no significant differences in mean body weight and spleen weight per one mouse. Mercury grains were appeared in the germinal center of white pulp consist of a preponderancing lymphocytes, not in red pulp and capsule. At the ultrastructural level, mercury deposits were restricted to lysosomes of macrophage and lymphocyte. Specially, volume in lysosomes of the macrophage was increased. These results suggest that mercury localization in lysosomes is associated with the change of immune activity.

• Environmental Analysis Health and Toxicology
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• 제1권1호
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• pp.27-36
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• 1986

Experiments were performed on mice to investigate the effect of Panax ginseng petroleum ether fraction on the immunotoxicity of lead acetate. Lead acetate was administered in the drinking water and ginseng p-ether fraction was injected intraperitoneally, Mice were sensitized and challenged with sheep red blood cell. Humoral immune responses were evaluated by antibody production and Arthus reaction. Pathotoxicological influences were measured by serum protein, alkaline phosphatase and total cholesterol. The weight of liver, spleen and thymus were measured. Lead acetate exposure significantly decreased hemagglutination titer, hemolysin titer, Arthus reaction, spleen and thymus weight. Ginseng p-ether fraction administration significantly restored or potentiated reduced humoral immune response, spleen and thymus weight. Reduced serum A/G ratio, total cholesterol and alkaline phosphatase activity were restored or increased by ginseng p-ether fraction administration.

• Journal of Microbiology and Biotechnology
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• 제31권5호
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• pp.726-732
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• 2021

In this study, we evaluated the immune-enhancing activity of kimchi-derived Lactobacillus plantarum 200655 on immune suppression by cyclophosphamide (CP) in ICR mice. Animals were fed distilled water or 1×10⁹ colony-forming unit/kg B.W. 200655 or Lactobacillus rhamnosus GG as a positive control for 14 days. An in vivo model of immunosuppression was induced using CP 150 and 100 mg/kg B.W. at 7 and 10 days, respectively. Body weight, spleen index, spleen weight, and gene expression were measured to estimate the immune-enhancing effects. The dead 200655 (D-200655) group showed an increased spleen weight compared to the sham control (SC) group. Similarly, the spleen index was significantly higher than that in the CP-treated group. The live 200655 (L-200655) group showed an increased mRNA expression of tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6 in splenocytes. Also, the iNOS and COX-2 mRNA expression was upregulated in the L-200655 group compared to the CP-only (SC) group. The phosphorylation of ERK and MAPK was also upmodulated in the L-200655 group. These results indicate that L. plantarum 200655 ameliorated CP-induced immune suppression, suggesting that L. plantarum 200655 may have the potential to enhance the immune system.

• Environmental Analysis Health and Toxicology
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• 제22권2호통권57호
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• pp.147-156
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• 2007

Six week-old ICR mice were divided into four groups including NC, RC, RR and RS, then they were injected with sun ginseng (RS), red ginseng (RR) and saline (RC) intraperitoneally as an amount of 60mg/kg body weight at 1 hour, 12 hours and 36 hours before the whole body irradiation with 6.5Gy of X-ray. And the mice were sacrificed at nine days after the irradiation. The RS group were significant increase in the weight of spleen (p<0.05) and the numbers of endogenous spleen colony (p<0.001) and WBC (p<0.05) especially neutrophils, lymphocytes and monocytes in comparison with the RC group. The RR group were significant increase in the numbers of endogenous spleen colony (p<0.01) and WBC (p<0.05) especially neutrophils, lymphocytes and eosinophils in comparison with the RC group. The RS group exhibited a more increase in the weight of spleen and the number of endogenous spleen colony than the RR group. The values of ALT (alanine transaminase) and AST (aspartate transaminase) were significantly elevated (p<0.05) by radiation and they were significantly decreased (p<0.05) in the RS group to the values of the NC group. The value of TBARS(thiobarbituric acid reactive substance) was significantly elevated (p<0.01) by radiation and it was significantly decreased (p<0.05) in the RS group. And the values of SOD (superoxide dismutase) and CAT (catalase) were significantly increased (p<0.05) in the RS group in comparison with the RC group. Taken together the above results, sun ginseng demonstrated the protective effects on hepatocytes and immune and hematopoietic cells in mice exposed to medium dose of irradiation, and those radioprotective effects were a little higher or similar to the red ginseng.

• 사상체질의학회지
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• 제35권1호
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• pp.14-24
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• 2023

Objectives This study was conducted to observe physiological changes when the function of spleen was extremely deteriorated, and to make an animal model with spleen deficiency. Methods The Normal group (Nr group) was not administered with Senna Folium extract. The SFE group(Senna Folium extract group) was administered with Senna Folium extract every day for the first 2 weeks and then every other day for another week. And the SFE_G group(Senna Folium extract_Ginseng group) was also administered with Senna Folium for 3weeks like the SFE group and fed with ginseng in the third week. Results The score of spleen deficiency was significantly higher in SFE group than in the Nr group and significantly lower in the SFE_G group than in the SFE group. The total weight gain was significantly lower in the SFE group than in the Nr group, and the average daily weight gain was significantly lower in the SFE group than in the Nr group. The difference in stool weight before and after the process of drying was significantly higher in the SFE group than in the Nr group, and significantly lower in the SFE-G group than the SFE group. There was no significant difference in the outcomes related to cold and heat among the three groups. Conclusions Through this study, the animal model with spleen deficiency was developed to prepare a stepping stone for animal tests to verify the efficacy and safety of constitutional prescriptions.