• Title/Summary/Keyword: Cd-induced hepatotoxicity

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Effect of Mungbean Sprouts Juice on Cadmium-Induced Hepatotoxicity in Rats (녹두나물 생즙이 카드뮴에 의한 흰쥐의 간손상에 미치는 영향)

  • 이명렬;최인화;김성오;김경수
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.27 no.5
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    • pp.980-986
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    • 1998
  • The effects of mungbean sprout juice on cadmium-induced hepatotoxicity in rats were investigated. Sprague-Dawley rats weighing about 90g were divided into 4 groups and raised for 6 weeks. ; control group(CON), mungbean sprouts juice-administered group(MSJ), cadmium-administered group(CAD) fed water containing 40 ppm cadmium chloride and mung bean sprouts juice and cadmium-administered group(MCD). The diet was supplied every day for the measurement of feed efficiency ratio(FER) and net weight gain was measured every 3 days. The activities of serum glutamic oxaloactic transaminase(GOT) and glutamic pyruvic transaminase(GPT), superoxide dimutase(SOD), catalase and glutathione peroxidase(GSH-Px) in the liver and the hepatic contents of glutathione were examined. The contents of Cd in liver and kidney of the rats were determined by using ICP(Inductively Coupled Plasma Emission Spectrophotometer). Growth rate and FER were decreased in CAD group, compared with CON group but the changes were not significant in MCD group. The activities of serum GOT and GPT, SOD, catalase and GSH-Px in the liver were increased by Cd administration, but the alterations were decreased by supplementation with mungbean sprouts juice. The level of glutathione decreased in CAD group(26.8$\pm$9.0mg/g liver), whereas it increased in MCD group(36.4$\pm$15.8mg gliver). The content of Cd in the liver and kidney in MCD group(9.57 ppm, 4.88 ppm) was decreased, compared with CAD group(12.81 ppm, 5.46 ppm). This result suggested that mungbean sprout juice has a lowering effect on the accumulation of Cd in the liver and kidney and it is believed that the juice has some protective effects to Cd-induced hepatotoxicity in rats, but the mechanism of these effects was obscure.

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Analysis of Gene Expression in 4,4'-Methylenedianiline-induced Acute Hepatotoxicity

  • Oh, Jung-Hwa;Yoon, Hea-Jin;Lim, Jung-Sun;Park, Han-Jin;Cho, Jae-Woo;Kwon, Myung-Sang;Yoon, Seok-Joo
    • Toxicological Research
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    • v.25 no.2
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    • pp.85-92
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    • 2009
  • 4,4'-Methylenedianiline (MDA) is an aromatic amine that is widely used in the industrial synthetic process. Genotoxic MDA forms DNA adducts in the liver and is known to induce liver damage in human and rats. To elucidate the molecular mechanisms associated with MDA-induced hepatotoxicity, we have identified genes differentially expressed by microarray approach. BALB/c male mice were treated once daily with MDA (20 mg/kg) up to 7 days via intraperitoneal injection (i.p.) and hepatic damages were revealed by histopathological observation and elevation of serum marker enzymes such as AST, ALT, ALP, cholesterol, DBIL, and TBIL. Microarray analysis showed that 952 genes were differentially expressed in the liver of MDA-treated mice and their biological functions and canonical pathways were further analyzed using Ingenuity Pathways Analysis (IPA). Toxicological functional analysis showed that genes related to hepatotoxicity such hyperplasia/hyperproliferation (Timp1), necrosis/cell death (Cd14, Mt1f, Timp1, and Pmaip1), hemorrhaging (Mt1f), cholestasis (Akr1c3, Hpx, and Slc10a2), and inflammation (Cd14 and Hpx) were differentially expressed in MDA-treated group. This gene expression profiling should be useful for elucidating the genetic events associated with aromatic amine-induced hepatotoxicity and for discovering the potential biomarkers for hepatotoxicity.

Inhibitory Effects of Gwanjul9-bang on Collagen Induced Arthritis in DBA/1J Mouse (관절9호방이 생쥐의 Collagen II 유발 관절염에 미치는 영향)

  • Kim, Eun-Hye;Oh, Min-Seok
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.24 no.3
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    • pp.490-503
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    • 2010
  • This study was carried out to know the effects of Gwanjul9-bang (hereinafter reffered to GJ9) on the inhibition of arthritis induced by collagen on DBA/1J mouse. For this purpose, GJ9 was orally administered to mouse with arthritis induced by collagen II. Cytotoxicity, hepatotoxicity, arthritis index, value of immunocyte in draining lymph node and paw joint, rheumatoid factor (IgG, IgM) in serum were measured in vivo. The cytotoxicity against hFCs was not measured in any concentration. The hepatotoxicity was low in GJ9 treated group compared with MTX group. The arthritis index was decreased significantly. In total cell counts of DLN and paw joint, the cells in DLN increased significantly while there was significantly decrease in paw joint. In lymph nodes, $CD19^+$, $CD3^+$, $CD4^+$, $CD3^+CD69^+$, $CD8^+$, $CD4^+CD25^+$, $CD3^+CD49b^+$, $CD4^+CD44^+$, $CD3^+CD8^+$ cells increased significantly, $B220^+CD23^+$cells decreased significantly. In joints, $CD3^+$, $CD4^+$, $CD4^+CD25^+$, $CD11b^+Gr-1^+$ cells decreased significantly. The levels of IgG and IgM was significantly decreased compared with control. Anti-collagen II in serum was significantly decreased compared with control. The degree of arthritis induced damage of joint of GJ9 group is slight compared with control group in histopathologic observation (Hematoxylin & Eosin, Masson's Trichrome). Comparison of the results for this study showed that GJ9 had immunomodulatory effects. So we expect that GJ9 should be used as a effective drugs for not only rheumatoid arthritis but also another auto-immune disease. Therefore we have to survey continuously in looking for the effective substance and mechanism in the future.

Suppressive Effect of GJB-7 on Collagen-Induced Arthritis in Mice (관절7호방이 Type II collagen으로 유발된 흰쥐의 관절염에 미치는 영향)

  • Min, Boo-Ki;Oh, Min-Seok
    • The Journal of Korean Medicine
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    • v.31 no.4
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    • pp.63-78
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    • 2010
  • Objectives: This study was carried out to know the effects of Gwan-Jul-Bang-7 (hereafter referred to GJB-7) on the inhibition of arthritis induced by collagen on the mouse. Methods: To assess the effects of GJB-7 on mouse with arthritis induced by collagen II, we conducted several experiments such as analysis of cytotoxicity, hepatotoxicity, arthritis index, total cell number of draining lymph nodes and paw joints, value of immunocyte in PBMC (peripheral blood mononuclear cell), DLN (draining lymph node) and paw joint, measurement of cytokine and anti-collagen II, observation of the histological changes of joint. Results: 1. Cytotoxicity against HFC (human fibroblast cells) was not observed in any concentration and hepatotoxicity was not observed in the GJB-7 treated group. 2. The incidence of arthritis significantly decreased. 3. Total cell number of draining lymph nodes significantly increased and total cell number of paw joints significantly decreased. 4. The percentage of $CD8^+$ cells in PBMC (peripheral blood mononuclear cell) significantly increased. The percentage of $CD3^+/CD69^+$, and $CD3^+/CD49b^+$ cells in PBMC significantly decreased. 5. The percentage of $CD19^+,\;CD3^+$, and $CD4^+/CD25^+$ cells in DLN (draining lymph nodes) significantly increased. The percentage of $B220^+/CD23^+$ cells in DLN significantly decreased. 6. The percentage of $CD3^+,\;CD4^+$, and $CD11b^+/Gr-1^+$ cells in paw joints significantly decreased. 7. The production of TNF-$\alpha$, IL-6, and MCP-1 significantly decreased. 8. Anti-collagen II in serum significantly decreased. 9. With the hematoxylin and eosin stain, inflammation of joint decreased. Under Masson's trichrome stain, the cartilage destruction and synovial cell proliferation and the expression of collagen fibers decreased. Conclusions: Comparison of the results for this study showed that GJB-7 had immunomodulatory effects. So we expect that GJB-7 could be used as an effective drug for not only rheumatoid arthritis but also another auto-immune diseases.

Inhibitory Effects of Changchuldoin-tanggamibang on Collagen Induced Arthritis in DBA/1J Mouse (창출도인탕가미방(蒼朮桃仁湯加味方)이 DBA/1J 생쥐의 collagen 유발 관절염 억제에 미치는 영향)

  • Park, Jang-Woo;Oh, Min-Seok
    • The Journal of Korean Medicine
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    • v.31 no.2
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    • pp.19-35
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    • 2010
  • Objectives: This study was carried out to find the effects of Changchuldoin-tanggamibang (hereinafter referred to CDIT) on the inhibition of arthritis induced by collagen on DBA/1J mouse. Methods: The experimental mice were divided into four groups: normal group (Nr), control group (CIA-CT), methotrexate group (CIA-MTX), and Changchuldoin-tanggamibang group (CIA-CDIT). Cytotoxicity, hepatotoxicity, arthritis index, value of immunocytes in draining lymph node and paw joint, and rheumatoid factor (IgG, IgM) in serum were measured in vivo. Results: 1. Cytotoxicity against hFCs was not shown in any concentration. 2. Hepatotoxicity was low in the CDIT-treated group compared with the MTX group. 3. The arthritis index decreased significantly. 4. In total cell counts of DLN and paw joint, the cells in DLN increased significantly while there was a significant decrease in paw joint. 5. In lymph nodes, CD19+, CD3+, CD4+, CD8+, CD3+/CD8+, CD3+/CD69+, CD4+/CD25+, CD3+/CD49b+, and CD4+/CD44+ cells increased significantly, while B220+/CD23+, and CD11c+/MHCII+ cells decreased significantly. 6. In joints, CD3+, CD4+, CD4+/CD25+, and CD11b+/Gr-1+ cells decreased significantly. 7. The level of IgG decreased and the level of IgM significantly decreased compared with the control. 8. Anti-collagen II in serum decreased compared with the control. 9. Around the joint of the CDIT group, infiltration of inflammation, synovial hyperplasia, invasion of cytokine, of cartilage, deposition of collagen and synovial injury decreased compared with the control in histopathologic observation (HE, MT staining). Conclusions: Comparison of the results for this study showed that CDIT had immunomodulatory effects. We expect that CDIT could be used as a effective drug for not only rheumatoid arthritis but also another auto-immune diseases. Therefore, we have to survey continuously, looking for effective substances and mechanisms in the future.

Effect of Pine Needle Water Extract on Cadmium-Induced Oxidative Stress in Rats (솔잎 열수추출물이 카드뮴으로 유도한 흰쥐의 산화적 손상에 미치는 영향)

  • Jang, Joo-Yeun;Kim, Myung-Joo;Lee, Mi-Kyung;Kim, Duk-Jin
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.36 no.4
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    • pp.411-418
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    • 2007
  • Oxidative stress can play a key role in cadmium (Cd)-induced dysfunction. The present study examined the effect of pine needle water extract (PN) on Cd-induced oxidative stress in rats. Sprague-Dawley male rats were divided into three groups: normal group, Cd control group (Cd) and PN-administered Cd group (Cd-PN). $CdCl_2$ in 0.9% NaCl was administered orally with a dose of 5mg/kg of body weight/week, while the PN was administered orally with a dose of 1.26g/kg of body weight/day. Body weight gain was not different between groups, whereas food intakes were significantly lower in the Cd-PN group than in normal or Cd group. Relative liver weight was significantly increased by cadmium administration compared to the normal group. Hepatic cytochrome P450 was significantly lower in Cd and Cd-PN groups than in normal group, while xanthine oxidase and alcohol dehydrogenase activities were significantly higher in the Cd-PN group than in normal or Cd group. Increased hepatic superoxide dismutase, monoamine oxidase, catalase, and glutathione peroxidase activities by cadmium administration were significantly decreased by PN supplement. PN did not affect the hepatic glutathione content in cadmium-administered rats; however, PN significantly lowered the hepatic lipid peroxide level and plasma alanine transferase activity compared to the Cd control group. These results suggest that the PN may alleviate Cd-induced oxidative stress without hepatotoxicity.

Oral Exposure to Mercury Alters T Lymphocyte Phenotypes and Augments LPS-induced Cytokine Expressions in Spleen and Thymus (비장과 흉선의 림프세포와 LPS에 의해 유도된 사이토카인의 발현에 대한 수은의 영향)

  • 김상현;최철희;임종필;신태용
    • YAKHAK HOEJI
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    • v.48 no.4
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    • pp.241-246
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    • 2004
  • Mercury is a widespread metal and consequently there are large populations that currently exposed to low levels of mercury. Endotoxin is a component of the gram-negative bacteria and promotes inflammatory responses. The present study was designed to determine the impact of mercury on lymphocytes phenotype populations and endotoxin-induced inflammatory cytokine expressions in immune organ, spleen and thymus. Male BALB/c mice were exposed continuously to 0, 0.3, 1.5, 7.5, or 37.5 ppm of mercuric chloride in drinking water for 14 days and at the end of the treatment period, lipopolysaccharide (LPS, 0.5 mg/kg) was injected intraperitoneally 2 h prior to euthanasia. The dose-range of mercury used did not cause hepatotoxicity. Mercury at 7.5 and 37.5 ppm dose-dependently decreased CD3$^{+}$ T lymphocytes in spleen; both CD4$^{+}$ and CD8$^{+}$ single positive lymphocyte populations were decreased. Exposure to 7.5 and 37.5 ppm of mercury decreased the CD8$^{+}$ T lymphocyte population in the thymus, whereas double positive CD4$^{+}$ / CD8$^{+}$ and CD4$^{+}$ thymocytes were not altered. Mercury altered LPS-induced inflammatory cytokine gene expressions such as, tumor necrosis factor $\alpha$, interferon ${\gamma}$, and interleukin-12 in spleen and thymus. Results indicated that decreases in T lymphocyte populations in immune organs and altered cytokine gene expression may contribute to the immune-modulative effects of inorganic mercury.ganic mercury.

Effect of Dietary Zinc Levels on Cadmium-Induced Hepatotoxicity in Rats (식이성 아연 수준이 카드뮴 중독에 미치는 영향)

  • 조수열;김명주
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.23 no.4
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    • pp.574-580
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    • 1994
  • The effect of dietary zinc(Zn) levels on cadmium (Cd)-induced hepatotoxicity was studied in serum and liver of rats. Adult male Spraque-Dawley rats were fed on diets containing one of three levels of zinc carbonate(0, 56, $560\mu\textrm{g}/kg$ diet) and Cd-treated groups were administrated oral intubation with cadmium chloride 95.0 mg/kg of body weight) at the sametime once a week. Net weight gain (NWG), feed intake (FI) and feed effciiency ratio (FER) in Zn deficiency groups significantly decreased as compared to that of control and excessive groups. Cd oral intubation caused a decrease in NWG and FI but an increase in Zn deficiency group in FER. GSH-Px, GST and catalase activity showed significant decrease in Zn deficiency and Zn excessive group. LPO content in liver significantly increased in Zn deficiency group. Cd oral intubation increased the content of LPO in Zn deficiency group as compared to control. GSH content and GST activity of hepatic tissue significantly decreased in Zn deficiency and excessive group. The activity of AST and ALT in serum were markedly increased in Zn deficiency, Zn excessive and Cd-treated groups. LDH and ALP activities significantly increased in Cd-treated group while ALP activity decreased by Zn deficiency. It was observed that the livers of rats exposed to Cd and Zn excessive group showed a marked increase of hepatic enzyme as compare to only Cd-treated in rats.

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Effects of Gwanjul8-bang on Collagen Induced Arthritis in DBA/1J Mice (관절8호방이 Collagen 유발 관절염에서 DBA/1J 생쥐에 미치는 영향)

  • Kim, Jong-Kook;Oh, Min-Seok
    • Journal of Korean Medicine Rehabilitation
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    • v.20 no.2
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    • pp.17-34
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    • 2010
  • Objectives : This study was carried out to know the effects of Gwanjul8-bang(here in after reffered to GJ8) on the inhibition of arthritis induced by collagen on DBA/1J mice. Methods : For this purpose, GJ8 was orally administered to mouse with arthritis induced by collagen II. Cytotoxicity, hepatotoxicity, arthritis index, value of immunocyte in draining lymph node(DLN) and paw joint, cytokine in serum were measured in vivo. Results : 1. The arthritis index was decreased significantly. 2. In total cell counts of DLN and paw joint, the cells in DLN increased significantly while there was a significant decrease in paw joint. 3. In lymph nodes, $CD19^+$, $CD3^+$, $CD4^+/CD25^+$ cells increased significantly, and $B220^+/CD23^+$ cells decreased significantly. 4. In joints, $CD3^+$, $CD4^+$, $CD11b^+/Gr-1^+$ cells decreased significantly. 5. The levels of $TNF-{\alpha}$, IL-6, IL-17, MCP-1 and vascular endothelial growth factor(VEGF) in serum was significantly decreased compared with control. 6. Anti-collagen II in serum was significantly decreased compared with control. 7. The degree of arthritis induced damage of joint of GJ8 group is slight compared with control group in histopathologic observation(hematoxylin & eosin(H&E), Masson-Trichrome(MT) staining). Conclusions : Comparison of the results for this study showed that GJ8 had immunomodulatory effects. So we expect that GJ8 should be used as a effective drugs for not only rheumatoid arthritis but also another auto-immune disease. Therefore there seems to be many clinical research needed in the future.

Effects of GP extract on oxidative stress and contact dermatitis in NC/Nga Mice induced by DNCB (가감평위산(加減平胃散)이 산화적 손상과 접촉성 피부염에서의 면역 조절작용에 미치는 영향)

  • Park, Eung-Ho;Yun, Mi-Young;Kim, Seon-Bin;Kim, Dong-Hee
    • Journal of Haehwa Medicine
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    • v.16 no.2
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    • pp.131-145
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    • 2007
  • To evaluate the effects of GP on contact dermatitis, we examined the composition of immune cells from drain lymph node in DNCB-induced contact dermatitis murine model NC/Nga mice. And the amount of pathologic cytokines of spleen and antioxidant activity were investigated. The results were summarized as followers; 1. GP did not show cytotoxic effect on mLFC in vitro. 2. GP did not have hepatotoxicity in vivo in the level of ALT, AST. 3. GP decreased the production of DPPH and in a dose-dependent. 4. GP significantly decreased total cell number of DLN in DNCB-induced NC/Nga mice compared to the untreated control group. 5. GP significantly decreased the number of CD3+, CD19+, CD4+, CD8+, CD3+/CD69+ and CD4+/CD45+ in DLN of DNCB-induced NC/Nga mice compared to the untreated control group. 6. GP significantly reduced the level of IL-4 and IFN-$\gamma$ in splenocytes of DNCB-induced NC/Nga mice compared to the untreated control group. Taken together above results, GP have therapeutic effects on contact dermatitis by regulating T cell activation. This study warranted further investigations of molecular mechanisms of GP on contact dermatitis.

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