• Title/Summary/Keyword: Histopathological changes

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The Effect of Mineral-induced Alkaline Reduced Water on the DSS-induced Acute Inflammatory Bowel Disease Mouse Model (알칼리환원수 음용이 급성 염증성장질환 생쥐 모델에 미치는 영향)

  • Jin, Dan;Kim, Dong-Heui;Teng, Yung-Chien;Xufeng, Qi;Lee, Kyu-Jae
    • Applied Microscopy
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    • v.38 no.2
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    • pp.81-87
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    • 2008
  • Alkaline reduced water (ARW) has been used for drinking widely in several countries of Asia. The safety and clinical effects of ARW has been reported including anti-oxidative effect and intestinal abnormal fermentation. To confirm the effect of ARW on DSS-induced acute inflammatory bowel disease (IBD) mouse model, we observed the length of total large intestine and the histopathological changes after supplying mineral induced-ARW (MARW) for 2 weeks and oral administration of 4% DSS (dextran sulfate sodium). As the result, the length of total large intestine and the disease scores by macro and microscopical access in the ARWsupplied group showed no significant differences compared with those in the control group. This result suggests that the supply of ARW for 2 weeks exerted no effect on amelioration in the DSS-induced acute IBD model. However, in consideration of the effect of ARW on the improvement of intestinal environment and gastrointestinal disease, this result seems that acute IBD animal model is not suitable or the period of ARW supply is not enough to prove the effect of ARW. The ameliorative effect of ARW on the intestinal abnormal fermentation has been confirmed by some researchers, but the precise mechanism also remain unclear. In conclusion, although MARW had no effect on the DSS-induced acute experimental colitis model, further studies on the verification of the effects of ARW by using other intestinal disease model and by long-term supply of ARW will be required. Also, It needs to clear the mechanism of ARW on the intestinal environment.

Establishment of Quantitative Evaluation Method for Screening Testicular Toxicity in Rats: 2-Bromopropane as an Example (랫드에서 고환독성의 정색을 위한 정량적 평가법의 확립: 2-bromopropane의 예)

  • Cha Shin-Woo;Bae Joo-Hyun;Son Woo-Chan;Shin Jin-Young;Shin Dong-Ho;Kim Sung-Ho;Park Seung-Chun;Kim Jong-Choon
    • Journal of Life Science
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    • v.15 no.3 s.70
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    • pp.387-396
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    • 2005
  • The aims of the study were to establish a short-term screening test for detecting testicular toxicity of chemicals in rats and to determine whether a 2-week administration period is sufficient to detect testicular toxicity of 2-bromopropane (2-BP) as an example. Male Sprague-Dawley rats were subcutaneously administered with 1000 mg/kg/day of 2-BP or its vehicle for 2 weeks. Ten male rats each were sacrificed on days 3, 7 and 14 after the initiation of treatment. Parameters of testicular toxicity included genital organ weights, testicular sperm head counts, epididymal sperm counts, motility and morphology, and qualitative and quantitative histopathologic examinations. The early histopathological changes observed on day 3 of treatment included degeneration of spermatogonia and spermatocytes, multinuclear giant cells, mature spermatid retention, vacuolization of Sertoli cells, and decreased number of spermatogonia in stages II and V. On day 7 of treatment, atrophy of seminiferous tubules, exfoliation of germ cells, degeneration of spermatogonia and spermatocytes, multinuclear giant cells, mature spermatid retention, vacuolization of Sertoli cells, decreased number of spermatogonia in stages II and V, and decreased number of spermatocytes in stages VII and XII. On day 14 after treatment, a significant decrease in the weights of testes and seminal vesicles was found. Atrophy of seminiferous tubules, exfoliation of germ cells, degeneration of spermatogonia and spermatocytes, mature spermatid retention, vacuolization of Sertoli cells, decreased number of spermatogonia in stages II and V, and decreased number of spermatocytes in all spermatogenic stages were also observed. In addition, a slight non-significant decrease in testicular sperm head counts, daily sperm production rate and epididymal sperm counts was found. The results showed that 2 weeks of treatment is sufficient to detect the adverse effects of 2-BP on male reproductive organs. It is considered that the short-term testicular toxicity study established in this study can be a useful tool for screening the testicular toxic potential of new drug candidates in rats.

Studies on the Effect of Stress-Induced Gastric Ulcer on Gastric Carcinogenesis in Rats treated with N-methyl-N'-nitro-N-nitrosoguanidine (랫드에서 스트레스에 의한 위궤양이 위발암화과정에 미치는 영향에 관한 연구)

  • 이종권;김형진;이영순
    • Journal of Food Hygiene and Safety
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    • v.6 no.1
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    • pp.27-40
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    • 1991
  • ;ABSTRACT-The effects of gastric ulcer induced by restraint and water-immersion stress on gastric carcinogenesis in Wistar male rats treated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) were examined. Rats of group 1 were 2iven stress for 8 hours before they were received MNNG (100 mg/l) in drinking water for 20 weeks. Rats of group 2 were received MNNG first for 2 weeks and then were given stress once a week from 3rd to 12th weeks, with simultaneous MNNG adminitration and followed by MNNG only until 20th weeks. Rats of group 3 were received MNNG only as a positive control and rats of group 4 were not treated with carcinogen. All groups were sacrificed in 20 weeks. Sections of the pyloric mucosa were stained by avidin-biotin peroxidase complex (ABC) immuno-histochemical method. PAPG (pepsinogen isozyme 1 altered pyloric gland), body weight change, gross lesions and histopathological changes were examined. The results obtained from these studies were summarized as follows: 1. The mean body weight gains of the rats fed with carcinogens (group 1, 2, 3) were significantly lower than that of group 4 (control group, without carcinogen. p<0.05). However, the differences of the mean body weight of rats treated with carcinogen were not significant. 2. Stress treatment (group 1 and 2) increased the appearance of the numbers of PAPG (Pepsinogen 1 Altered Pyloric Gland) induced by carcinogen significantly compared with that of group 3 (carcinogen only, p<0.01). 3. The incidence rate of mucosal hyperplasia in pylorus was significantly increased in group 2 compared with group 3 (p<0.05).0.05).

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THE EFFECT OF HUMAN GROWTH HORMONE ON SEPSIS RAT MODEL INDUCED BY ENDOTOXIN (내독소(內毒素)에 의한 패혈증(敗血症) 백서(白鼠) 모델에서 성장(成長)호르몬 요법(療法)의 치료(治療) 효과(效果))

  • Ko, Kwang-Hee;Shin, Hyo-Keun
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.26 no.1
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    • pp.5-17
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    • 2000
  • To evaluate the possible therapeutic effects of growth hormone and vitamin C on multiorgan failure, a rat model was developed for LPS-induced sepsis. Using this model, the effects of growth hormone and vitamin C on tissue damages, catalase and i-NOS activities, and MDA levels were examined in the lung and liver. The level of TNF- in plasm was also examined. Male, Sprague-Dawley rats were injected with LPS intraperitoneally then divided into 3 groups : positive controls injected with LPS only, the ones injected with growth hormone or vitamin C immediately after the LPS injections. The lung and the liver were then isolated, blood samples were collected at 24 or 48 hours after the LPS injection, then examined for histopathological and biochemical changes. The results obtained were as follows. 1. LPS induced sinusoid vasodilation and mild destruction of lobular structure in the liver. In the lung, alveolar structure appeared to be thickened and interstitial edema was observed. The levels of MDA in the liver and the lung was increased by LPS, while the activity of catalase was decreased. The activity of i-NOS of those tissues was also increased, which was more pronounced at 24 hr. The level of TNF- in plasm was increased by LPS 2. In the lung, vitamin C suppressed lymphocyte and neutrophil infiltration, alveolar wall thickening and interstitial edema. In the liver, vitamin C protected against the destruction of the lobular structure. The activity of catalase reduced by LPS was reversed partly by vitamin C. The activity of i-NOS enhanced by LPS was also reversed by vitamin C. The level of TNF- in plasm reduced in some animals by vitamin C, which however was not significant statistically(p<0.05). 3. Growth hormone showed similar protective effects against inflammation and damages in the liver and lung tissues. Growth hormone reversed partly the LPS effects on the level of MDA, the activity of catalase and i-NOS induction in the liver and the lung. Growth hormone reduced plasma level of TNF-${\alpha}$ substantially, which contrasted from vitamin C. Besides this, overall protective effects of growth hormone against LPS-induced experimental sepsis were similar to those of vitamin C. From this results, the mechanism of growth hormone on suppression of LPS-induced tissue damage might be associated with production of antioxidative enzyme and suppression of plasma TNF- level.

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Protective Effect of Phosphatidylcholine on Lipopolysaccharide-Induced Acute Inflammation in Multiple Organ Injury

  • Jung, Yoon Yang;Nam, Yunsung;Park, Yong Seol;Lee, Ho Sung;Hong, Soon Auck;Kim, Beom Keun;Park, Eon Sub;Chung, Yoon Hee;Jeong, Ji Hoon
    • The Korean Journal of Physiology and Pharmacology
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    • v.17 no.3
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    • pp.209-216
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    • 2013
  • Soybean polyunsaturated phosphatidylcholine (PC) is thought to exert anti-inflammatory activities and has potent effects in attenuating acute renal failure and liver dysfunction. The aim of this study was to investigate the effects of PC in protecting multiple organ injury (MOI) from lipopolysaccharide (LPS). Six groups of rats (N=8) were used in this study. Three groups acted as controls and received only saline, hydrocortisone (HC, 6 mg/kg, i.v.) or PC (600 mg/kg, i.p.) without LPS (15 mg/kg, i.p.) injections. Other 3 groups, as the test groups, were administered saline, HC or PC in the presence of LPS. Six hours after the LPS injection, blood and organs (lung, liver and kidney) were collected from each group to measure inflammatory cytokines and perform histopathology and myeloperoxidase (MPO) assessment. Serum cytokines (TNF-${\alpha}$, IL-6 and IL-10) and MPO activities were significantly increased, and significant histopathological changes in the organs were observed by LPS challenge. These findings were significantly attenuated by PC or HC. The treatment with PC or HC resulted in a significant attenuation on the increase in serum levels of TNF-${\alpha}$ and IL-6, pro-inflammatory cytokines, while neither PC nor HC significantly attenuated serum levels of IL-10, anti-inflammatory cytokine. In the organs, the enhanced infiltration of neutrophils and expression of ED2 positive macrophage were attenuated by PC or HC. Inductions of MPO activity were also significantly attenuated by PC or HC. From the findings, we suggest that PC may be a functional material for its use as an anti-inflammatory agent.

The effect of artemisinin on the rabbit IgG accelerated nephrotoxic serum glomerulonephritis in mice (개똥쑥에서 분리(分離)된 artemisinin이 가토(家兎) IgG에 의해 유발(誘發)된 생쥐의 현독성(賢毒性) 혈청사구체현염(血淸絲球體賢炎)에 미치는 영향(影響))

  • Zhu, Quan
    • Journal of Haehwa Medicine
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    • v.4 no.2
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    • pp.335-336
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    • 1996
  • Artemisinin, a new antimalarial to treat patients infected with strains of Plasmodium jalciparum, derived from the plant Artemisia annua Linn, has immunopharmacologic actions such as enhence the PHA -induced lymphocyte transformation rate, increased the weight of spleen but reduced the weight of thymus, reduced phagocytic function of peritoneal macrophage, remarkably reduced the level of serum IgG and hemolysin fonning capacity (sentitized with SRBC), inhibited the activity of Ts cells of donor mice by supraoptimal immunuization(SOI), but enhenced activity of Ts cells of recipient mice by SOI. These results suggested that Ts cells may be the target cells of artemisinin. To the serum complement C3 level of plasmodium berghei-infeted mice, artemisinin (i. m,) could remarkly increase it. The artemisinin also obviously reduced the prostaglandin E(PGE) in the mouse hind paw swelling induced by carrageenin. Numerous studies have demonstrated that pharmacologic doses of PGE attenuate the development of immunocomplex nephritis. Some autologous immune mechanisms may be invoolved In the pathogensis of some types of glomurulonephritis. Glomerular abnormalities can be induced in animals by variety of immunological manipulations. The resulting disorder has many clinical and pathogical similarities to the disease in human. Our purpose was therefore to test the ability of the artemisinin to lessen the severity of rabbit IgG accelerated nephrotoxic serum glomerulonephritis in mice model. Mice which had treated with rabbit IgG and NTS, administrated with saline, showed Significant inceases of urinary protein, cholesterol level, and decrease of serum albumin in NS group. On the contrary, By i.g. adminstration of artemisinin at dose of 12.5, 25 and 50 mg/kg for 14 days after NTS injection, shown that artemisinin inhibited the nephritic changes in some parameters by means of urinary protein(p<0.05, p<0.01) and serum choleterol(p<0.05, p<0.01) and albumin (p<0.05, p<0.01), blood urea nitrogen (p<0.05, p<0.01), serum albumin(p<0.05, p<0.01); Cyclophosphamide(i.p. 10mg/kg for 14d) had almost same effect as the artemisinin had. Morphological studies shown that The picture of kidney from the mouse with NTS-nephritis accerated with rabbit IgG, treated with i.g. saline as the control, the mesangiocapillary were enlarged and proliferated; There were inflammatory cells infiltrating around the glomeruli; The ethelial cell were proliferated in the wall of Bowman's capsule. Histopatholological picture of kidney from the NTS-nephritis accerated with rabbit IgG mouse treated with i.p. 10mg/kg cyclophosphamide as the positive control. No siginicant histopathological evidence were found. Treaded with i.p. 12.5mg/kg artemisinine, the picture shown that mesangiocapillary were lightly proliferated; There were inflammatory cells infiltrating around the glomeruli; Treaded with i.p. 25mg/kg artemisinine, The picture shown that the mesangiocapillary were lightly proliferated; Treaded with i.p. 50mg/kg artemisinine, The picture shown that both the mesangiocapillary proliferated and the inflammatory cells infiltrating around the glomeruli are less than treated with saline, 12.5 and 25 mg/kg artemisinine. On the basis of these studies we conclude that the artemisinin can relieve pathological change caused by NTS-nephritis aacerated with rabbit IgG.

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A Potential Demerit of the Pronuclear Microinjection Technique (형질전환 마우스 생산 및 표현형에 pronuclear microinjection 이 미치는 영향 연구)

  • Wang, Ai-Guo;Kim, Sun-Uk;Moon, Hyung-Bae;Hyun, Byung-Hwa;Nam, Ki-Hoan;Suh, Jun-Gyo;Kim, Nam-Soon;Yu, Dae-Yeul;Lee, Dong-Seok
    • Journal of Life Science
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    • v.16 no.4
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    • pp.566-570
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    • 2006
  • Pronuclear microinjection (PMI) is a primary method for producing transgenic mice and offers a powerful tool for investigating gene function in vivo. The method has several reported advantages and disadvantages. Here, we report another potential shortcoming. The survival rate of fertilized one cell-stage embryos was significantly reduced after PMI procedure (65.4% (1202/1838)). In addition, the proportion of embryos developing to full-term was also significantly lower than that of embryos not undergoing PMI (26.5% (319/1202) vs 41.9% (57/136)). Moreover, 3 out of 21 (14.3%) founder control mice which were non-transgene-carrying littermates of transgenic founders showed histopathological changes in their liver, which was comparable to that in of transgenic lineages (4 out of 27 (14.8%)). In conclusion, the mechanical damages in chromosomes occurring during PMI procedure may be a potential factor influencing phenotypes of transgenic mice.

Pulmonary Toxicity Assessment of Aluminum Oxide Nanoparticles via Nasal Instillation Exposure (비강내 점적 노출을 통한 산화 알루미늄 나노입자의 폐독성 평가)

  • Kwon, Jung-Taek;Seo, Gyun-Baek;Lee, Mimi;Kim, Hyun-Mi;Shim, Ilseob;Jo, Eunhye;Kim, Pilje;Choi, Kyunghee
    • Journal of Environmental Health Sciences
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    • v.39 no.1
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    • pp.48-55
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    • 2013
  • Objective: The use of nanoparticle products is expected to present a potential harmful effect on consumers. Also, the lack of information regarding inhaled nanoparticles may pose a serious problem. In this study, we addressed this issue by studying pulmonary toxicity after nasal instillation of Al-NPs in SD rats. Methods: The animals were exposed to Al-NPs at 1 mg/kg body weight (low dose), 20 mg/kg body weight (medium dose) and 40 mg/kg body weight (high dose). To determine pulmonary toxicity, bronchoalveolar lavage (ts.AnBAL) fluid analysis and histopathological examination were conducted in rats. In addition, cell viability was investigated at 24 hours after the treatment with Al-NPs. Results: BAL fluid analysis showed that total cells (TC) count and total protein (TP) concentrations increased significantly in all treatment groups, approximately two to three times. Also, lactate dehydrogenase (LDH) and cytokines such as TNF-alpha and IL-6 dose-dependently increased following nasal instillation of Al-NPs. However, polymorphonuclear leukocytes (PMNs) levels showed no significant changes in a dose dependant manner in BAL fluid. In the cytotoxicity analysis, the treatment of Al-NPs significantly and dose-dependently induced cell viability loss (20 to 30%) and damage of cell membrane (5 to 10%) in rat normal lung epithelial cells (L2). Conclusions: Our results suggest that inhaled Al-NPs in the lungs may be removed quickly by alveolar macrophages with minimal inflammatory reaction, but Al-NPs have the potential to affect lung permeability. Therefore, extensive toxicity evaluations of Al-NPs are required prior to their practical application as consumer products.

Safety Evaluation of 30 kGy-Irradiated Dakgalbi (30 kGy 감마선 조사된 닭갈비의 안전성 평가)

  • Jeon, Young Eun;Yin, Xing Fu;Kim, Tae-Keun;Kang, Il-Jun
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.42 no.9
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    • pp.1475-1481
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    • 2013
  • The aim of this study was to determine the potential toxicity of gamma-irradiated Dakgalbi keeping in mind its future use as a space food. Dakgalbi was irradiated at a dose of 30 kGy at $-20^{\circ}C$. AIN-93G was used as a control diet in the animal study. Both irradiated and non-irradiated Dakgalbi diets were administered to two groups of ICR mice (ten male and ten female mice per group) for 3 months. During the experimental period, we observed that the mice fed the 30 kGy-irradiated Dakgalbi did not show any changes in appearance, behavior, mortality, body weight, organ weight, or food consumption compared to the control mice group. In addition, all biochemical parameters of these mice, including hematology profiles, erythrocyte counts, and serum biochemical values, remained in the normal range. The histopathological examinations of liver and kidney tissues showed no significant differences between the control group and the group fed the 30 kGy-irradiated Dakgalbi. These results indicate that Dakgalbi irradiated at 30 kGy did not cause any toxic effects in mice and therefore it can be considered as safe and hygienic space food.

Effects of J okyeongjongok-Tang on the Maturation of Follicles and NGF Expression in Rats with Estradiol Valerate-induced Polycystic Ovaries (조경종옥탕(調經種玉湯)이 Estradiol Valerate로 유발된 다낭성 난소 모델에서 난포의 성숙 및 NGF 발현에 미치는 영향(影響))

  • Yang, Joon-Mo;Seo, Il-Bock;Lee, Dong-Nyung;Kim, Hyung-Jun
    • The Journal of Korean Obstetrics and Gynecology
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    • v.24 no.2
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    • pp.52-67
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    • 2011
  • Objectives: This study was designed to investigate the effects of Jokyeongjongok -Tang(JJT) on the progression of the estradiol valerate(EV)-induced polycystic ovaries(PCO) in rats. Methods: PCO was induced by single intramuscular injection with estradiol valerate(EV)(4 mg) in female rats. Normal group(n=8) were injected with sesame oil and orally administrated distilled water for sixty days. PCO control group (n=8) were injected with EV and orally administrated distilled water for sixty days. JJT treated group(n=8) were injected with EV and orally administrated JJT for same duration. At the end day of experiment, we measured weights of body, ovaries, adrenal glands and uterus. The histopathological changes of ovaries were also evaluated. And we observed the NGF and CRF expression by immunohistochemistry. Results: The results were as follows - The weights(mg) of ovaries of JJT treated group($58.4{\pm}9.4$) were significantly increased(p<0.01) compared with PCO control group($42.3{\pm}8.5$). - The numbers of mature follicles of JJT treated group($10.1{\pm}2.5$) were significantly increased(p<0.01) compared with PCO control group($6.1{\pm}2.1$). - The numbers of cystic follicles of JJT treated group($1.8{\pm}1.4$) were significantly decreased(p<0.05) compared with PCO control group($3.8{\pm}1.5$). - The expressions of NGF-immunoreactive cells in the ovaries of JJT treated group were weaker than PCO control group. Conclusions: From the above results, we concluded that Jokyeongjongok-Tang (JJT) contributes to a normal maturation of follicles and has the effects of promoting a normal ovulation. And these effects may be related with the decreased NGF activities in the ovaries.