• Title/Summary/Keyword: Histopathological findings

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Single and Four-Week Repeated Oral Toxicity Study of Antidiabetic Herb Extract Microcapsule in Sprague-Dawley Rats (항당뇨 한약추출고형물의 Sprague-Dawley 랫드를 이용한 단회 및 4주 반복투여 독성시험)

  • Kim, Young-Chul;Kim, Hye-Jeong;Kong, Min-Kyu;Lim, Ae-Kyoung;Kwon, Mi-Hwa;Kim, Kil-Soo;Lee, Gee-Dong
    • Toxicological Research
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    • v.23 no.1
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    • pp.87-96
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    • 2007
  • Single and repeated-dose toxicity of anti-diabetic herb extract microcapsule (ADHEM) were evaluated according to Toxicity Test Guidelines of Korea Food and Drug Administration using Sprague-Dawley rats. For single-dose toxicity test, kneading ADHEM with sterilized water were administered orally once at dose levels of 0 and 2,000 mg/kg and examined for 14 days. No dead animals, clinical signs and abnormal necropsy findings were observed and also no significant difference in body weights was found. Therefore, the $LD_{50}$ of ADHEM was considered to be higher than 2,000 mg/kg in both male and female rats. For repeated-dose toxicity test, ADHEM were mixed with powder fodder and administerd orally for 28 days at dose levels of 0, 500, 1000 and 2000 mg/kg/day. No dead animals, clinical signs and significant difference in body weights were found. In hematology and serum biochemistry, all values were included within the normal ranges. In relative organ weights, kidney or liver were significantly increased in the 500, 1000 or 2000 mg/kg/day male groups, uterus was significantly increased in the 500 mg/kg/day female group and left adrenal glands were significantly decreased in the 2000 mg/kg/day female group. In histopathological examinations, vacuolation and microgranuloma in the liver, chronic progressive nephropathy and inflammation in the kidney were observed in the 500, 1000 or 2000 mg/kg/day both male and female groups. Therefore, the no observed adverse effect level (NOAEL) of ADHEM was considered to be lower than 500 mg/kg/day in both male and female rats.

Single Oral Dose Toxicity Study of Prebrewed Armeniacae Semen in Rats

  • Park, Ji-Ha;Seo, Bu-Il;Cho, Su-Yeon;Park, Kyu-Ryul;Choi, Seung-Hoon;Han, Chang-Kyun;Song, Chang-Hyun;Park, Soo-Jin;Ku, Sae-Kwang
    • Toxicological Research
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    • v.29 no.2
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    • pp.91-98
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    • 2013
  • Armeniacae semen (AS) has been considered a toxic herb in the Korean medicine as it contains hydrogen cyanide and amygdalin, especially in its endocarp. Therefore, prebrewed AS that is devoid of endocarp has been traditionally used. In the present study, amygdalin content of the prebrewed AS was significantly lower ($2.73{\pm}0.32{\mu}g/ml$; p<0.01) than the content in the extract that contained the endocarps ($28.50{\pm}6.71{\mu}g/ml$); amygdalin content corresponded to 10% of the extract in the present study. Because of single oral dose toxicity of prebrewed AS according to the recommendation of Korea Food and Drug Administration Guidelines (2009-116, 2009), which was based on single oral dose toxicity study of prebrewed AS, mortality due to toxic principles was significantly reduced. In this study, 2,000 mg/kg of prebrewed AS led to death of 1 female rat and 1 male rat at the end of 2 hr of administration. Based on these results, the 50% lethal dose in both male and female rats was determined to be 9279.5 mg/kg. Seizure, loss of locomotion, and increases in respiration and heart rate were observed as prebrewed AS treatment-related toxicological signs; these signs were restrictedly manifested in the prebrewed AS (2,000 mg/kg)-treated rats. In addition, no changes were observed in body weight, organ weight, gross features, and histopathological parameters with 2,000 mg/kg of AS in both male and female rats. These findings serve as direct evidence that amygdalin in AS is the toxic principle, which can be reduced by the traditional prebrewing method involving the exclusion of endocarp.

Modulation of Inflammatory Cytokines and Islet Morphology as Therapeutic Mechanisms of Basella alba in Streptozotocin-Induced Diabetic Rats

  • Arokoyo, Dennis S.;Oyeyipo, Ibukun P.;Du Plessis, Stefan S.;Chegou, Novel N.;Aboua, Yapo G.
    • Toxicological Research
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    • v.34 no.4
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    • pp.325-332
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    • 2018
  • The mechanism of the previously reported antidiabetic effect of Basella alba is unknown. This study investigated the role of B. alba aqueous leaf extract in the modulation of inflammatory cytokines and islet morphology in streptozotocin-induced diabetic rats. Forty male Wistar rats, between 8 and 10 weeks old, were randomly divided into four groups (n = 10) and administered the following treatments: Healthy control (H-c) and Diabetic control (D-c) animals received normal saline 0.5 mL/100 g body weight daily, while Healthy Treatment (H-Ba) and Diabetic Treatment (D-Ba) rats received the plant extract 200 mg/kg body weight daily. All treatments were administered by oral gavage. Diabetes was induced in D-c and D-Ba rats by a single intraperitoneal injection of streptozotocin (55 mg/kg body). The body weight and fasting blood sugar (FBS) levels were recorded every week for 4 weeks, after which the rats were euthanized and samples collected for further analysis. After the experiment, FBS level was significantly reduced (p < 0.0001) in rats in the D-Ba group, but increased (p < 0.001) in rats in the D-c group. The absolute (H-c and H-Ba vs D-c, p < 0.05) and relative (D-Ba vs H-c, p < 0.05; D-Ba vs H-Ba, p < 0.005) weights of the pancreases were significantly higher after the experiment. The rats in the D-c group had significantly higher levels of serum interleukin-$1{\beta}$ (p < 0.001 vs H-c; p < 0.05 vs H-Ba and D-Ba) and monocyte chemotactic protein-1 (p < 0.0001), but lower levels of interleukin-10 (p < 0.05) in comparison with the other groups. Histopathological examination revealed severe interstitial congestion, reduced islet area (p < 0.0001), and increased islet cell density in the D-c group compared with those in the D-Ba group. From these findings, it was concluded that the aqueous extract of B. alba stimulates the recovery of beta-islet morphology in streptozotocininduced diabetic rats by modulating the peripheral production of inflammatory cytokines.

Effect of Toluene or Ethanol Pretreatment on Toluene Metabolism in Rats (렛트에 톨루엔 및 에탄올 전처치가 톨루엔 대사에 미치는 영향)

  • Cha, Sang-Eun;Jeon, Tae-Won;Yoon, Chong-Guk
    • Journal of Korean Society of Occupational and Environmental Hygiene
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    • v.8 no.2
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    • pp.296-305
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    • 1998
  • A study was performed to evaluate an effect of toluene or ethanol pretreatment on the toluene metabolism. A slight liver damage in rats was induced by administration of 0.2 ml of toluene or 0.2 ml of 50% ethanol per 100 g of body weight intraperitoneally every other day for four weeks except the last day before sacrifice. One day before sacrifice, toluene was administered to rats pretreated ethanol or toluene and the control. Rats were sacrificed at the 1st, the 2nd, the 3rd and the 4th week after the first administration of xenobiotics mentioned above. Based on the histopathological findings, liver weight per body weight, serum alanine aminotransferase and hepatic glutathione content, toluene- or ethanol-pretreated groups showed the reversible liver injury. By the treatment of one dose of toluene, the contents of hippuric acid in urine was higher in the group pretreated with toluene or ethanol than control. The contents of cytochrome P-450, benzylalcohol dehydrogenase and benzaldehyde dehydrogenase activities were generally more increased in toluene- or ethanol-pretreated rats than control. $K_m$ values of the benzylalcohol dehydrogenase in pooled liver samples from toluene- and ethanol-pretreated groups were similar each other. $V_{max}$ values of toluene- or ethanol-pretreated group was higher than control. In conclusion, the toluene metabolism is accelerated in rats pretreated with toluene or ethanol.

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A Case of Subacute Necrotizing Lymphadenitis Presenting as Fever of Unknown Origin (불명열로 오인된 아급성 괴사성 림프선염 1례)

  • Yang, In Suk;Park, Kyung Ho;Kang, Jin Han;Kim, So Young;Lee, Won Bae;Kim, Hyun Hee
    • Pediatric Infection and Vaccine
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    • v.8 no.2
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    • pp.253-259
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    • 2001
  • Kikuchi's disease(histiocytic necrotizing lymphadenitis) is characterized by lymphadenopathy in young patients below 30 years old, and persistent fever, lymphopenia and splenomegaly are concomitantly developed in many cases. So, it has been confused with lymphoma, SLE, and tuberculosis, and has easily led to inappropriate diagnostic procedures and administration of drugs. Many reports have indicated that Kikuchi's disease should be added to the list of causes of FUO in the setting of lymphadenopathy, and recommended early lymph node biopsy to distinguish from lymphoma, SLE, and tuberculosis to avoid unnecessary treatments. We experienced a case of subacute necrotizing lymphadenitis in a 14-year-old boy who presented with persistent high fever, productive coughing and cervical lymphadenopathy for about 1 month. Initially, diagnostic workup was done to look for the causes of FUO in vain. Finally, we confirmed diagnosis by histopathological findings of lymph node biopsy and detected latent gene of EBV in the biopsied specimen using in situ hybridization.

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Diagnosis and Management of Lymphoplasmacytic Rhinitis in a Cat (림포형질세포성 비염에 이환된 고양이의 진단과 치료)

  • Kang, Min-Hee;Park, Hee-Myung
    • Journal of Veterinary Clinics
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    • v.28 no.4
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    • pp.438-441
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    • 2011
  • A 7-year-old castrated, domestic shorthair cat was presented with a 2-year history of chronic nasal discharge and sneezing. Upon presentation, bilateral mucopurulent nasal discharge and stertorous respiration were marked. Physical examination revealed a tachypnea. Oral examination was unremarkable and chest radiology was normal. Findings of nasal cytology and skull radiology were not specific and further imaging technique, endoscopic examination and histopathology was performed for a definite diagnosis. Fluid, and/or soft tissue opacity was found in bilateral nasal cavity, nasopharyngeal regions and right side tympanic bulla through the CT scan. No evidence of neoplasia was revealed. A rigid rhinoscopy, flexible bronchoscopy and otoscopy was used for the visualization of the lesions and tissue biopsy biopsy was performed for histopathology. On histopathological examination, the nasal mass consisted mainly of large numbers of plasma cells and lymphocytes. And the final diagnosis was lymphoplasmacytic rhinitis based on histopathologic examination. Long term management with oral cyclosporine (5 mg/kg, BID) was safe and successful in this cat. This is the first case report described clinical and diagnostic characteristic features of feline lymphoplasmacytic rhinitis and its clinical outcome using oral cyclosporine in Korea.

Severe Focal Cystic Endometrial Hyperplasia in a Bitch (개에서 발생한 국소성 거대 낭상자궁내막증식증 1예)

  • Lee, Jae-Yeon;Shin, Beom-Jun;Park, Ji-Young;Lee, Young-Won;Park, Seong-Jun;Cho, Sung-Whan;Kim, Myung-Cheol;Jeong, Seong-Mok
    • Journal of Veterinary Clinics
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    • v.28 no.6
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    • pp.610-612
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    • 2011
  • A 9-years-old female Collie dog was presented with history of abdominal enlargement, anorexia and constipation. On radiographic and ultrasonographic examinations, intra-abdominal mass was identified. On cytologic findings of the mass, no cancer cell was observed. Exploratory laparotomy was performed to diagnose and remove the mass. A large, single, spheroid mass weighing 9.5 kg ($40{\times}25{\times}18$ cm) was located in the middle section of the right uterine horn. Based on the results of histopathological examination, the mass was diagnosed as a cystic endometrial hyperplasia (CEH). This is rare case of severe focal CEH without pyometra in a bitch.

In vivo Acute Toxicity of Silicon Dioxide Nanoparticle to Mice after Intraperitonial Injection (이산화규소 나노입자의 마우스 복강 내 주입에 의한 급성독성)

  • Cha, Chun-Nam;Jung, Won-Chul;Lee, Yeo-Eun;Yoo, Chang-Yeul;Kim, Gon-Sup;Kim, Eui-Kyung;Kim, Suk;Lee, Hu-Jang
    • Journal of Food Hygiene and Safety
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    • v.26 no.1
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    • pp.43-48
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    • 2011
  • For the application of nano-sized material in various fields, the evaluation of nano-sized material toxicity is important. In the present study, various concentrations of 200 nm-sized silicon dioxide nanoparticle suspension were intraperitonially injected into mice to identify the toxicity of silicon dioxide nanoparticle in vivo. In the hematological analysis of group II treated with silicon dioxide nanoparticle 100 mg/kg body weight, lymphocytes and monocytes were significantly different compared to the control group. In group III treated with silicon dioxide nanoparticle 200 mg/kg body weight, lymphocytes, monocytes and hemoglobin were significantly different compared to the control group. In blood biochemical analysis of group III, the concentration of AST, ALT, BUN, and creatinine were significantly different compared to the control group. Histopathologic examination of the kidney indicated a mild injury only in mice received 200 mg/kg silicon dioxide nanoparticle. According to the results of the present study, the significant differences in the hematological and blood biochemical analyses and abnormal histopathological findings in the mouse kidney may have been related to exposure to silicon dioxide nanoparticle.

28-Day Oral Toxicity of Cadmium Selenide in Sprague-Dawley Rats

  • Kim, Yong-Soon;Song, Moon-Yong;Kim, Jin-Sik;Rha, Dae-Sik;Jeon, Yong-Joon;Kim, Ji-Eun;Ryu, Hyeon-Yeol;Yu, Il-Je;Song, Kyung-Seuk
    • Toxicological Research
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    • v.25 no.3
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    • pp.140-146
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    • 2009
  • This study was performed to evaluate the toxicity of cadmium selenide for a period of 28 days in Sprague-Dawley rats. Each of 10 healthy male and females rats per group received daily oral administration for 28-day period at dosage levels 30, 300 and 1,000 mg/kg of body weight. Mortality and clinical signs were checked, and body weight, water intake and food consumption were also recorded weekly. There were no dose-related changes in food consumption or urine volume. All animals survived to the end of study with no clinical signs or differences in body weight gain observed when compared with the control group. At the end of study, all animals including control group, were subjected to necropsy. Blood samples were collected for hematology tests including coagulation time and biochemistry analysis. Blood coagulation time and relative organ weight were unaffected by all received doses. White Blood Cell (WBC) counts significantly increased in the 300 mg/kg administered male animal group when compared to the control. Monocyte (MO) value were also increased significantly in both 300 and 1,000 mg/kg male animal group. However, Mean Corpuscular Volume (MCV) were significantly decreased compared with the control in the 1,000 mg/kg dose groups for male and female animals. Mean Corpuscular Hemoglobin (MCH) decreased significantly for female in the 300 and 1,000 mg/kg group compared to the control. Blood biochemical values of Inorganic phosphorus (IP) were significantly increased in both the 300 and 1,000 mg/kg dose groups in male animals when compared to the control. Creatinine (CRE) levels indicated significant increase in kidney function for the female, 30 mg/kg dose group when compared with control. There was a significant decrease in thymus absolute organ weight in the female, 1,000 mg/kg dose group when compared with control. Histopathological findings revealed no evidence of injury related to cadmium selenide except for one case of focal hepatic inflammation in the high dose (1,000 mg/kg) group. One case of lung inflammation was also seen in the control group. Basis on these result, the No Observable Adverse Effect Level (NOAEL) of cadmium selenide was determined to be more than 1,000 mg/kg/day for male and female rats under conditions in this study.

Mouse Single Oral Dose Toxicity Test of Chongmyung-tang Aqueous Extracts (총명탕(聰明湯) 열수(熱水) 추출물의 마우스 단회 경구투여 독성 실험)

  • Hwang, Ha-Yeon;Jang, Woo-Seok;Baek, Kyung-Min
    • The Journal of Internal Korean Medicine
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    • v.35 no.1
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    • pp.37-49
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    • 2014
  • Objectives & Methods : The objective of this study was to evaluate the single oral dose toxicity of Chongmyung-tang (CMT) in ICR mice. Korean traditional herbal prescription CMT has traditionally been used as a neuroprotective for treatment of learning disability and memory improvement. CMT, lyophilized aqueous extracts (yield=9.7%) were administered to female and male mice with oral dose of 2,000, 1,000 and 500 mg/kg (body weight) according to the recommendation of Korea Food and Drug Administration (KFDA) Guidelines. Animals were monitored for mortality, changes in body weight, clinical signs and gross observation during 14 days after administration upon necropsy; organ weight and histopathology of 14 principle organs were examined. Results : We could not find any CMT extracts treatment related mortalities, clinical signs, changes in body and organ weight, or gross and histopathological observations against 14 principle organs up to 2,000 mg/kg in both female and male mice, except for some accidental sporadic findings which did not show any obvious dose-relations and most of which also demonstrated in both the female and male vehicle control mice in this experiments. Conclusions : Based on the results of this experiment, the 50% lethal dose ($LD_{50}$) and approximate lethal dose (ALD) of CMT extracts after single oral treatment in female and male mice can be considered to be over 2,000 mg/kg, and is likely to be safe in humans.