• 대한수의학회지
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• 제23권1호
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• pp.57-67
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• 1983

The present study was carried out to observe the histopathological changes in the mammary gland of lactating rats and rabbits injected with dexamethasone. White rats were intramuscularly injected with 0.25mg, 0.5mg or 1.0mg of dexamethasone sodium phosphate (containing $9{\alpha}$-fluoro-$16{\alpha}$-methylprednisolone, 5.0mg/ml) daily for 3 to 10 days on the 3rd day after parturition and white rabbits were intramammary infused with 4mg or 20mg of dexamethasone daily for 4 days on 7th day after parturition. The histopathological changes of the mammary glands, ovaries and adrenal glands of rats and rabbits were observed with light microscope. In the mammary glands of rats, the microscopic findings encountered were decrease of the milk in the alveolar lumina, necrosis and desquamation of epithelial cells, atrophy of alveoli, proliferation of fibroblasts and thickness of alveolar walls, destruction of alveoli, presence of fat droplets within the glandular epithelial cells, infiltration of mononuclear cells and proliferation of adipose tissue, which were relative to the dose and duration of injection. Especially, in the cases of the administration of large doses or long duration, there were severe fibrosis and focal necrosis of glandular tissue. In the mammary glands of rabbits, the morphological changes were similar to those findings in the rats. The milk in the alveolar lumina was decreased gradually according to the dose and duration of injection, while milk fat concentration regarded to increase. In the histological findings of ovaries, necrosis of granulosa cellos, vacuolization and necrosis of luteal cells, atrophy and necrotic foci in the corpora lutes were observed. In the adrenal glands, hyperemia, hemorrhage, vacuolization of adrenal cortical cells, necrotic foci and atrophy of adrenal cortex were observed.

• Applied Microscopy
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• 제32권4호
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• pp.399-410
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• 2002

죽력의 투여에 따른 생쥐 간세포의 항산화효소 활성변화와 간과 신장의 조직병리학적 변화에 미치는 영향을 통하여 치료약물로써 죽력의 안전성 확보에 기여하고자 본 연구를 수행하였다. 대조군은 생리식염수를 투여하였으며, 실험군은 죽력을 생리식염수에 5% (H1군), 10% (H2군), 20% (H3군)로 희석하여 0.2 ml씩 48시간 간격으로 28일 동안 구강 투여하였다. 대조군과 실험군의 간조직을 절취하여 SOD와 catalase의 활성변화를 측정하였으며, 간과 신장의 조직학적변화 및 미세구조적 변화를 관찰하였다. MnSOD의 활성은 대조군에 비하여 H1 (46%, P<0.05), H2 (40%, P<0.05), H3군 (34%, P<0.05)에서 증가하였다 (Fig. 1). CuZnSOD의 활성은 대조군에 비하여 H1군 (11%, P<0.05)에서는 증가하였으나, H3군 (13%, P<0.05)에서는 감소하였다. Catalase의 활성은 대조군에 비하여 H1 (39%, P<0.05), H2 (34%, P<0.05), H3군 (31%, P<0.05)에서 감소하였다. 간과 신장의 조직병리학적 관찰 결과, H3군에서 간세포의 팽창과 중심정맥 내피세포의 파괴현상이 뚜렷이 나타났으며, 신장의 곱슬세관 상피세포의 파괴현상이 뚜렷하였다. H2군의 간세포는 핵질이 매우 응축되어 있었으며, 사립체의 팽대현상이 현저하였다. H3군은 핵질의 전자밀도가 매우 낮게 나타났다. 사립체의 내강은 매우 팽대되어 있고 크리스테의 형태는 관찰되지 않으면서 기질의 전자밀도는 낮게 나타났다. H3군 근위곱슬소관의 원주상피세포는 핵의 괴사가 뚜렷하였으며, 세포질내에서 관찰되는 사립체들은 대부분 팽대되거나 파괴된 양상을 보여주었다. 이상의 연구 결과로 보아 죽력은 투여 농도에 따라 간세포의 항산화효소 활성의 변화와 간과 신장의 조직 병리학적 변화를 초래한다고 생각된다.

• 한국어병학회지
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• 제24권3호
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• pp.225-236
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• 2011

본 연구에서는 조피볼락의 간의 육안적 색조에 따른 병리조직학적 소견 및 혈액학적 소견에 근거하여 건강상태를 확인하였다. 조피볼락 총 47개체 모두 외부 소견에서는 특기할 이상 소견이 없었으나, 간은 육안적으로 정상간 (42.55%), 황간 (25.53%), 갈변 위축간 (25.53%), 녹간 (4.26%) 및 지방간 (2.13%) 순으로 나타났다. 간의 육안적 소견에 따른 조피볼락의 간의 조직 소견 관찰시, 정상 간 개체는 HE 염색 시 간세포가 밝게 염색되며, 소엽구조가 불명확하게 관찰되었으나, 황간 개체는 황갈색의 과립이 간세포 및 MMC 내에 관찰되었으며, 간세포는 정상 간 개체에 비해 크기가 위축되어 세포질이 짙은 호산성으로 관찰되며, 세포질 내에 핵과 유사한 크기의 황갈색 초자적이 한 개 이상 관찰되었다. 한편, 녹간 개체는 정상 간 개체에 비해 간세포 크기가 위축으로 관찰되며, HE 염색 시 황갈색과 녹색의 초자적이 간세포 및 MMC 내에 관찰되었으며, 담즙색소 동정을 위한 Stein 염색에서 간세포질 내에서 담즙색소로 추정되는 녹색의 초자적이 관찰되었다. 갈변 위축 간 개체는 간세포의 용적이 줄어들어, 중심정맥 및 동양 모세혈관의 이완이 확인되었다. 그리고 갈변 위축 간이 육안적으로 갈색으로 관찰되나 광학현미경적 관찰결과 간세포질 내에 색소과립은 관찰되지 않았으며, 간세포의 경계가 명확하게 나타나지 않았다. 지방간 개체는 지방 소적의 축적으로 간세포에 다양한 크기의 둥근 지방 공포가 광범위하게 관찰되었으며, 지방소적으로 인해서 팽창된 간세포가 관찰되거나, 간세포핵의 변성이 관찰되었다. 본 연구 결과, 간의 육안적 관찰 및 조직학적 관찰 결과가 어체의 임상 질병으로 실질적인 발현을 진행하기 전에 중요한 건강 매개변수로 사용될 수 있을 것으로 판단되었다.

• 대한한의학방제학회지
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• 제16권1호
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• pp.147-168
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• 2008

HYTE (Hyeonggaeyeongyotang Extract), a polyherbal formula has been used as folk medicine, 28days repeat oral dose toxicity was tested in SD rats according to KFDA Guideline[2005-60]. Methods : In this study, mortality, clinical signs, body weight and gains, food and water consumption, ophthalmologic observation, urinalysis, hematology, serum biochemistry, gross findings, organ weight and histopathological observations were conducted during 28days of dosing periods. Results: 1. No HYTE treatment-related mortalities and clinical signs were detected in all dosing levels tested in male and female rats during the whole experimental periods. 2. No HYTE treatment-related changes on body weight, gains and food consumption were detected in all dosing levels tested in male and female rats during the whole experimental periods except for 2000mg/kg-dosing female groups in which significantly increase of body weight, gains, food and water consumption were detected compared to that of vehicle control in some points. 3. No HYTE treatment-related changes on ophthalmologic examination were detected in all dosing levels tested in male and female rats. 4. No HYTE treatment-related changes on urinalysis were detected in all dosing levels tested in male and female rats except for 2000mg/kg-dosing female groups in which, significantly increase of urine volume and related decrease on the urine specific gravity were detected as secondary effects of increase on the water consumptions not HYTE treatment-related toxicological signs. 5. No HYTE treatment-related changes on hematology were detected in all dosing levels tested in male and female rats except for increases in the total WBC count and lymphocytes of 2000mg/kg-dosing male and female groups with decrease of large unstained cells as pharmacological effects of immune enhancements not HYTE treatment-related toxicological signs. 6. No HYTE treatment-related changes on serum biochemistry were detected in all dosing levels tested in male and female rats. 7. No HYTE treatment-related changes on gross findings, organ weight and histopathology were detected in all dosing levels tested in male and female rats except for 2000mg/kg-dosing male and female groups in which, spleen and thymus organ weights, hypertrophy at gross observation and hyperpalsia of lymphoid cells and follicles at histopathological observation in spleen and thymus were detected as pharmacological effects of immune enhancements not HYTE treatment-related toxicological signs. Conclusions : Based on these results, the NOAEL and MTD of HYTE in SD rats were considered as over 2000mg/kg, respectively at 28days repeat oral dose toxicity test because most of these findings were considered as results of pharmacological effects of immune enhancements not HYTE treatment-related toxicological signs or secondary effects.

• Biomolecules & Therapeutics
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• 제23권6호
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• pp.597-603
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• 2015

Synthetic cannabinoids JWH-018 and JWH-250 in 'herbal incense' also called 'spice' were first introduced in many countries. Numerous synthetic cannabinoids with similar chemical structures emerged simultaneously and suddenly. Currently there are not sufficient data on their adverse effects including neurotoxicity. There are only anecdotal reports that suggest their toxicity. In the present study, we evaluated the neurotoxicity of two synthetic cannabinoids (JWH-081 and JWH-210) through observation of various behavioral changes and analysis of histopathological changes using experimental mice with various doses (0.1, 1, 5 mg/kg). In functional observation battery (FOB) test, animals treated with 5 mg/kg of JWH-081 or JWH-210 showed traction and tremor. Their locomotor activities and rotarod retention time were significantly (p<0.05) decreased. However, no significant change was observed in learning or memory function. In histopathological analysis, neural cells of the animals treated with the high dose (5 mg/kg) of JWH-081 or JWH-210 showed distorted nuclei and nucleus membranes in the core shell of nucleus accumbens, suggesting neurotoxicity. Our results suggest that JWH-081 and JWH-210 may be neurotoxic substances through changing neuronal cell damages, especially in the core shell part of nucleus accumbens. To confirm our findings, further studies are needed in the future.

• 동의생리병리학회지
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• 제24권1호
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• pp.134-142
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• 2010

Although BinSo-San(BSS), a mixed herbal formula consisted of 11 types of medicinal herbs and have been used as anti-inflammatory agent, In the present study, the acute toxicity (single oral dose toxicity) of lyophilized BSS aqueous extracts was monitored in male and female mice after oral administration according to Korea Food and Drug Administration (KFDA) Guidelines (2005-60, 2005). In order to observe the 50% lethal dose ($LD_{50}$), approximate lethal dosage (ALD), maximum tolerance dosage (MTD) and target organs, test articles were once orally administered to female and male ICR mice at dose levels of 2000, 1000, 500, 250 and 0 (control) mg/kg (body wt.) according to the recommendation of KFDA Guidelines (2005-60, 2005). The mortality and changes on body weight, clinical signs and gross observation were monitored during 14 days after dosing according to KFDA Guidelines (2005-60, 2005) with organ weight and histopathology of 12 types of principle organs. We could not find any mortality, clinical signs and changes in the body weights except for dose-independent increases of body weight and gains restricted in 1000 mg/kg of BSS extracts-dosing female group. Hypertrophic changes of lymphoid organs.thymus, spleen and popliteal lymph nodes were detectedat postmortem observation with BSS extracts dose-dependent increases of lymphoid organ weights, and hyperplasia of lymphoid cells in these all three lymphoid organs at histopathological observations. These changes are considered as results of pharmacological effects of BSS extracts or their components, immunomodulating effects, not toxicological signs. In addition, some sporadic accidental findings such as congestion spots, cyst formation in kidney, atrophy of thymus and spleen with depletion of lymphoid cells, and edematous changes of uterus with desquamation of uterus mucosa as estrus cycles were detected throughout the whole experimental groups including both male and female vehicle controls. The significant (p<0.01) increases of absolute weights of kidney and pancreas detected in BSS extracts 1000 mg/kg-treated female group are considered as secondary changes from increases of body weights. The results obtained in this study suggest that the BSS extract is non-toxic in mice and is therefore likely to be safe for clinical use. The LD50 and ALD of BSS aqueous extracts in both female and male mice were considered as over 2000 mg/kg because no mortalities were detected upto 2000 mg/kg that was the highest dose recommended by KFDA and OECD. In addition, the MTD of BSS extracts was also considered as over 2000 mg/kg because no BSS extracts-treatment related toxicological signs were detected at histopathological observation except for BSS or their component-related pharmacological effects, the immunomodulating effects detected in the present study.

• Toxicological Research
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• 제33권2호
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• pp.149-156
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• 2017

The purpose of this study was to investigate the wound healing effect of acai berry water extracts (ABWE) and a possible underlying mechanism involved in its action using various in vitro and in vivo models. The wound healing effect of ABWE was evaluated by migration assay using HS68 fibroblast cells. In addition, its effect on mRNA expression of procollagen, fibronectin, and MMP-1 was determined. Moreover, the wound healing effect of ABWE was evaluated in in vivo wound models through macroscopic and microscopic observation. In addition, mRNA expression levels of wound related genes were determined. Results revealed that ABWE was not cytotoxic. It increased migration of HS68 fibroblast cells. ABWE increased mRNA expression levels of fibronectin but decreased the mRNA expression levels of MMP-1. ABWE also showed significantly potent wound healing effect in vivo based on macroscopic and histopathological observation and mRNA expression evaluation for wound related genes. Taken together, our results indicated that ABWE might have potential as a wound healing agent.

• 대한수의학회지
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• 제35권3호
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• pp.563-573
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• 1995

To know the effect of Ivermectin(IVM) toxicity in testis, histopathologic changes as well as clinical signs were observed in experimental animals including dogs by the subcutaneous injection with 3-50mg/kg of IVM. Clinically, it was observed to have depression and ataxia in all groups whereas tremor and coma in mice, rats and guinea pigs, coma in hamsters and rabbits, and tremor and salivation in dogs were shown. The clinical signs were different by the dosage of IVM, species and individuals in all animals. Susceptibility to IVM was most sensitive in dogs, especially in a Tosa dog and this was susceptible in mice, hamsters and rabbits, guinea pigs and rats in order. Microscopical observation revealed that the seminiferous tubules of testis had decreased thickness of germinal epithelium due to the necrosis and desquamation of the spermatids and spermatocytes. The progressive pattern by the times of administration showed vacuolar formation between the layer of spermatids and spermatogonia due to the marked necrosis of spermatocytes and the presence of multinucleated giant cells derived from spermatid throughout the seminiferous tubules of testis. Only a layer of spermatogonia, a few spermatogonia, and Sertoli cells wore observed with atrophied wavelike basement membrane in the seminiferous tubules of testis. Necrotic germinal cells, sloughed immature spermatids and spermatocytes were present in the lumen of epididymis and ductus deferens. Microscopical observation showed different susceptibility to IVM with clinical observation in which it was also most sensitive in dogs, especially in a Tosa dog and this was susceptible in rabbits and guinea pigs, hamsters, rats and mice in order. It was considered that IVM affects mainly spermatocyte or spermatid stage in the spermatogenesis and disturbs their developing beyond these stage.

• 대한수의학회지
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• 제59권1호
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• pp.17-24
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• 2019

Animal models of osteoarthritis (OA) have played a key role in understanding the etiology of OA and in the development of new therapeutic strategies. Although pigs have an advantage as an animal disease model due to their similarity to humans, there are few studies on the induction of OA in minipigs. Therefore, this study aimed to characterize disease progression of OA in total medial meniscectomy (TMM)-operated skeletally mature minipigs, up to day 180 postoperatively. There were no significant alterations in vital signs or hematological indices throughout the observation period. However, clinical manifestations of OA in the medial femoral condyles of TMM-operated minipigs were progressive, depending on postoperative duration, with respect to osteophytes formation and roughened surfaces on radiological observation, cartilage erosion under macroscopic examination, and severe cartilage defects including fibrillation, vertical fissures, and cartilage denuding on histopathological observation, with the highest score indicating late-stage OA on day 180 and without indicating apparent variation between subjects. In particular, the lateral femoral condyles were also degenerated, possibly due to localization of weight-bearing from both menisci to the lateral meniscus. Therefore, TMM in minipigs is suitable for reproducible induction of degenerative changes in the femorotibial joints that closely resemble late-stage OA, and is suitable for use in further research.

• Biomolecules & Therapeutics
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• 제16권2호
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• pp.137-140
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• 2008

The effects of Picrorrhiza Rhizoma (PR) aqueous extracts were observed on xylene-induced acute inflammation. The xylene was topically applied 60 min after administration of 500, 250 and 125 mg/kg of PR extracts, and all animals were sacrificed 2 hrs after xylene application. The changes on ear weights, histolopathological analyses of ear were evaluated as compared with indomethacin and dexamethasone 15 mg/kg treated groups - well known anti-inflammatory agents. Xylene application resulted in marked increases in induced ear weights as compared with intact control ear. Severe vasodilation, edematous changes of ear skin and increase in the thickness of the ear tissues as acute inflammation were detected in xylene-treated control ears at histopathological observation. However, these xylene-induced acute inflammatory changes were dosedependently decreased by oral treatment of PR extracts. Therefore, it is concluded that PR extracts has favorable anti-inflammatory effects on xylene-applicated acute ear inflamed mice.