• Korean Journal of Veterinary Research
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• v.23 no.1
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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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• v.32 no.4
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• pp.399-410
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• 2002

This study was performed to investigate the effects of Bambusae Caulis in Liquamen (bamboo extract) on the changes of antioxidant enzymes and histopathological changes of liver and kidney in mice when administered in different dosages. The experimental groups were divided into four. For control group, 0.9％ NaCl (0.2 ml/25 g B.W.) and for experimental groups, 5% (H1 group), 10% (H2 group), and 20%(H3 group) bamboo extract diluted with 0.9％ NaCl, were administered (0.2 ml/25 g B.W.) respectively for 28 days at an interval of 48 hours. MnSOD activities were increased in H1 group (46%, P<0.05), H2 group (40%, P<0.05), and H3 group (34%, P<0.05) as compared to the control group. CuZnSOD activities were increased in H1 group (11%, P<0.05), but were decreased in H3 group (13%, P<0.05). The activities of catalase were decreased in H1 group (39%, P<0.05), H2 group (34%, P<0.05), and H3 group (31%, P<0.05) as compared to the control group. Histopathological observation revealed ballooned hepatocytes in the pericentral and periportal veins of H1 group. More ballooned and injured hepatocytes than in H1 group were observed in the H2 and H3 groups. Detachment of endothelial cells of the central vein was observed in the H2 and H3 groups. These results indicated that bamboo extract developed dose-dependent changes in antioxidant enzyme activities and developed histopathological changes of liver and kidney.

• Journal of fish pathology
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• v.24 no.3
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• pp.225-236
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• 2011

This study was aimed to determine the fish physical status according to the gross and histopathological findings of liver in cultured black rock fish, Sebastes schlegeli. All 47 fish submitted had no marked abnormalities in the external findings. 42.55% of fish showed normal liver, 25.53% yellow liver, 25.53% atrophic brown liver, 4.26% yellowish-green liver and 2.13% fatty liver in gross examination. Grossly normal liver showed no remarkable change in lobular structure but many vacuoles were found in hepatic cell. Hepatic cells took normal roundish, polygonal shapes containing spherical nuclei. In group of yellow-brown liver, many brown pigments were seen in hepatic cells, MMCs and brown-colored hyaline droplets within cytoplasm of hepatocytes. Yellowish green pigments were seen in hepatic cells and MMCs of yellow green liver and green colored hyaline droplets within hepatocytes. The dilated central veins are highlighted with atrophy of hepatic cells. Outline of atrophic hepatocyte became ambiguous and nucleus frequently become small and pyknotic. Fatty liver showed prominent vacuolar structures in cells as clear spaces or foamy cytoplasm with degenerative nuclei. From these results, it was strongly suggested that hepatic gross and histological findings could be used as important and critical health parameters of fish prior to progression to substantial manifestation as clinical disease.

• Herbal Formula Science
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• v.16 no.1
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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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• v.23 no.6
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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.

• Journal of Physiology & Pathology in Korean Medicine
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• v.24 no.1
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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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• v.33 no.2
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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.

• Korean Journal of Veterinary Research
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• v.35 no.3
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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.

• Korean Journal of Veterinary Research
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• v.59 no.1
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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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• v.16 no.2
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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.