• Molecular & Cellular Toxicology
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• v.2 no.1
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• pp.48-53
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• 2006

[ ${\alpha}-Naphthylisothiocyanate$ ] (ANIT) induces intrahepatic cholestasis, involving damage to biliary epitheial cells. This study investigates hepatic gene expression and histopathological alterations in response to ANIT treatment in order to elucidate early time response of ANIT-induced hepatotoxicity. ANIT was treated with single dose (3, 6, and 60 mg/kg) in corn oil by oral gavage. Serum biochemical and histopathological observation were performed for evaluation of hepatotoxicity level. Affymetrix oligo DNA chips were used for gene expression profile by ANIT-induced hetpatoxicity. Hepatic enzyme levels (ALT, AST, and ALP) were increased in 24 hr high dose group. In microscopic observations, moderate hepatocellular necrosis, were confirmed 24 hr high dose groups. We found that gene expression patterns were dependent on time and dose. Our selected genes were related inflammation and immunomodulation. In this study, ANIT-induced hepatotoxicity was involved in acute phase responses and provides evidence for role of neutrophil could be mechanism associated with ANIT-mediated hepatotoxicity.

• The Journal of Internal Korean Medicine
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• v.29 no.4
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• pp.871-886
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• 2008

Objective : Gypsum fibrosum has been traditionally used in treatment of febrile diseases and recently been shown to have anti-inflammatory effect. Chronic renal failure has a serious clinical symptoms including proteinuria, azotemia, anemia, and hyperlipidemia and has characteristic histopathological changes, glomerular hypertrophy, infiltration of inflammatory cells, and crescentic sclerosis, We investigated the effects of gypsum fibrosum on renal functional and histopathological disorder in chronic renal failure rat model induced 5/6 nephrectomy. Methods : Using Sprague-Dawley rats, CRF was induced by 5/6 nephrectomy. The rats were divided into 3 groups, normal, conrol, and gypsum administered orally with gypsum fibrosum 500mg/kg/day. Body weight, 24 hr proteinuria, hematologic analysis, and histological morphologic changes were followed up after 8 weeks. The glomerular macrophage/monocyte infiltration, $TGF-{\beta}_1$, type IV collagen, and angiotensin II type1 receptor($AT_1$) were evaluated by immunohistochemistry. Resuls : In the CRF control group, functional parameters and histopathologic changes clearly indicated the development of CRF. 24 hr proteinuria significantly increased in the CRF control group over the normal group, and serum creatinine level was lower in the gypsum group than in the control group, LDL-cholesterol was significantly lower in the gypsum group than in the control group. Morphological investigations showed a variety of characteristic features of CRF, glomerular hypertrophy, increasing cellular density of glomerulus, deposition of extra-cellular matrix, fibrotic change, and glomerular sclerosis in the control group, but in the gypsum group, these features diminished significantly. In observation of renal type IV collagen and $AT_1$ expression, positive area significantly increased in the control group over the normal group, and it significantly decreased in the gypsum group compared to the control group. Conclusions : Our findings suggest that gypsum fibrosum inhibits $AT_1$ and type IV collagen expression in renal tissues and attenuates progression of glomerulosclerosis and interstitial fibrosis in chronic renal failure rats, which lead to amelioration of renal function. From these results, we suggest that gypsum fibrosum may have renoprotective effects and could be a useful remedy agent for treating chronic renal failure.

• Korean Journal of Veterinary Research
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• v.30 no.1
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• pp.93-102
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• 1990

Thirty-day-old piglets were intranasally or subcutaneously inoculated with 2ml of Aujeszky's disease virus, NYJ-1 strain, at the titer of $10^{6.75}$ $TCID_{50}/0.1ml$, that was isolated from the diseased piglets in Korea, and histopathological studies were performed to elucidate the pathognomonic characters of the isolate. Results obtained through the experiments were as follows: 1. Major clinical signs on the 2nd and 3rd days post inoculation (p.i.) were fever, anorexia and dyspnea. On the 6th and 7th days p.i., nervous signs, severe dyspnea and salivation were observed in the group of intranasal inoculation, and one out of 3 piglets in this group died on the 7th day p.i.. General signs were more severe in the group of intranasal inoculation than the group of subcntaneous injection. Between the 8th and l0th days p.i., the signs subsided and the piglets were completely recovered from the illness. 2. Hematologically, most of the inoculated pigs showed a mild lymphocytopenia on the 5th and 6th days p.i.. 3. By necropsy, swelling and hemorrhagic lesions were observed in tonsil, central nervous system and lung. No specific changes were grossly found in other parenchymatous organs. 4. In histopathological study, degeneration and necrosis of nervous cells, non-suppurative meningoencephalitis, diffuse or focal gliosis, perivascular cutting and degeneration of ganglion cells were observed in central nervous system, and swelling and hemorrhagic changes were shown in the tissues of liver, lung and lymph nodes. 5. By indirect immunofluorescence antibody assay using ADV-monoclonal antibody, specific ADV antigens were detected in the tissues of tonsil, brain and spleen of the succumbed piglet. However, in the experimentally slaughtered piglets, the specific reactions were noted only in the tonsils.

• Korean Journal of Veterinary Service
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• v.21 no.1
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• pp.29-39
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• 1998

This study was carried out to investigate the prevalence of antibody against Toxoplasma gondii in the dog by Latex agglutination test and Indirect fluorescent antibody test. Two month-old dogs were infected intraperitoneally with T gondii to observe histopathological and immunohisto-chemical changes. Results obtained through this experiment were summarized as follows ; 1. Among the serum samples of 163 heads of the dog, 10 samples(6.1%) were positive. 2. In the sex, 6 heads (7.1%) out of 84 female dogs and 4 heads(5.1%) out of 79 male dogs were positive. However, there were no significant differences between the male and female. 3. Overall proportion of agreement between indirect fluorescent antibody and Latex agglutination test in 163 sera of dogs was 97.5%. 4. When 2 month-old dogs were infected intraperitoneally with T gondii, main clinical signs were intermittent fever, dyspnea, diarrhea. In general, the infected dogs recovered closely on the 11th day of post-inoculation. 5. At necropsy, petechial and ecchymotic hemorrages and swelling in small intestine, lung, spleen, liver and kidney were observed. 6. In histopathological observation, interstitial pneumonia, hyperemia and hemorrhages in lung were observed. Focal necrosis of hepatocytes, the neutrophil and basophil in the renal tubular epithelium were observed. 7. By immunohistochemical staining using Vectorstain ABC kit, the positive cells were recognized in the lung and the liver. 8. By indirect fluorescent antibody test, the Toxoplasma antibodies in the infected dogs were detected on the 15th day of postinoculation.

• The Korea Journal of Herbology
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• v.25 no.3
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• pp.117-121
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• 2010

Objective：The Herbal Remedy for Diabetes Mellitus-01 (HRDM-01) is composed of 11 species of medicinal plants. HRDM-01 is used as anti-hyperglycaemic agent. Anti-hyperglycaemic agents in western medicine often have hepatotoxicities. Therefore, we investigated safety of HRDM-01, especially in liver functions. Methods：We investigated the effects of HRDM-01 on liver function measuring serum AST, ALT and LDH levels and histopathological changes of liver tissue using photomicroscope. In addition, we also investigated the effects on serum lipid levels such as total cholesterol, HDL-cholesterol and triglyceride. Results：In our experiment, single injection of streptozotocin elevated levels of AST and ALT in serum. But LDH level was not affected. In addition, our animal model showed elevated levels of total cholesterol and triglyceride in serum. 30 days treatment with HRDM-01 lowered serum AST level. Serum levels of ALT and LDH did not affected. In addition, HRDM-01 lowered serum triglyceride level significantly. In histopathological observation, we did not find any abnormal changes in all experimental groups. Conclusions：Briefly, HRDM-01 did not elevate serum levels of ALT, LDH, total cholesterol and did not affect histopathological changes in liver tissues. Moreover, HRDM-01 lowered serum AST, triglyceride, which are elevated by induction of diabetes mellitus. These results suggest the safety of HRDM-01 in diabetic treatment.

• The Korean Journal of Pain
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• v.25 no.4
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• pp.228-237
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• 2012

Background: Milnacipran is a balanced serotonin norepinephrine reuptake inhibitor with minimal side effects and broad safety margin. It acts primarily on the descending inhibitory pain pathway in brain and spinal cord. In many animal studies, intrathecal administration of milnacipran is effective in neuropathic pain management. However, there is no study for the neurological safety of milnacipran when it is administered neuraxially. This study examined the neurotoxicity of epidural milnacipran by observing behavioral and sensory-motor changes with histopathological examinations of spinal cords in rats. Methods: Sixty rats were divided into 3 groups, with each group receiving epidural administration of either 0.3 ml (3 mg) of milnacipran (group M, n = 20), 0.3 ml of 40% alcohol (group A, n = 20), or 0.3 ml of normal saline (group S, n = 20). Results: There were no abnormal changes in the behavioral, sensory-motor, or histopathological findings in all rats of groups M and S over a 3-week observation period, whereas all rats in group A had abnormal changes. Conclusions: Based on these findings, the direct epidural administration of milnacipran in rats did not present any evidence of neurotoxicity in behavioral, sensory-motor and histopathological evaluations.

• Toxicological Research
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• v.22 no.1
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• pp.55-59
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• 2006

The purpose of this study was to investigate the toxicity of hematoporphyrin-coated magnetic ferrofluid (HP-MF) through intravenous administration in Sprague-Dawley rats. Each group was treated with either saline, or the HP-MF at 0.5, 1, 1.5, 2 and 4 ml/kg body weight (b.w.) for the observation of survival rate, clinical symptoms, laboratory values and histopathological findings. In this study, HP-MF was evaluated for the survival rates, symptoms, laboratory values and histopathological examination after treatments. The result revealed that the animals in the group of HP-MF at 2 and 4 ml/kg b.w. showed some lethality. In serum biochemistry, the levels of AST, ALT and ALP were increased in the MF and HP-MF treated groups. However, histopathological examination for the suspected organs showed no evidence of hepatotoxicity and nephrotoxicity of typical iron poisoning. Though the toxicity of HP-MF was higher than that of HP, long retention of hematoporphyrin via HP-MF provides additional benefit over conventional hematoporphyrin. HP-MF could be utilized as a potential photodynamic agent in cancer therapy. It is suggested to develop an efficient external magnetic device to attract hematoporphyrin in the target site, thereby enabling to administering a small amount of HP-MF.

• Journal of Physiology & Pathology in Korean Medicine
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• v.28 no.6
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• pp.636-642
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• 2014

In the theory of Korean medicine, Angelicae Dahuricae Radix (ADR) can expel wind and relieve exterior syndrome, and eliminate dampness. Recently, ADR has been reported to have possibilities as anti-inflammatory agent and cosmetics. The purpose of this study is to evaluate the efficacy of ADR on contact dermatitis (CD). In order to investigate the anti-inflammatory effects of ADR on CD, we investigated the effects of ADR on ear thickness, ear weight, skin lesion and histopathological changes in mice with CD induced by 1-fluoro-2,4-dinitrofluorobenzene (DNFB). In addition, the effect on spleen weight was also measured. In our results, topical application of ADR lowered ear thickness and weight respectively. ADR treatment also improved skin lesions such as erythema and scale. In the histopathological observation, ADR-treated group showed diminished epidermal hyperplasia and immune cell infiltration in inflammed tissues compared to those of non-treated control group. In conclusion, These data suggest that ADR has anti-inflammatory action in inflammed skin tissue, resulting in improving skin lesion and histopathological abnormalities of CD.

• Journal of Korean Society of Occupational and Environmental Hygiene
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• v.29 no.4
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• pp.508-516
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• 2019

Objectives: The present study was performed to obtain acute toxicity information on glyoxal in male rats after intratracheal instillation. Methods: In order to calculate the LD₅₀ of glyoxal using Probit analysis with SAS, the test article was one intratracheal instillation to male Sprague-Dawley rats at dose levels of 0, 225, 451 or 902 mg/kg. During the test period, mortality, clinical signs, and body and organ weights were examined. At the end of the 14-day observation period, all animals were sacrificed and complete gross postmortem and histopathological examinations were performed. Results: Four animals of the 902 mg/kg group died within one week after the administration of glyoxal. All treatment group in a dose dependent manner, decreased body weight was found during the study period. The absolute and relative lung weight, and histopathological changes (bronchiolar-alveolar hyperplasia, chronic inflammation) of lung exhibited an increased in glyoxal treated groups in a dose dependent manner. However, there were no changes on the organ weights and histopathological changes of any other organ except lung. Conclusions: The results obtained in the present study suggest that the LD₅₀ in male Sprague-Dawley rats after a single intratracheal instillation of glyoxal was considered to be 866.9 mg/kg and the lung was found to be the target organ for glyoxal.

• Korean Journal of Veterinary Pathology
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• v.5 no.1
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• pp.9-16
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• 2001

To investigate the effects of safflower seed supplementation diet on the hepatic injury of rats administered with carbon tetrachloride (CCI$_4$), histopathological changes were assessed following acute and chronic administration in rats. In acute cases, all rats in group fed with 10% safflower seed supplementation diet survived despite the administration of lethal doses of $CCl_4$. However, most rats in group fed with control diet died. The hepatic injuries of survived rats, in the histopathological findings, were mild compared to those of dead rats. In the chronic cases, livers of group 2 fed with control diet were more progressive in fatty changes and centrilobular necrosis than those of group 3 fed with 20%safflower seed diet. However, after six weeks, livers of group 2 and 3 showed severe necrosis and mild fibrosis at the same time. Group 5 fed with 10% safflower seed supplementation diet and water containing 0.05% phenobarbital sodium showed mild fatty changes and necrosis compared with group 4 fed with control diet and water containing 0.05% phenobarbital sodium at sixth week. At 8 to 10 wee71s after the administration of $CCl_4$, severe fibrosis. fatty changes and marked necrosis were observed in group 4, but hepatic injuries were less severe in group 5. The present results suggested that safflower seed has some protective effect in hepatic lesions and consequently delay the progression of hepatic fibrosis.