• Biomolecules & Therapeutics
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• 제2권3호
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• pp.213-222
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• 1994

The acute tonicity of DWP305 (Ursodeoxycholic acid : Silymarin : Fursulthiamine : Riboflavin tetrabutyrate=1: 1 : 0.1 : 0.05) was evaluated in both sexes of Sprague-Dawley rats, 6weeks old by the oral route of administration. DWP305 was not considered to induce any toxic effect on the rats in mortalities, clinical findings, body weights and gross findings. It is suggested that LD$_{50}$ value in rats would be above 5 g/kg in the oral administration. Subacute toxicity of DWP305 was examined in Sprague-Dawley rats. Four groups of rats were administered orally at doses of 0, 0.32, 0.8, and 2.0 g/kg/day of DWP305 for one month. Any significant toxic clinical symptom was not observed in the treated rats during the experimental period. Macroscopic examination on the organs of tested animals showed no abnormal findings. On autopsy, no significant changes were found in organs examined. Maximum tolerated dose of DWP305 for the rat was estimated to be above 2 g/kg in this study.y.

• Biomolecules & Therapeutics
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• 제4권4호
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• pp.354-363
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• 1996

This study was conducted to investigate the repeated dose toxicity of DA-9601, an antiulcer agent of Artemisia app. extract, in rats. DA-9601 was administered orally once a day for 4 weeks to 10 males and 10 females per group at doses of 0(vehicle control), 125, 500 or 2000 mg/kg/day. Throughout the study, no treatment-related deaths and clinical signs were observed. In female rats receiving 125 mg/kg of DA-9601, water consumption increased slightly on day 4, 11 and 25. Hematological examination showed a decrease of MCV and an increase of PLT in male rats at the doses of 500 and 2000 mg/kg groups. Blood biochemistry revealed slight decreases of cholesterol, BUN and Na in male rats and decreases of total bilirubin and creatinine and slight increases of globulin and Cl in female rats. The organ weights at the end of 4 weeks showed slight changes in some organs of treated groups. But, all these changes were not considered to be of toxicological importance, because they did not show dose-response relationship and relevance to gross and microscopic findings. Histopathologically, abnormal treatment-related changes were not observed in any organ and target organs were not detected. On the basis of these results, the NOAEL(no-observed-adverse-effect level) of DA-9601 was estimated to be more than 2000 mg/kg/day under the conditions tested.

• Journal of Acupuncture Research
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• 제31권1호
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• pp.105-110
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• 2014

Objectives : The objective of this study is to analyze the single-dose toxicity of horse placenta hydrolysate extracts. Methods : Sprague-Dawley rats were chosen for the study. Doses of horse placenta hydrolysate extracts, 2,000 mg/kg, 1,000 mg/kg and 500 mg/kg, were administered to the experimental group, and the same doses of normal saline solution were administered to the control group. This study was conducted under the approval of the Institutional Animal Ethics Committee. Results : In all 4 groups, no deaths occurred, and the horse placenta hydrolysate extracts administered by oral was over 2,000 mg/kg. No significant changes in the weight between the control group and the experimental group were observed. To check for abnormalities in organs and tissues, we used microscopy to examine representative histological sections of each specified organ, the results showed no significant differences in any organs or tissues. Conclusions : The above findings suggest that treatment with horse placenta hydrolysate extracts is relatively safe. Further studies on this subject should be conducted to yield more concrete evidence.

• 한국가축번식학회지
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• 제25권1호
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• pp.35-42
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• 2001

본 연구는 Cu중독이 rat의 생리현상에 미치는 영향을 구명하고자 연속적인 Cu투여가 사료와 물섭취량, 증체량, 혈액치 및 장기내 무기물 잔류수준의 변동을 측정하였다. 1. 황산Cu 1,000, 2,000 및 4,000 ppm/kg을 rat에 투여했을 때 사료섭취량은 정상대조군에 비해 점차 감소하였고 용량이 증가할수록 사료 섭취량은 유의하게 감소하였다. 2. 황산Cu 1,000, 2,000 및 4,000 ppm/kg을 rat에 투여했을 때 음수량은 정상대조군에 비해 점차 감소하였고 황산Cu 용량이 증가할수록 음수량은 감소하는 경향을 나타냈으나 유의한 변화는 인정되지 않았다. 3, 황산Cu 1,000, 2,000 및 4,000 ppm/kg을 rat에 투여했을 때 증체량은 정상대조군에 비해 약간의 감소를 나타냈으나 황산Cu용량이 증가할수록 증체량은 점차 감소하였다. 4. 황산Cu 1,000, 2,000 및 4,000 ppm/kg을 rat에 투여했을 때 정상대조군에 비해 혈액치중 RBC 및 WBC치는 유의한 증가경향을 나타냈고, Hb량과 PCV치는 약간 감소하는 경향을 나타냈다. 한편, PLT치는 정상대조군에 비해 유의한 증가경향을 나타냈다. 5. 황산Cu 2,000 및 4,000 ppm/kg을 rat에 투여했을 때 간내 Cu, Mn, Fe, Pb 및 Zn의 잔류함량은 정상대조군에 유의한 증가를 나타냈다. 황산Cu 2,000 및 4,000 ppm/kg을 rat에 투여했을 때 신장내 Cu의 함량은 대조군에 비해 감소하였고, Mn, Fe, Pb, Zn의 함량은 정상 대조군에 비해 증가를 나타냈다.

• 한국가축번식학회지
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• 제25권2호
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• pp.139-145
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• 2001

본 연구는 Pb중독이 rat의 생리현상에 미치는 영향을 구명 하고자 연속적 인 Pb acetate 투여가 사료와 물섭취량, 증체량, 혈액치 및 장기내 무기물 수준의 변동을 측정하였다. 1. Pb acetate 1,000, 2,000 및 4,000 ppm/kg을 rat에 투여했을 때 사료섭취량은 정상대조군에 비해 점차 감소하는 경향을 나타냈고 용량이 증가할수록 사료섭 취 량은 유의 한 감소를 나타냈다. 2. Pb acetate 1,000, 2,000 및 4,000 ppm/kg을 rat에 투여했을 때 음수량은 정상대조군에 비해 점차 감소하는 경향을 나타냈고 Pb 용량이 증가할수록 음수량은 감소하였다. 3. Pb acetate 1,000, 2,000 및 4,000 ppm/kg을 rat에 투여했을 때 증체량은 정상대조군에 비해 약간 감소된 수준을 나타냈으나 Pb용량이 증가할수록 증체량은 점차 감소하였다. 4. Pb acetate 1,000, 2,000 및 4,000 ppm/kg을 rat에 투여했을 때 혈액치중 RBC, WBC 및 PLT치는 정상대조군에 비해 유의한 증가를 나타냈고, Hb량과 PCV치는 정상대조군에 비해 약간 감소를 나타냈다. 5. Pb acetate 2,000 및 4,000 ppm/kg을 rat에 투여했을 때 간내 Pb, Mn, Fe, Pb 및 Zn의 잔류함량은 정상대조군에 유의한 증가를 나타냈다. Pb 2,000 및 4,000 ppm/kg을 rat에 투여했을 때 신장내 Pb, Mn, Fe, Pb, Zn의 함량은 정상대주군에 비해 증가를 나타냈다.

• 한국환경보건학회지
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• 제33권4호
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• pp.306-316
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• 2007

This study have a object to found out the effects of oriental herb medicine, Antaeeum, to dams of rats and their offsprings. The Antaeeum was savaged to female Sprague-Dawley rats at a dose of 5 mg/kg/day for 3 weeks during gestation periods. Dams of rat were sacrificed at 20th day of gestation, and were observed major internal and reproductive organs. Approximately live fetuses in the 20th days of gestation were selected randomly and examined with stereo microscopes. Others offsprings were fixed with 95% ethanol for skeletal examinations. The fixed fetuses were stained with alcian blue and alizarin red S to observe skeletal variations or malformations. Maternal body weight of Antaeeum treated dams have a tendency of increasing compared with control dams. There were no significant difference in internal and reproductive organs of weight or findings. The spleenic organ relative weight of treated dams were decreased compared with the control significaltly (p<0.05). There were no significant changes between two groups in blood chemistry and hematological values. There were no significant changes in number of corpus luteum, implantation, live fetuses and implantation rate, delivery rate, late resorption rate and sex ratio. But in the Antaeeum treated group showed lower early resorption rate than that of the control dams. Fetal body weight and number of fetus a dam at Antaeeum treated group were higher than that of control group. The fetuses of dams treated with Antaeeum didn't induced external malformations. Vertebral and sternal variations were observed in Antaeeum group, but compared with the control, those variations were not significant. The ossification numbers of rib, cervical, thoracic, and lumber were normal. Fetuses treated with Antaeeum to the dams showed no significant difference in the number of caudal vertebra (P>0.01). From these results, it can be concluded that Antaeeum showed no toxicity effects on maternal side especially on body weight, early resorption rate, and number of live fetuses. Also there were no significant changes on maternal organ weights except spleen, hematological data, reproductive organs. Although skeletal variations were examined at vertebra and sternum, this Antaeeum could not induced significant choses in bone malformation.

• Clinical and Experimental Reproductive Medicine
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• 제23권3호
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• pp.269-275
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• 1996

Biosynthesis and secretion of anterior pituitary hormones are under the control of specific hypothalamic stimulatory and inhibitory factors. Among them, Growth Hormone Releasing Hormone (GHRH) is the major stimulator of pituitary somatotrophs activating GH gene expression and secretion. Human GHRH is a polypeptide of 44 amino acids initially isolated from pancreatic tumors, and the gene for the hypothalamic form of GHRH is organized into 5 exons spanning over 10 kilobases (kb) on genomic DNA and encodes a messenger RNA of 700-750 nucleotides. Several neuropeptides classically associated with the hypothalamus have been found in the extrahypothalamic regions, suggesting the existence of novel sources, targets and functions. GHRH-like immunoreactivity has been found in several peripheral sites, including placenta, testis, and ovary, indicating that GHRH may also have regulatory roles in peripheral reproductive organs. Furthermore, higher molecular weight forms of the GHRH transcripts were identified from these organs (1.75 kb in testis; 1.75 and >3 kb in ovary). These tissue-specific expression of GHRH gene suggest the existence of unique regulatory mechanism of GHRH expression and function in these organs. In fact, placenta-specific and testis-specific promoters for GHRH transcripts which are located in about 10 kb upstream region of hypothalamic promoter were reported. The use of unique promoters in extrahypothalamic sites could be refered in a different control of GHRH gene and different functions of the translated products in these tissues. Somatotrophs and lactotrophs have been thought to be derived from a common bipotential progenitor, the somatolactotrophs, which give origins to either phenotypes. Although the precise mechanism responsible for the lactotroph differentiation in the anterior pituitary gland has not been yet clalified, there are several candidators for the generation of lactotrophs. In human, the presence of GHRH peptides with different size from authentic hypothalamic form in the normal anterior pituitary and several types of adenoma were demonstrated. Recently our group found the existence of immunoreactive GHRH and its transcript from the normal rat anterior pituitary (gonadotroph> somatotroph> lactotroph), and the GHRH treatment evoked the increased proliferation rate of anterior pituitary cells in vitro. The transgenic mouse models clearly shown that GHRH or NGF overexpression by anterior pituitary cells induced development of pituitary hyperplasia and adenomas particularly GH-oma and prolactinoma. Taken together, we hypothesize that the pituitary GHRH could serve not only as a modulator of hormone secretion but as a paracrine or autocrine regulator of anterior pituitary cell proliferation and differentiation. Interestingly enough, the expression of Pit-1 homeobox gene (the POU class transcription factor) was confined to somatotrophs, lactotrophs and somatolactotrophs in which GHRH receptors are expressed commonly. Concerning the mechanism of somatolactotroph and lactotroph differentiation in the anterior pituitary, we have focused following two possibilities; (1) changes in the relative levels or interactions of both hypothalamic and intrapituitary factors such as dopamine, VIP, somatostatin, NGF and GHRH; (2) alterations of GHRH-GHRH receptor signaling and Pit-1 activity may be the cause of lactotroph differentiation or pituitary hyperplasia and adenoma formation. Extensive further studies will be necessary to solve these complicated questions.

• 한국발생생물학회지:발생과생식
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• 제17권4호
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• pp.435-440
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• 2013

Previous studies, including our own, have demonstrated that the intratesticular injection of hypertonic saline (20%) decreased serum testosterone level which was similar to the surgical castration in the rat, showing the state of chemical castration. In the present study, we further verify the efficacy of this less invasive method as an alternative of surgical orchidectomy in the andrological field. Sterilized 20% saline was directly injected into the adult male rats (750 ${\mu}l$ per testis). The tested rats were divided into 3 groups including intact group (intact), orchidectomy group (ORX) and saline injection group (SAL) after bilateral orchidectomy was performed at the same day of injection. All rats were sacrificed at 4 weeks after injection. The reproductive organs (testes, epididymis, seminal vesicles and prostates) were collected and used for DNA and protein pattern analyses. Also, patho-histological studies on the testes were performed. In contrast to the intact group, similar DNA damages of testis and seminal vesicle were appeared in ORX group and SAL group. The DNA degradations seemed to be the results of necrosis rather than apoptosis. In the protein pattern analysis, all the testing tissues exerted similar patterns in the ORX group and the SAL group compared to the those of intact group. Patho-histological studies revealed that severe degenerative changes in testicular seminiferous tubules and massive infiltration of immune cells in SAL group. The present study confirmed that direct injection of hypertonic saline into the testis caused the equivalent biochemical changes in the accessory sex organs as shown in the orchidectomized animals. These results suggest that hypertonic saline injection model could be a useful castration model which can substitute for surgical castration when its safety is secured through further study in the future.

• Journal of Nutrition and Health
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• 제27권1호
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• pp.12-22
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• 1994

Effects of very low level of lead in diet and exposure time on the accumulation and distribution in organs and tissues was investigated with growing rats. 21 days old Sprague-Dawley rats were exposed to lead for 7, 14 and 21 days by feeding of 0.03, 0.42, 0.92 and 1.46mg/kg Pb as Pb-acetate containing diet, respectively. Lead concentrations in blood, liver, kidney and bone exhibit a linear relationship with lead levels in diet. After 7 days of exposure, the greatest dose dependent accumulation of lead was found in kidney and followed in bone. However, after 14 and 21 days, the dose dependent accumlation of lead in bone was about two fold greater than that in kidney. The accumulation of lead in liver and blood was relatively low. As continuous exposure to lead, the concentrations of lead in liver, kidney, blood and intestinal tracts were rather not increased with exposure time. However, bone lead concentration was increased with exposure time by feeding of 0.92 and 1.46mg/kg Pb in diet, but not 0.42mg/kg. The lead concentration in gastrointestinal tracts tends also to increasing with lead levels in diet after 7 and 14 days of exposure. However, by 21 days of exposure the lead concentration revealed relatively constant value regardless of the dietary lead levels. It is concluded that the binding capacity of the lead in blood, liver, kidney and bone seems to be increased with increasing lead levels in diet. The lead concentration in these organs, with the exception of the lead in bone, seems, however, to be standing under steady state regulation by continued exposure with the same dietary lead level. Therefore, by chronic exposure condition with environmental relevant lead level bone might be a principle targe organ for lead and blood lead repesents better the current lead exposure than the lead body burden.

• 대한약침학회지
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• 제14권1호
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• pp.5-24
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• 2011

Objective: This study was performed to analyse four weeks repeated -dose toxicity of Sweet Bee Venom (SBV-pure melittin, the major component of honey bee venom) in rats. Methods: All experiments were conducted under the regulations of Good Laboratory Practice (GLP) at Biotoxtech Company, a non-clinical study authorized institution. Male and female rats of 5 weeks old were chosen for the pilot study of four weeks repeated-dose toxicity and was injected at the level of 0.56 mg/kg body weight (eighty times higher than the clinical application dosage as the high dosage), followed by 0.28 and 0.14 mg/kg as midium and low dosage, respectively. Equal amount of normal saline was injected as the control group every day for four weeks. Results: 1. No mortality was witnessed in all of the experiment groups. 2. All experiment groups appealed pain sense in the treating time compared to the control group, and side effects such as hyperemia and movement disorder were observed around the area of injection in all experiment groups, and the higher dosage in treatment, the higher occurrence in side effects. 3. Concerning weight measurement, neither male nor female groups showed significant changes compared to the control group. 4. Concerning to the CBC and biochemistry, all experiment groups didn't show any significant changes compared to the control group. 5. Concerning weight measurement of organs, experiment groups didn't show any significant changes compared to the control group. 6. To verify abnormalities of organs and tissues, those such as cerebellum, cerebrum, liver, lung, kidney, and spinal cords were removed and we conducted histologocal observation with H-E staining. Concerning the histologocal observation of liver tissues, some fatty changes were observed around portal vein in 0.56 mg/kg experiment group. But another organs were not detected in any abnormalities. 7. The proper high dosage of SBV for the thirteen weeks repeated test in rats may be 0.28 mg/kg in one time. Conclusion: Above findings suggest that SBV is relatively safe treatment medium. Further studies on the subject should be conducted to yield more concrete evidences.