• Title/Summary/Keyword: sprague dawley rats

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26-Week Repeated Dose Oral Toxicity Study of KCHO-1 in Sprague-Dawley Rats

  • Yang, Muhack;Lee, Seongjin;Wang, Tingting;Cha, Eunhye;Jang, Jongwon;Kim, Dongwoung;Song, Bong-Keun;Son, Ilhong;Kim, Joonyup;Kang, Hyung Won;Kim, Sungchul
    • Journal of Pharmacopuncture
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    • v.22 no.3
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    • pp.192-199
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    • 2019
  • Objectives: KCHO-1(Mecasin), also called Gamijakyakgamchobuja-tang originally, is a combination of some traditional herbal medicines in East Asia. This medicine has been used mainly for alleviating neuropathic pains for centuries in Korean traditional medicine. KCHO-1 was developed to treat pain, joint contracture and muscular weakness in patients with amyotrophic lateral sclerosis. This study was carried out to investigate the chronic toxicity of KCHO-1 oral administration in rats for 26 weeks. Methods: Sprague-Dawely rats were divided into four groups and 10 rats were placed in the control group and the high-dose group, respectively. Group 1 was the control group and the remaining groups were the experimental groups. In the oral toxicity study, 500 mg/kg, 1,000 mg/kg, and 2,000 mg/kg of KCHO-1 were administered to the experimental group, and 10 ml/kg of sterile distilled water was administered to the control group. Survival rate, body weight, feed intake, clinical signs, and visual findings were examined. Urinalysis, ophthalmologic examination, necropsy, organ weight, hematologic examination, blood chemical examination and histopathologic examination were performed. Results: Mortality and toxicological lesions associated with the administration of test substance were not observed in all groups. Conclusion: NOAEL(No observed adverse effect level) of KCHO-1 is higher than 2000 mg/kg/day. And, the above findings suggest that treatment with KCHO-1 is relatively safe.

Effects of taurine on plasma and liver lipids, erythrocyte ouabain sensitive Na efflux and platelet aggregation in Sprague Dawley rats

  • Park, In-Sun;Kang, Young-Hee;Kang, Jung-Sook
    • Nutrition Research and Practice
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    • v.1 no.3
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    • pp.200-205
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    • 2007
  • The effects of taurine on plasma and liver cholesterol, erythrocyte ouabain sensitive Na efflux and platelet aggregation were examined in Sprague Dawley rats fed control or 0.5% cholesterol with 0.2% cholate diet. Plasma and liver levels of total cholesterol were increased significantly (p<0.05) in rats fed cholesterol diet compared to the control, and taurine significantly decreased the elevated plasma level of cholesterol in rats fed cholesterol diet (p<0.05). HDL-cholesterol was decreased in groups fed the cholesterol diet regardless of taurine supplementation and the difference between groups with and without cholesterol was significant (p<0.01). Plasma triglyceride was decreased and liver triglyceride was increased both significantly (p<0.05) in rats fed cholesterol compared to the control. Plasma and liver triglyceride in rats fed taurine was decreased significantly compared to the control (p<0.05). Intracellular Na tended to be lower in rats fed cholesterol or taurine and higher in rats fed cholesterol plus taurine compared to the control. Na efflux through Na-K ATPase and the passive leak of Na was somewhat reduced in rats fed cholesterol or taurine and was augmented in rats fed cholesterol plus taurine compared to the control, which showed a similar trend to the intracellular Na. Taurine supplementation caused a suppression of Na efflux in groups fed control diet and restored the suppressed Na efflux in groups fed cholesterol. Platelet aggregation was significantly decreased in the group fed taurine compared to the control (p<0.05) and the group fed cholesterol plus taurine was also a little lower in aggregation than the group fed cholesterol. Microscopic examination showed that taurine prevented fatty liver in rats fed cholesterol diet. Taurine known for stimulating Na-K ATPase in some cell types rather decreased erythrocyte ouabain sensitive Na-K ATPase in the present study. Taurine had hypolipidemic and hypocholesterolemic effects and inhibited platelet aggregation which may be favorable for prevention of cardiovascular diseases.

The Effects of Chungpesagan-Tang Extracts on Reversible Forebrain Ischemia in Sprague-Dawley Rats (청폐사간탕(淸肺瀉肝湯)이 중대뇌동맥 폐쇄 후 재관류에 미치는 영향)

  • Oh, Yean-Hwan;Park, In-Sick;Shin, Gil-Cho;Lee, Won-Chul;Jeong, Sung-Hyun
    • The Journal of Internal Korean Medicine
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    • v.22 no.2
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    • pp.161-174
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    • 2001
  • Objectives : The purpose of this investigation is to evaluate the effect of Chungpesagan-Tang Extracts on reversible forebrain ischemia in Sprague-Dawley rats. Methods : the volume of cerebral infarction and edema, the pathohistological change of neurons, the number of survived neurons, neurotransmitters through immunohistochemical methods, proteins connected with neurotransmitters through immunohistochemical methods and the pathohistological change of neurons through electro-microscopy were investigated. From these reseach data, the protection of neurons and the activity of brain cells were examined. Results : 1. The infaction volume of the control group was 23.9%, and that of the sample group was 16%. 2. The brain edema volume of the control group increased by 17% compared to the normal group and that of the sample group increased by 10%. 3. The light microscopy revealed that the neurons in the ischemia-induced area and CA1 area of hippocampus were most heavily damaged and that the sample group was less damaged compared with the control group. Most pyramidal neurons died in 7 days when brain ischemia was induced. 4. The number of survived pyramidal neurons in the CA1 area of the hippocampus were studied. The normal group had 93 neurons/mm, survived the control group(after 3 days) had 21/mm, the control group(after 7 days) had 3/mm and the sample group 33/mm. 5. The immunohistochemical methods revealed that: (1) In the control group, the sensitivity of GABA, NOS, DBH were increased, and those of Synapsin, eEF-$1{\alpha}$ decreased. NOS and DBH had positive reactions in the control group, but negative in the normal group. (2) In thd sample group, the sensitivity of GABA, NOS, DBH were attenuated, and those of NPY, Synapsin, CaMKII, eEF-$1{\alpha}$ increased when compared to the control group. 6. The electro-microscopy revealed that most neurons died by necrosis and some neurons died by apoptosis. Several imflammation cells appeared in the injured area of neurons. The number of neurons in the sample group that died by ischemia decreased. But, the number that died by apoptosis did not significantly change. Conclusions : The data shows that the effect of Chungpesagan-Tang Extracts on reversible forebrain ischemia in Sprague-Dawley rats is significant.

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The Change of Food Intake in Morphine Treated Rat (몰핀이 흰쥐의 Food Intake 에 미치는 영향)

  • Kim, Ha-Rriet;Cho, Kang-Hee
    • Journal of Nutrition and Health
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    • v.17 no.4
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    • pp.313-319
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    • 1984
  • The effect of morphine on food intake on freely fed Sprague - Dawley rats was examined Opiate receptor binding assay was used to investigate the possibility of the opioid system involved in food intake regulation of normal rats. When rats were treated with 5mg morphine per kg body weight, subcutaneously, the food intake of the rats for the first 2 hours was increased 125% of the control rats. The effect of morphine on food intake of male and female rats were greater when the morphine was injected at 10 : 00 a.m than that in the rats administered the morphine at 4 : 00 p.m. The morphine effect was not significant in older rats and female was more responsive than male rats. In morphine treated rats, opioid receptor density has exhibited 33% reduction as measured by the $^{3}H-naloxone$ binding assay with whole brain homogenate. These results indicate that the increase of food intake by morphine for 2 hours after the injection may be mediated through the opioid system in rat brain.

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Chronic cerebral hypoperfusion and plasticity of the posterior cerebral artery following permanent bilateral common carotid artery occlusion

  • Cho, Kyung-Ok;Kim, Seul-Ki;Kim, Seong Yun
    • The Korean Journal of Physiology and Pharmacology
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    • v.21 no.6
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    • pp.643-650
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    • 2017
  • Vascular dementia (VaD) is a group of heterogeneous diseases with the common feature of cerebral hypoperfusion. To identify key factors contributing to VaD pathophysiology, we performed a detailed comparison of Wistar and Sprague-Dawley (SD) rats subjected to permanent bilateral common carotid artery occlusion (BCCAo). Eight-week old male Wistar and SD rats underwent BCCAo, followed by a reference memory test using a five-radial arm maze with tactile cues. Continuous monitoring of cerebral blood flow (CBF) was performed with a laser Doppler perfusion imaging (LDPI) system. A separate cohort of animals was sacrificed for evaluation of the brain vasculature and white matter damage after BCCAo. We found reference memory impairment in Wistar rats, but not in SD rats. Moreover, our LDPI system revealed that Wistar rats had significant hypoperfusion in the brain region supplied by the posterior cerebral artery (PCA). Furthermore, Wistar rats showed more profound CBF reduction in the forebrain region than did SD rats. Post-mortem analysis of brain vasculature demonstrated greater PCA plasticity at all time points after BCCAo in Wistar rats. Finally, we confirmed white matter rarefaction that was only observed in Wistar rats. Our studies show a comprehensive and dynamic CBF status after BCCAo in Wistar rats in addition to severe PCA dolichoectasia, which correlated well with white matter lesion and memory decline.

Single-dose Intravenous Toxicology Testing of Daebohwalryeok Pharmacopuncture in Sprague-Dawley Rats

  • Sun, Seung-Ho;Park, Sunju;Jeong, Jong-Jin;Lee, Kwang-Ho;Yu, Jun-Sang;Seo, Hyung-Sik;Kwon, Ki-Rok
    • Journal of Pharmacopuncture
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    • v.18 no.2
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    • pp.42-50
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    • 2015
  • Objectives: The aims of the study were to test the single- dose intravenous toxicity of Daebohwalryeok pharmacopuncture (DHRP) in Sprague-Dawley (SD) rats and to estimate the crude lethal dose. Methods: The experiments were conducted at Biotoxtech Co., a Good Laboratory Practice (GLP) laboratory, according to the GLP regulation and were approved by the Institutional Animal Care and Use Committee of Biotoxtech Co. (Approval no: 110156). The rats were divided into three groups: DHRP was injected into the rats in the two test groups at doses of 10 mL/kg and 20 mL/kg, respectively, and normal saline solution was injected into the rats in the control group. Single doses of DHRP were injected intravenously into 6 week old SD rats (5 male and 5 female rats per group). General symptoms were observed and weights were measured during the 14 day observation period after the injection. After the observation period, necropsies were done. Then, histopathological tests were performed. Weight data were analyzed with a one-way analysis of variance (ANOVA) by using statistical analysis system (SAS, version 9.2). Results: No deaths and no statistical significant weight changes were observed for either male or female SD rats in either the control or the test groups during the observation period. In addition, no treatment related general symptoms or necropsy abnormalities were observed. Histopathological results showed no DHRP related effects in the 20 mL/kg DHRP group for either male or female rats. Conclusion: Under the conditions of this study, the results from single-dose intravenous injections of DHRP showed that estimated lethal doses for both male and female rats were above 20 mL/kg.

Genetic heterogeneity of Pneumocystis carinii from rats of several regions and strains

  • Chung, Byung-Suk;Pars, Yun-Kyu;Huh, Sun;Yu, Jae-Ran;Kim, Jin;Shi, Xiaohua;Cho, Sang-Rock;Lee, Soon-Hyung;Hong, Sung-Tae
    • Parasites, Hosts and Diseases
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    • v.38 no.3
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    • pp.151-158
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    • 2000
  • Pneumocystis carinii is a major opportunistic pathogen which has been found in the lungs of a wide variety of mammalian host species, and the fact suggests the possibility of intraspecific variation. Until now, P. carinii from different mammalian species are differentiated as subspecies, and the rats are known to be infected by two subspecies. The present study investigated genetic heterogeneity of P. carinii isolates from two strains of rats in Korea and China by molecular karyotyping, RFLP and sequencing analysis. Karyotypes of P. carinii were grouped into three, two from two strains of rats In Korea and one from rats in China. However RFLP of PCR product of ribosomal and MSG gene of the P. carinii isolates showed same pattern. The sequence homology rates of ${\alpha}-tubulin$ DNA of the P. carinii isolates were 96% in Seoul Wistar rats, 93% in Seoul Sprague-Dawley rats, and 85% in Chinese Sprague-Dawley rats. The present finding confirmed that P. carinii from rats in Korea are grouped into two karyotype strains which are different from that of P. carinii from rats in China. The Chinese isolate shows a little different sequences of ${\alpha}-tubulin$ DNA.

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Carcinogen-DNA adducts in Liver and Bladder of Sprague-Dawley rats treated with benzidine in drinking water (벤지딘으로 오염된 음용수를 섭취한 흰쥐에서 간장세포와 방광세포에 형성된 발암물질- DNA adduct에 관한 연구)

  • 이진헌;신호상;장미선;홍춘표;최석남
    • Journal of Environmental Health Sciences
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    • v.27 no.3
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    • pp.63-70
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    • 2001
  • To identify and evaluate the benzidine-DNA adducts in liver and bladder, we exposed the 80 ppm benzidine to 40 sprague-dawley rats by drinking water for 4 weeks(6.2 mg/kg body wt./day). Only one benzidine-DNA adduct was found at the same site of thin layer chromatogram of $^{32}$ P-postlabeling method in the liver and bladder of exposed rats. So we know the DNA adduct formed at liver and bladder were similar to each other, which was N-(deoxyguanosin-8-yl)-N'-acetylbenzidine. Relative adduct labeling(RAL) of DNA adduct was similar to each other for 1 and 2 weeks, but that in liver was significantly higher than in bladder for 3 and 4 weeks. RAL$\times$10$^{9}$ of DNA adduct were 84.45$\pm$11.31 and 152.8$\pm$5.53 in liver, and were 24.76$\pm$7.06 and 38.00$\pm$10.57 in bladder for 3 and 4 weeks, respectively. Regression equation between liver and bladder was Y=-3.801+2.507 X(r=0.6036, p<0.01). In conclusion, benzidine-DNA adduct formed in liver was significantly higher than that in bladder, with the similar compound structure in sparague-dewley rates treated benzidine in drinking water.

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A study on myo-inositol transport system in peripheral nerve isolated from lead-intoxicated rat. (납 중독 랫드의 말초신경내 myo-inositol 수송 체계에 관한 연구)

  • 정명규;조해용
    • Journal of environmental and Sanitary engineering
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    • v.11 no.2
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    • pp.21-26
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    • 1996
  • In our previous studies, we reported that lead intoxicated nerve cell by inhibition of the Na$^{+}$-K$^{+}$ ATPase activity and reduction of myo-inositol in nerve cell. As the second series of experiments, in order to understand toxic mechanism of lead for nerve cell, the characteristics of myo-inositol transport system and the effect of lead on its system have been studied in the sciatic nerves of control and lead-treated rats. A lead intoxicated animal model was induced by feeding diet containing lead to Sprague-Dawley rat for two weeks. Four weeks aged Sprague-Dawley rats were divided into three group : normal control group, 10ppm-lead treated group, 100ppm-lead treated group. All rats were sacrified at the end of two weeks. The rate o myo-inositol transport by sciatic nerve isolated from lead-treated rat was significantly decreased compared with that of control rat. This deficit results from that myo-inositol transport system which is carrier mediated and sodium-potassium dependent was inhibited by the lead treatment (both 10ppm and 100ppm) due to increase of the Km value without affecting Vmax value for myo-inositol carrier. These observations suggest that the toxic mechanism of lead on nerve myo-inositol transport system might be a change of affinity without change of maximum transport velocity for carrier.

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Fumonisin $B_1$ induced renal toxicity in Sprague-Dawley rats

  • Lim, Chae-Woong;Yoon, Hyun-Sang;Rim, Byung-Moo
    • Korean Journal of Veterinary Pathology
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    • v.3 no.1
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    • pp.7-14
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    • 1999
  • We investigated the effect of a single intravenous dose of Fumonisin $B_1(FB_1$) of rat kidney on the time sequence. Male Sprague-Dawley rats were intravenouslyin jected with FB$_1$at 1.25 mg/kg and were euthanized at 12 hrs, 1, 2, 4, and 6 days after the injection. In $FB_1$ treated rats, serum BUN and creatinine were elevated from 12 hrs. Microscopically, the initial target site was tubules of inner stripe, with mild degenerative and necrotic changes at 12 hrs, but the tubules recovered on day 4. In outer stripe, there were only a few scattered necrotic cells on day 1. These changes became more obvious over the time passed and most severe on day 4. On day 6, regeneration occurred, manifest as hypertrophic, basophilic tubular cells. The dying cells were proved to necrotic cells instead of apoptotic cells by TUNEL. Ultrastructural changes were cytoplasmic vacuole, dilated endoplasmic reticulum, swollen mitochondria, ballooned microvilli of the tubular cell in the outer stripe. These results showed that the renal tubules of outer medulla were the target to $FB_1$-induced nephrotoxicity in the rat. However, initial target was mner stnpe of medulla.

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