• The Korea Journal of Herbology
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• v.32 no.1
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• pp.63-68
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• 2017

Objectives : HT042 is a combination of three herbal extracts from the roots of Astragalus membranaceus, the stems of Eleutherococcus senticosus and the roots of Phlomis umbrosa, which has been demonstrated to increase longitudinal bone growth rate. The aim of this study was to assess the safety of HT042 after repeated oral administration. Methods : A 14-day repeated oral dose toxicity study was conducted using male and female Sprague-Dawley rats. HT042 was administered orally at repeated doses of 500, 1,000 and 2,000 mg/kg/day for 14 days. Clinical signs and mortality were observed daily, whereas body weight and food consumption were recorded weekly throughout the experiment. At the end of the study, blood was taken from the posterior vena cava for hematology and serum biochemistry. All organs of the body surface, subcutis, head, thoracic cavity, and abdominal cavity were observed grossly. Then, the internal organs were removed and weighed. Results : No death occurred and no significant changes in clinical sign, body weight, food consumption and serum biochemistry parameters were observed in male and female rats over the study period. Although there were some alterations in hematologic and necropsy findings, and organ weights, these changes were not considered toxicologically significant. Conclusions : These results suggest that the 14-day repeated administration of HT042 does not produce any significant oral toxicity at doses of up to 2,000 mg/kg/day in male and female rats under the present experimental conditions.

• Journal of Animal Science and Technology
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• v.44 no.1
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• pp.39-44
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• 2002

The current study was conducted to investigate the effects of administration of antiserum against adipocyte plasma membrane(APM) proteins into rats on body fat mass. Twenty(20) male adult Sprague-Dawley rats were randomly allocated into either control or antiserum treatment group(10 rats/treatment) and immunized with physiological saline(control group) and polyclonal antiserum (treatment group), respectively, raised in sheep against rat APM proteins(5times, 2day interval). All animals were killed 4weeks after last injection. Intraperitoneal(i.p.) administration of antiserum significantly(P=0.0054 and P=0.0019, respectively) reduced subcutaneous(21.9%) and perirenal + mesentric + epididymic(36.0%) adipose tissue mass in rats of treatment group. Although body weights of antiserum treated rats were decreased during immunization, the rats recovered their body weight after 1 week of treatment. There were no significant changes in the level of blood glucose and in the contents of muscle protein and fat in antiserum treated animals. Current results indicate that polyclonal antibodies against APM proteins could be used to manipulate body fat mass in meat animals as well as laboratory animals. Further studies, however, are necessary for the practical applications of the current results.

• Journal of Pharmacopuncture
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• v.18 no.4
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• pp.45-50
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• 2015

Objectives: In this study, we investigated the 4-week repeated-dose oral toxicity of gami-jakyak gamcho buja decoction (Mecasin) to develop safe treatments. Methods: In order to investigate the 4-week oral toxicity of Mecasin, we administered Mecasin orally to rats. Sprague-Dawley (SD) rats were divided into four groups of five male and five female animals per group: group 1 being the control group and groups 2, 3, and 4 being the experimental groups. Doses of Mecasin of 500, 1,000, and 2,000 mg/kg of body weight were administered to the experimental groups, and a dose of normal saline solution of 10 mL/kg was administered to the control group. We examined the survival rate, weight, clinical signs, and gross findings for four weeks. This study was conducted under the approval of the Institutional Animal Ethics Committee. Results: No deaths occurred in any of the four groups. No significant changes in weights or food consumption between the control group and the experimental groups were observed. Serum biochemistry revealed that some groups showed significant decrease in inorganic phosphorus (IP) (P < 0.05). During necropsy on the rats, one abnormal macroscopic feature, a slight loss of fur, was observed in the mid dosage (1,000 mg/kg) male group. No abnormalities were observed in any other rats. In histopathological findings, the tubular basophilia and cast of the kidney and extramedullary hematopoiesis of the spleen were found. However, those changes were minimal and had occurred naturally or sporadically. No other organ abnormalities were observed. Conclusion: During this 4-week, repeated, oral toxicity test of Mecasin in SD rats, no toxicity changes due to Mecasin were observed in any of the male or the female rats in the high dosage group. Thus, we suggest that the doses in a 13-week, repeated test should be 0, 500, 1,000, and 2,000 mg/kg respectively.

• Development and Reproduction
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• v.2 no.2
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• pp.135-140
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• 1998

Protease Nexin-1 (PN-1) inhibits the activity of several serine proteases including thrombin, urokinase (uPA)-type plasminogen activator and trypsin. Tissue- and reproductive organ-specific mRNA levels of the PN-1 were investigated in Sprague-Dawley adult rat. PN-1 mRNA expression in rats was found in brain (forebrain, hindbrain), heart, liver, lung, ovary and oviduct. The level of PN-1 mRNA in male and female among the tissues was the highest in forebrain of the female. PN-1 expression in reproductive organs was found only in ovary and oviduct. These results suggest that PN-1 expression is dependent on the sex and may be related to folliculogenesis and early embryogenesis.

• Imaging Science in Dentistry
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• v.33 no.3
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• pp.161-169
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• 2003

Purpose: To observe the histologic changes and clusterin expression in the acinar cells of the submandibular gland in streptozotocin-induced diabetic rat following irradiation. Materials and Methods: Mature Sprague-Dawley rats were divided into three groups: control, diabetic, and diabetic-irradiated groups. Diabetes mellitus was induced in the Sprague-Dawley rats by injecting streptozotocin, while the control rats were injected with citrate buffer only. After 5 days, rats in diabetic-irradiated group were irradiated with single absorbed dose of 10 Gy to the head and neck region. The rats were killed at 1, 3, 7, 14,21, and 28 days after irradiation. The specimen including the submandibular gland were sectioned and observed using histologic and immunohistochemical methods. Results : Morphologic change of acinar cells was remarkable in the diabetic group, but was not observed in the diabetic-irradiated group. Necrotic tissues were observed in the diabetic-irradiated group. Coloring of toluidine blue stain was most increased at 14 days in the diabetic group, however there were no significant change throughout the period of the experiment in the diabetic-irradiated group. Expression of clusterin was most significant at 14 days in the diabetic group, but gradually decreased with time after 7 days in the diabetic-irradiated group. Degeneration of clusterin was observed in the diabetic-irradiated group. Conclusion : This experiment suggests that the acinar cells of submandibular gland in rats are physiologically apoptosed by the induction of diabetes, but that the apoptosis is inhibited and the acinar cells necrotized after irradiation.

• Journal of Oriental Neuropsychiatry
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• v.23 no.3
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• pp.143-160
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• 2012

Objectives : To provide information on the safety of ACM, we carried out a 13-week repeated oral dose toxicity and a 4-week recovery test of ACM in Sprague-Dawley rats. Methods : Female and male rats were treated with ACM with oral doses of 800, 2000, and 5000 mg/kg. The ACM was administered for 13 weeks. Mortality, clinical signs, body weight changes, food consumption, ophthalmologic findings, urinalysis, hematological and biochemical parameters, gross findings, organ weights and histological markers were monitored during the study period. Moreover, the rats were monitored for 4 extra weeks to determine recovery time after the study period. Results : We found no mortality and no abnormalities in clinical signs, body weight, food consumption, ophthalmologic findings, urinalysis, hematological and biochemical parameters, gross findings, organ weights and histological markers in any of the rats tested. Conclusions : The no-observed adverse effects level (NOAEL) was considered as over 5000 mg/kg for male and female rats.

• Journal of Nutrition and Health
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• v.37 no.4
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• pp.266-272
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• 2004

This study investigated the effects of soyoligosaccharide consumption on lipid profile of plasma, liver and feces and immune responses in Sprague-Dawley male rats. Sixty male Sprague-Dawley rats 4-wk-old were provided the soyo-ligosaccharide containing diets for 4 weeks (0, 100 g/kg diet); each of these diets was supplemented with either 70 or 200 g fat/kg diet, giving a total of 4 experimental groups. The effect of weight reduction was most significantly observed in the group fed low fat and soyoligosacchairde diet. The plasma total lipid and cholesterol contents were not changed by either fat proportion or soyoligosaccharide supplementation in the diets. Also the plasma triglyceride lowering effect by soyoligosaccharide was not observed in rats fed either low fat or high fat diet. However, the significant decrease in TG contents was found with rats fed high fat diets compared to the control/no soyoligosaccharide diet. Elevation of plasma LDL-cholesterol and reduction of HDL-cholesterol by feeding high fat diet was not altered by supplementing soyoligosaccharide. This was also applied to the liver lipid profiles. The significant increases in liver total lipid, trigly-cerides and cholesterol by high fat diet was not abolished by feeding soyoligosaccharide. However, the desirable effects of feeding soyoligosaccharide were found with total lipid and cholesterol excretion through feces in rats fed high fat diets. Immune organ weights and spleen cell proliferations did not affected by experimental diets. These results de-monstrated that soyoligosaccharide intakes increased the lipid output via feces, especially in rats fed the high fat diet, but more researches are needed on immune responses.

• Nutrition Research and Practice
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• v.3 no.2
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• pp.89-94
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• 2009

The aim of this study was to investigate if dietary Chlorella vulgaris(chlorella) intake would be effective on cadmium(Cd) detoxification in rats fed dietary Cd. Fourteen-week old male Sprague-Dawley(SD) rats weighing $415.0{\pm}1.6\;g$ were randomly divided into two groups and fed slightly modified American Institute of Nutrition-93 Growing(AIN-93G) diet without(n=10) or with(n=40) dietary Cd(200 ppm) for 8 weeks. To confirm alteration by dietary Cd intake, twenty rats fed AIN-93G diet without(n=10) and with(n=10) dietary Cd were sacrificed and compared. Other thirty rats were randomly blocked into three groups and fed slightly modified AIN-93G diets replacing 0 (n=10), 5 (n=10) or 10% (n=10) chlorella of total kg diet for 4 weeks. Daily food intake, body weight change, body weight gain/calorie intake, organ weight (liver, spleen, and kidney), perirenal fat pad and epididymal fat pad weights were measured. To examine Cd detoxification, urinary Cd excretion and metallothonein (MT) concentrations in kidney and intestine were measured. Food intake, calorie intake, body weight change, body weight gain/calorie intake, organ weight and fat pad weights were decreased by dietary Cd intake. Urinary Cd excretion and MT concentrations in kidney and small intestine were increased by dietary Cd. After given Cd containing diet, food intake, calorie intake, body weight change, body weight gain/calorie intake, organ weights and fat pad weights were not influenced by dietary chlorella intake. Renal MT synthesis tended to be higher in a dose-dependent manner, but not significantly. And chlorella intake did not significantly facilitate renal and intestinal MT synthesis and urinary Cd excretion. These findings suggest that, after stopping cadmium supply, chlorella supplementation, regardless of its percentage, might not improve cadmium detoxification from the body in growing rats.

• Clinical and Experimental Reproductive Medicine
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• v.39 no.1
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• pp.15-21
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• 2012

Objective: Tributyltin (TBT), an endocrine disrupting chemical, has been reported to decrease ovarian function by causing apoptosis in the ovary, but the mechanism is not fully understood. Therefore, we examined whether TBT increases the expression of adipogenesis-related genes in the ovary and the increased expression of these genes is associated with apoptosis induction. Methods: Three-week-old Sprague-Dawley rats were orally administered TBT (1 or 10 mg/kg body weight) or sesame oil as a control for 7 days. The ovaries were obtained and weighed on day 8, and then they were fixed for terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) or frozen for RNA extraction. Using the total RNA of the ovaries, adipogenesis- and apoptosis-related genes were analyzed by real-time polymerase chain reaction (PCR). Results: The ovarian weight was significantly decreased in rats administered 10 mg/kg TBT compared to that in control rats. As determined by the TUNEL assay, the number of apoptotic follicles in ovary was significantly increased in rats administered 10 mg/kg TBT. The real-time PCR results showed that the expression of adipogenesis-related genes such as $PPAR{\gamma}$, ${\alpha}P2$, CD36, and PEPCK was increased after TBT administration. In addition, apoptosis-related genes such as $TNF{\alpha}$ and TNFR1 were expressed more in the TBT-administered rats compared with the control rats. Conclusion: The present study demonstrates that TBT induces the expression of adipogenesis- and apoptosis-related genes in the ovary leading to apoptosis in the ovarian follicles. These results suggest that the increased expression of adipogenesis-related genes in the ovary by TBT exposure might induce apoptosis resulting in a loss of ovarian function.

• Safety and Health at Work
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• v.3 no.3
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• pp.224-234
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• 2012

Objectives: This study was conducted in order to obtain information concerning the health hazards that may result from a 13 week inhalation exposure of n-pentane in Sprague-Dawley rats. Methods: This study was conducted in accordance with the Organization for Economic Co-operation and Development (OECD) guidelines for the testing of chemicals No. 413 'Subchronic inhalation toxicity: 90-day study (as revised in 2009)'. The rats were divided into 4 groups (10 male and 10 female rats in each group), and were exposed to 0, 340, 1,530, and 6,885 ppm n-pentane in each exposure chamber for 6 hour/day, 5 days/week, for 13 weeks. All of the rats were sacrificed at the end of the treatment period. During the test period, clinical signs, mortality, body weights, food consumption, ophthalmoscopy, locomotion activity, urinalysis, hematology, serum biochemistry, gross findings, organ weights, and histopathology were assessed. Results: During the period of testing, there were no treatment related effects on the clinical findings, body weight, food consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross findings, relative organ weight, and histopathological findings. Conclusion: The no-observable-adverse-effect level (NOAEL) of n-pentane is evaluated as being more than 6,885 ppm (20.3 mg/L) in both male and female rats. n-pentane was not a classified specific target organ toxicity in the globally harmonized classification system (GHS).