• Journal of Pharmacopuncture
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• v.18 no.3
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• pp.49-56
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• 2015

Objectives: Anaphylactic shock can be fatal to people who become hypersensitive when bee venom pharmacopuncture (BVP) is used. Thus, sweet bee venom (SBV) was developed to reduce these allergic responses. SBV is almost pure melittin, and SBV has been reported to have fewer allergic responses than BVP. BVP has been administered only into acupoints or intramuscularly, but we thought that intravenous injection might be possible if SBV were shown to be a safe medium. The aim of this study is to evaluate the intravenous injection toxicity of SBV through a single-dose test in Sprague-Dawley (SD) rats. Methods: Male and female 6-week-old SD rats were injected intravenously with SBV (high dosage: 1.0 mL/animal; medium dosage: 0.5 mL/animal; low dosage: 0.1 mL/animal). Normal saline was injected into the control group in a similar method. We conducted clinical observations, body weight measurements, and hematology, biochemistry, and histological observations. Results: No death was observed in any of the experimental groups. Hyperemia was observed in the high and the medium dosage groups on the injection day, but from next day, no general symptoms were observed in any of the experimental groups. No significant changes due to intravenous SBV injection were observed in the weights, in the hematology, biochemistry, and histological observations, and in the local tolerance tests. Conclusion: The results of this study confirm that the lethal dose of SBV is over 1.0 mL/animal in SD rats and that the intravenous injection of SBV is safe in SD rats.

• Journal of Pharmacopuncture
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• v.19 no.3
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• pp.231-238
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• 2016

Objectives: This study used repeated intravenous injections of Saeng Maek San (SMS) injection in Sprague-Dawley (SD) rats to assess the toxicity and the stability of SMS. Methods: Six-week-old male and female SD rats reared by Orient bio Inc were chosen for this pilot study. They were randomly split into four groups: Group 1 (G1), the control group (0.3 mL of normal saline solution/day/animal), and Groups 2, 3 and 4 (G2, G3 and G4), the experimental groups (0.1, 0.2 and 0.3 mL/day/animal of SMS), respectively. Each animal received an intravenous injection of SMS once a day for four weeks. Clinical signs, body weight changes, and food consumption were monitored during the observation period, and urinalysis and hematology were conducted after four weeks of SMS or saline administration. Results: No deaths occurred in any of the four groups during the observation period. Compared to the control group, male and female rats in groups 3 and 4 (0.2 and 0.3 mL/animal/day) showed hemoglobinuria, but the low-dosage group (G2, 0.1 mL/animal/day) showed no significant changes in the clinical signs test. No significant changes due to SMS were observed in the experimental groups regarding body weight changes, food consumption urinalysis, or hematology. Conclusion: During this study, no mortalities were observed in any of the experimental groups and no hemoglobinuria was observed in the low dosage group (0.1 mL/animal/day) while it was intermittently observed in groups 3 and 4 (0.2 and 0.3 mL/animal/day). Thus, we suggest that the no-observed adverse-effect level (NOAEL) is 0.1 mL/animal/day in male and female SD rats.

• Journal of Pharmacopuncture
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• v.18 no.2
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• pp.60-66
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• 2015

Objectives: This study was carried out in order to find both the single-dose intramuscular injection toxicity and the approximate lethal dose of samjeong pharmacopuncture (SP) in Sprague-Dawley (SD) rats. Methods: The SD rats in this study were divided into four groups, one control group (1.0 mL/animal, normal saline) and three experimental groups (0.25, 0.5, and 1.0 mL/animal, SP). All groups consisted of five male and five female rats. SP was injected as a single-dose intramuscularly at the thigh. After the injection, general symptoms and weight were observed for 14 days. After the observations had ended, hematologic and serum biochemical examinations, necropsy and a local tolerance test at the injection site were performed. The experiments were carried out at the Good Laboratory Practice firm, Biotoxtech Co. (Cheongwon, Chungbuk). Animal experiments were approved by the Ethics Committee (Approval Number: 130379). Results: No deaths occurred in any of the three experimental groups. The injection of SP had no effects on the general symptoms, body weights, results of the hematologic, and serum biochemical examinations, and necropsy findings. In local tolerance tests at the injection sites, mild inflammation was observed in the experimental group, but it did not appear to be a treatment related effect. Conclusion: Under the conditions of this test, the results from the injection of SP suggest that the approximate lethal dose of SP is above 1.0 mL/animal for both male and female SD rats. Therefore, the clinical use of SP is thought to be safe.

• The Korean Journal of Zoology
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• v.18 no.3
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• pp.147-156
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• 1975

In order to determine the influence of low atmospheric pressure on serum glutamic oxaloacetic transaminase (SGOT) and serum lactic dehydrogenase (SLDH) activities of rats, blood samples were collected from laboratory-conditioned male rats of the Sprague-Dawley strain which were randomly grouped into control and the experimental subjected to a series of one hour-exposure a day to low atmospheric pressure of 500 and 380mmHg up to the the time of 15 day. Results obtained indicated that decompression caused marked alterations in SGOT and SLDH levels when compared to that of the control. The trend of increases or decreases in these enzyme levels were similar in both 500 and 380mmHg exposed rats although the changes were greater in the latter group. Thus, generally all the experimental rats showed temporary steady state to low atmospheric pressure. Changes in enzymatic contents depended on the intensity and extent of the environmental stress under study. The lower the atmospheric pressure the greater is the effect on these serum enzyme levels.

• Korean Journal of Exercise Nutrition
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• v.13 no.2
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• pp.155-160
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• 2009

PURPOSE. The purpose of this study was to investigate the effects of fasting and high-fat diet feeding on uncoupling protein 3 (UCP3) mRNA levels, uncoupling the respiratory chain and producing heat, of skeletal muscle in rat. METHODS. Fasting experiment: Forty Male Sprague-Dawley rats (5 wk) were divided into non-fasting groups (CON) and fasting groups (FG) for 0 day, 0.5 day (12 hr), 1 day, 2 day and 3 day. The rats of CON were sacrificed at 0 and 3 day. High-fat diet experiment: Forty Male Sprague-Dawley rats (5 wk) were divided into low-fat diet groups (LF) and high-fat diet group feeding for 0 day, 0.5 day (12 hr), 1 day, 2 day and 3 day. The rats of LF were sacrificed at 0 and 3 day. Analysis: Analysis of UCP3 mRNA expression was used by Real-time PCR. RESULTS. UCP3 mRNA levels of FG group were increased according to time course for 2 days- fasting but decreased at 3 day-fasting. UCP3 mRNA of HF were increased during HF diet feeding for 2 day, and peaked at 1 day-HF feeding, but decreased 2 day and 3 day-HF feeding CONCLUSION. Therefore, it may be rational that UCP3 is up-regulation when a large amount of fatty acids influx occurs in skeletal muscles as well as might have a role for fine adjustments of energy expenditure.

• Toxicological Research
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• v.23 no.1
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• pp.87-96
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• 2007

Single and repeated-dose toxicity of anti-diabetic herb extract microcapsule (ADHEM) were evaluated according to Toxicity Test Guidelines of Korea Food and Drug Administration using Sprague-Dawley rats. For single-dose toxicity test, kneading ADHEM with sterilized water were administered orally once at dose levels of 0 and 2,000 mg/kg and examined for 14 days. No dead animals, clinical signs and abnormal necropsy findings were observed and also no significant difference in body weights was found. Therefore, the $LD_{50}$ of ADHEM was considered to be higher than 2,000 mg/kg in both male and female rats. For repeated-dose toxicity test, ADHEM were mixed with powder fodder and administerd orally for 28 days at dose levels of 0, 500, 1000 and 2000 mg/kg/day. No dead animals, clinical signs and significant difference in body weights were found. In hematology and serum biochemistry, all values were included within the normal ranges. In relative organ weights, kidney or liver were significantly increased in the 500, 1000 or 2000 mg/kg/day male groups, uterus was significantly increased in the 500 mg/kg/day female group and left adrenal glands were significantly decreased in the 2000 mg/kg/day female group. In histopathological examinations, vacuolation and microgranuloma in the liver, chronic progressive nephropathy and inflammation in the kidney were observed in the 500, 1000 or 2000 mg/kg/day both male and female groups. Therefore, the no observed adverse effect level (NOAEL) of ADHEM was considered to be lower than 500 mg/kg/day in both male and female rats.

• Journal of Nutrition and Health
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• v.32 no.6
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• pp.644-653
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• 1999

Background : Excessive intakes of $\omega$6 polyunsaturated fatty acid (PUFA) can increase oxidative stress, which may increase insulin resistance and could be the cause of metabolic syndrome X such as diabetes mellitus. One of the ways to reduce oxidative stress is the consumption of antioxidants such as vitamin E. It is controversial that vitamin E intakes may alleviate insulin resistance. The purpose of the study was whether high vitamin E intake may influence whole body glucose disposal rate(GDR), glycogen deposites, triglyceride content, lipid peroxide levels and antioxidant enzyme activities in Sprague Dawley rats fed high $\omega$6 PUFA diest. Methods : Sprague Dawley rats were divided into three groups. The control group consumed chow diet. High and low vitamin E groups consumed 40% PUFA of total energy intakes. One kilogram of diet mixture contained 300IU of $\alpha$-tocopherol in high vitamin E group, while it had 30 IU in low vitamin E group. Diets were given for 8 weeks. After 7 were of diet consumption, indwelling catheters were inserted in carotid artery and jugular vein of all rats so that GDR could be measured in awake and unstressed state. Results : Daily PUFA intakes were lower in the control group than others. Daily vitamin E intake of high vitamin E group was about ten times higher than those of low vitamin E group and the control group(p<0.0001). $\alpha$-tocopherol content in lier was highest in the high vitamin E group. GDR of the control group was 24% higher than others, and vitamin E intakes did not affect GDR. Glycogen deposit of liver in the control group was significantly higher than others, and it was not altered by vitamin E supplementation. Muscle glycogne content showed a similar tendency as liver glycogen in different diet groups. Triglyceride deposit in muscle was not different among groups. Lipid peroxide content of liver in the high vitamin E group was lower than the low of glutathione peroxidase were lowered in low vitamin E group than others, however, those of superoxide dismutase and catalase were not different. Conclusions : High vitamin E intakes can decrease oxidative stress in rats fed high (())-6 PUFA diet, but they cannot alleviate insulin resistance. Thus, increased oxidative stress through high (())-6 PUFA diet may be minimal for influencing insulin resistance.

• Korean Journal of Veterinary Research
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• v.43 no.4
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• pp.541-549
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• 2003

The present study investigated the effects of aging on Leydig cells of Sprague Dawley rats. Rats of 3, 6, 12 and 18 months of age were used. Testes of rat were fixed by whole body perfusion using a fixative containing 2.5% glutaraldehyde in cacodylate buffer, processed and embedded in epon-araldite. Using $1{\mu}m$ sections stained with methylene blue, qualitative and quantitative morphological studies were performed. Testis incubations were used to determine luteinizing hormone (LH; 100 ng/ml) stimulated testosterone secretory capacity per testis in vitro. Testosterone levels in the incubation medium, and testosterone and luteinizing hormone levels in serum of these four groups of rats were determined by radioimmunoassay. Morphological studies revealed that Leydig cells were more abundant in the testis interstitium at 6, 12 and 18 months when compared with 3 months. The volumes of Leydig cells per testis was significantly higher, at 6, 12 and 18 months of age than those at 3 months. The number of Leydig cells per testis was doubled at 6, 12 and 18 months of age compared with 3 months. The average volume of a Leydig cell was not significantly different between 3 and 6 months of age, however, at 12 and 18 months a significantly lower value was observed. LH-stimulated testosterone production per testis in vitro was reduced by 45% at 6 months of age compared with 3 months; a further significant reduction was observed at 12 and 18 months. Serum testosterone and LH levels were not significantly different between 3 and 6 months of age but at 12 and 18 months a significantly lower value was observed in both groups for these hormones. These results showed that signs of aging are apparent in Leydig cells of Sprague Dawley rats at 12 months of age.

• Journal of the Korean Society of Food Science and Nutrition
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• v.37 no.9
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• pp.1120-1125
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• 2008

This study was carried out to investigate the effects of Sophorae fructus extracts on antioxidative potential, free radical generation and the lipid levels in rats. Sprague-Dawley (SD) rats were divided into 2 groups of either AIN-76 diet (control group) or modified AIN-76 diet with 0.5% Sophorae fructus extracts for 4 weeks. The result were as follows: body weight gain and feed efficiency ratios were not significantly different in both groups. Antioxidative potentials were significantly increased in the group fed Sophorae fructus extracts compared to control group; however, there was no difference in free radical generation. Organ (heart, kidney, liver, spleen) weights in rats were not different in both groups. Total cholesterol level in Sophorae fructus group was significantly decreased compared to control group. Serum HDL-cholesterol level in Sophorae fructus group was significantly higher than control group. Serum phospholipid and triglyceride contents in Sophorae fructus group were no different from control group. These results suggest that supplementation of Sophorae fructus extracts may beneficially contribute to the effects of antioxidative potential and lipid levels in rats.

• Toxicological Research
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• v.26 no.1
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• pp.75-82
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• 2010

This study was carried out to investigate the short term toxicity of nine phthalate diesters including di-2(ethylhexyl) phthalate (DEHP), di(n-butyl) phthalate (DBP), di-n-octyl phthalate (DnOP), diethyl phthalate (DEP), butylbenzyl phthalate (BBP), dimethyl phthalate (DMP), di-isodecyl phthalate (DIDP), diundecyl phthalate (DUP), and di-isononyl phthalate (DINP) and five phthalate monoesters including mono- (2-ethylhexyl) phthalate (MEHP), monobutyl phthalate (MBuP), monobenzyl phthalate (MBeP), monoethyl phthalate (MEP), monomethyl phthalate (MMP) and phthalic acid (PA) in Sprague-Dawley male rats. Animals were administered 250 mg/kg/day (monoesters and PA) or 500 mg/kg/day (diesters) of phthalate for two weeks. All animals were examined for body and organ weights, blood hematology, serum biochemistry, and urine analysis. The body weight gain was significantly lower in rats treated with BBP, DBP, DINP, MEHP, MBuP, and PA than that of control. Liver weights were significantly increased in the DEHP, DBP, DnOP, DIDP, and MEHP groups as compared to the control group. Testes weights were significantly decreased only in the DEHP-, DnOP-, and DIDP-treated groups as compared to the control. Significant differences in hematological changes were not observed in any treatment groups. Significant increases in blood glucose levels were observed in the DEHP, MEHP, and MBeP groups. Aspartate aminotransferase (AST) levels were significantly increased in the DBP, DUP, DINP, MBuP, and MBeP groups, whereas alanine aminotransferase (ALT) levels were significantly increased only in the DEHP and MEHP groups. Serum ALP levels were significantly higher in phthalate diester (500 mg/kg/day)-treated rats as compared to control. However, the total cholesterol level was significantly reduced in the DEHP- and DIDP-treated groups, whereas serum triglyceride (TG) levels were higher in the DINP-, MEHP-, and MBuP-treated groups. These results suggest that short term toxicity of phthalate monoesters produces adverse effects as similar to phthalate diesters in Sprague-Dawley rats.