• Korean Journal of Oriental Medicine
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• v.9 no.2
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• pp.131-148
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• 2003

This study was performed to evaluate the acute oral toxicity of an oriental medical prescription for obesity treatment, SH21-B, in Sprague-Dawley rats and Beagle dogs. SH21-B was administered in rats at does of 0mg/kg, 2,000mg/kg, and 5,000mg/kg. And also SH21-B was administered in Beagle dogs at does of 150mg/kg, 300mg/kg, and 600mg/kg. The rats and dogs of both sexes were observed daily for 14 days after single oral administration. Two female rats, one administered at 2,000mg/kg and the other administered at 5,000mg/kg, died, but no dead animal was observed among male rats. Therefore LD50 in the female rat is observed to be 8,710mg/kg, and MLD(Minimum Lethal Dose) of the male rat is observed to be more than 5,000mg/kg. Among dogs, no dead animal was observed up to 600mg/kg and MLD is observed to be more than 600mg/kg.

• Journal of the Korean Society of Food Science and Nutrition
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• v.27 no.5
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• pp.973-979
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• 1998

This study was conducted to investigate the effectiveness of pumpkin powder in the diet of experimental animals on chemically induced stomach and mammary canceers. Three weeks old male SpragueDawley rats were randomly allocated to either 1) basal diet+MNNG, 2) basal diet+MNNG+PMC, 3) 2.5% pumpkin powder supplemented diet+MNNG+PMC, or 4) 5.0% pumpkin powder supplemented diet+MNNG+PMC for stomach cancer experiment. And female Sprague-Dawley(5 weeks old) rats were randomly assigned to either 1) basal diet only, 2) basal diet+DMBA, 3) 2.5% pumpkin powder supplemented diet+DMBA, or 4) 5.0% pumpkin powder supplementd diet+DMBA. In both experiments, supplements of pumpkin powder in basal diet decreased body weight of both male and female experimental animals. Pumpkin powder in rat diet decreased significantly(p<.05) chemically induced stomach cancer. With its suppressing effects on stomach cancer, pumpkin powder in diet of experimental rats had decreasing effects on the initiation and development of DMBA-induced mammary cancer. In conclusiion, current study may provide in vivo data to develop health foods using pumpkin. Further studies, however, are essential to clarify the exact role of pumpkin powder in chemically induced stomach and mammary cancers.

• The Journal of Korean Medicine
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• v.30 no.5
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• pp.102-114
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• 2009

Objectives: HMCO5 is an extract obtained from 8 different herbal mixtures. We undertook a safety evaluation of HMCO5 for a dose range finding (DRF) toxicity test in specific pathogen free (SPF) Sprague-Dawley (SD) male and female rats. Methods: The male and female rats were divided into 4 groups, respectively; G(0), treated with distilled water: G(1), treated with 222 mg/kg HMC05: G(2), treated with 667 mg/kg HMC05, and G(3), treated with 2,000 mg/kg HMC05; HMC05 was administered orally for 4 weeks. The safety evaluation examined clinical signs, mortality, body weight, food consumption, water consumption, ophthalmic findings, urinalysis, hematological values, absolute & relative organ weights, and necropsy findings during the tests. Results: There were no changes in clinical signs, mortality, body weight, food consumption, water consumption, and ophthalmic findings examined during the test periods. In serum biochemical values, triglyceride was increased in male group G(3) and Na$^+$ decreased significantly in male groups G(2), G(3) and G(4). In male group G(4), spleen weight decreased relatively and increases of absolute & relative left ovary weights were found. In addition, an adhesion of liver to diaphragm was found in male group G(2). However, we could not find any dose-interrelationships in these changes. Conclusions: These results indicate that HMC05 extract did not show any toxicity in the DRF toxicity study. Therefore, it suggests that establishment of 1,000, 333 and 111 mg/kg dosages are moderate in a repeated dose 26-week oral toxicity study of HMC05.

• Environmental Analysis Health and Toxicology
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• v.21 no.3 s.54
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• pp.291-299
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• 2006

The experiments investigated whether early exposure to testosterone propionate (TP) during prepuberty alters testis development in Sprague-Dawley male rats. We performed Hershberger assay using the stimulated weanling male rats by OECD protocols, cDNA microarray, and Western blot. TP was subcutaneously injected to uncastrated Sprague-Dawley male rat of 22 days old for 10 consecutive days at doses of 0.4, 0.8, 1.0, 1.2, 1.6 mg/kg per day. At necropsy, the following tissues were removed and weighed: combined testes, epididymides (Epi), Cowper's glands (COW), levator am, and bulbocavernosus muscles (LABC), seminal vesicles, together with coagulating gland (SV) and ventral prostate (VP). We found that TP increased the weights of Epi, VP, SV, COW, and LABC, while testis was decreased in a dose-dependent manner. In cDNA microarray analysis of testis, there were significant reductions in the expression of cytochrome P450 11A (CYP11A), the rate-limiting enzyme of steroidogenesis. Taken together these results, TP exposure before puberty in male rats may produce the delay in testis development by inhibiting the CYP11A gene expression.

• The Journal of Pediatrics of Korean Medicine
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• v.16 no.1
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• pp.149-169
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• 2002

This study was designed to observe the efficacy of Boyangsengjang-Tang(BST) on the growth of rats. The effects on growth, and the secretion of hormones in the serum was measure. Male BALA/C mice(weight 20-25g), and male ICR rats(weigh 120-150g), were each divided into 3 groups : Sample A, Sample B and a Control group. Each group consisted of 4 mice and 5 rats. Mice received $5{\mu}{\ell}$ BST, and rats received $50{\mu}{\ell}$ BST, daily. Sample A was administered with normal BST for 3 weeks. Sample B was was administered with 10 times the normal amount of BST for 3 weeks. Control group was administered with normal saline for 3 weeks. The body weight, body length, subcutaneous fat, length of femur, serum GH, serum IGFBP-3 and serum in TSH were measured at 1, 2, and 3 weeks. The results were as follows ; 1. The body weigh of the rats increased significantly in Sample A after 3 weeks when compared with control group. 2. The body length in rats increased significantly in Sample A when compared with control group. 3. The amount of subcutaneous fat in the mice increased significantly in Sample B after 1 week when compared with control group. The amount of subcutaneous fat in rats increased significantly in Sample A and Sample B after 3 weeks when compared with the control group. 4. The length of the femur in rats increased significantly in Sample in A and Sample B in 1, 2, and 3 weeks when compared with the control group. 5. The level of GH, IGFBP-3 and TSH in the serum was not statically different when compared with the control group. According to the above results, BST (which reinforces the Kidney's Yang and strengthens muscle and bone) increases body weight, body length, subcutaneous fat and the length of the femur when compaired with the control group. BST therefore seems to improve growth.

• Biomolecules & Therapeutics
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• v.8 no.1
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• pp.84-92
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• 2000

This Study was conducted to assess the single dose toxicity of DA-125, a new anthracycline anti-cancer agent, in rats and mice. The Drug was administered once intravenously to both sexes of rats and mice. Then followed a 14-day period of observation. The $LD_{50}$ Values (95% confidence limit) were estimated to be 60.9 mg/kg (57.5~64.3 mg/kg) for male rats and 60.2 mg/kg (56.2~64.5 mg/kg) for female rats, and 85.8 mg/kg (81.0~90.9 mg/kg) for male mice and 84.5 mg/kg (78.2~91.9 mg/kg) for female mice. Both sexes of rats and mice given the drug revealed the clinical sign of decreased locomotor activity, emaciation, hair loss, red-dish brown urine, salivation, and watery diarrhea. In addition, body weight from the next day to the 7th day tended to be decreased slightly in rats and mice treated with DA-125. Death occurred from the next day after administration to the 12th day. Macroscopically, congestion of gastrointestinal organ, lung, and adrenal glands were found in both sexes on the dead rats and mice. Histopathological examination of dead rats manifested atrophy of spleen, hypoplasia of bone marrow, hypcplasia and necrosis of lymphocyte in thymus, atrophy of villi in small intestine (duodenum, jejunum, and ileum), hyperplasia of granular epithelium in small intestine, degeneration of germinal epithelium in testis, defer oration of tubular epithelium in kidney, and vacuolation and myolysis of myocardium in heart. Histopathological examination of dead mice revealed hypoplasia of spleen and mesenteric lymph node, local necrosis of liver, atrophy of villi in small intestine, hyperplasia of glandular epithelium in small and large intestine, degeneration of tubular in kidney, degeneration of germinal cells in testis, and slight vacuolar degeneration of myocardium in heart.

• Archives of Pharmacal Research
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• v.27 no.5
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• pp.547-553
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• 2004

The pyrrolizidine alkaloids (PAs), contained in a number of traditional remedies in Africa and Asia, show wide variations in metabolism between animal species but little work has been done to investigate differences between animal strains. The metabolism of the PA senecionine (SN) in Fischer 344 (F344) rats has been studied in order to compare to that found in the previously investigated Sprague-Dawley (SO) rats (Drug Metab. Dispos. 17: 387, 1989). There was no difference in the formation of ($\pm$) 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP, bioactivation) by hepatic microsomes from either sex of SO and F344 rats. However, hepatic microsomes from male and female F344 rats had greater activity in the Noxidation (detoxication) of SN by 88% and 180%, respectively, when compared to that of male and female SD rats. Experiments conducted at various pH showed an optimum pH of 8.5, the optimal pH for flavin-containing monooxygenase (FMO), for SN N-oxidation by hepatic microsomes from F344 females. In F344 males, however, a bimodal pattern was obtained with activity peaks at pH 7.6 and 8.5 reflecting the possible involvement of both cytochrome P450 (CYP) and FMO. Use of specific inhibitors (SKF525A, 1-benzylimidazole and methimazole) showed that the N-oxide of SN was primarily produced by FMO in both sexes of F344 rats. In contrast, SN N-oxide formation is known to be catalyzed mainly by CYP2C11 rather than FMO in SD rats. This study, therefore, demonstrated that there were substantial differences in the formation of SN N-oxide by hepatic microsomes from F344 and SD rats and that this detoxification is catalyzed primarily by two different enzymes in the two rat strains. These findings suggest that significant variations in PA biotransformation can exist between different animal strains.

• Toxicological Research
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• v.14 no.4
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• pp.547-555
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• 1998

The subchronic toxicity of a combined preparation of ticlopidine and ginkgo biloba extract (EGb 761) mixed in a ratio of 10: 4 was examined in male and female Sprague-Dawley rats. Rats were treated with the test substance at a dose of 52 mg/kg, 156 mg/kg, or 467 mg/kg intragastrically for 30 consecutive days. Control rats were treated with vehicle only. Each group consisted of 10 rats. No death or abnormal clinical signs were observed throughout the administration period. A transient decrease in body weight gain and food intake was observed in the rats treated with the high dose (467 mg/kg), which was recovered to normal in a week. There were no drug-related differences in urinalysis and hematological results. A significant increase in serum total cholesterol and total protein was observed in both sexes of the rats treated with a dose of 467 mg/kg daily, but all the other values obtained in serum chemistry appeared to be within normal range. A dose dependent increase in liver weight was observed in both male and female rats. Relative kidney weight was also increased in the high dose groups. There was no gross pathological finding at terminal sacrifice. Microscopic histopathological examination did not show any lesion in terms of correlation with administration of the test substance. The results suggest that under the conditions employed in this study no observable effect level (NOEL) of the test substance be 52 mg/kg/day.

• Journal of Nutrition and Health
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• v.25 no.5
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• pp.397-403
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• 1992

This study was performed to investigate the effect of dietary magenesium on stress reactions in rats having abdominal surgery. Sixty three male rats of sprague-dawley strain were blocked into 3 groups : rats fed regular magnesium (0.05% Mg: control) rats receiving regular magnesium with surgery(Mg-adeq : S) Five weeks after feeding abdominal surgery was performed and randomly chosen 7 rats from each group were sacrificed on 1, 3 and 5 days after surgery. Te following were found ; 1) Rats fed marginal magnesium showed significantly elevated urinary urea nitrogen urinary potassium and plasma glucose compared controls only one day after abdominal surgery but not 3 days or 5 days after surgery 2) Rats fed adequate magnesium did not show any significant change in metabolic stress indicator after surgery. 3) Plasma free fatty acid and cortisol level were not different among groups. 4) Decreased plasma magnesium and potassium level were found in rats fed marginal magne-sium and sacrificed one day and three days after surgery.

• Journal of Nutrition and Health
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• v.38 no.2
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• pp.89-95
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• 2005

This study was performed to investigate the effect of soy isoflavone on plasma nitrite concentration and the antioxidant enzyme activities of erythrocyte and the liver using adult male rats fed high fat diet. Seven-week old male Sprague Dawley rats were divided into three groups and fed high fat diet (15% beef tallow, 1 % cholesterol; control: IF0) or high fat diets containing isoflavone 80 ppm (IF80) or 320 ppm (IF320) for 10 weeks. Plasma nitrite concentration as a vasodilator, and antioxidant enzyme activities in erythrocytes and the liver were measured. Plasma nitrite concentration was increased by 45% and 35%, respectively, in IF80 and IF320 than in IF0 group. Erythrocyte catalase, glutathione peroxidase (GPx) and glutathione reductase (GR) activities increased by 31 %, 30% and 40% in IF320 compared to IF0 group. Especially, erythrocyte GR activity increased by 61 % in IF80 group. However, catalase activity in the liver was decreased in IF80 group. GPx and GR activities in the liver were not differ among groups. The results suggest that soy isoflavone have the protective effect against risk factors related with cardiovascular disease by improving vasodilator factor, nitrite, and antioxidant enzyme activities in blood. (Korean J Nutrition 38(2): 89～95, 2005)