This study was designed to evaluate a repeated oral dose toxicity and immunomodulating activity of Pulsatilla koreana and Artemisiae annuae in Sprague-Dawley rats. The female rats were treated with Pulsatilla koreana and Artemisiae annuae of control group, low group (0.5 ml/kg), medium group (1 ml/kg), high group (2 ml/ kg) for distilled water, intragastrically for 4 weeks, respectively. To ensure the safety of Pulsatilla koreana and Artemisiae annuae such as the following were observed and tested. We examined the body weight, the feed intake, the clinical signs, the ophthalmological test, the hematological and the serum biochemical analysis. We also observed the histopathological changes of liver and kidney in rats. Hematological results were the increase of neutrophils, lymphocytes and monocytes in the high dose group of Pulsatilla koreana. The increase immune cells in the high dose group of Pulsatilla koreana might immunomodulating activity. No significant differences in body weight, feed intake, serum biochemical analysis and histopathological between control and fed group were found. In conclusion, Pulsatilla koreana and Artemisiae annuae is physiologically safe and improve immunomodulating activity.

This study was carried out to investigate the toxicity of food Red No.2 in the Sprague-Dawley (SD) female rat for 4 weeks. SD rats were orally administered for 28 days, with dosage of 500, 1,000, 2,000 mg/kg/day. Animals treated with food Red No.2 did not cause any death and show any clinical signs. They did not show any significant changes of body weight, feed uptake and water consumption. There were not significantly different from the control group in urinalysis, hematological, serum biochemical value and histopathological examination. In conclusion, 4 weeks of the repetitive oral medication of food Red No.2 has resulted no alteration of toxicity according to the test materials in the group of female rats with injection of 2,000 mg/kg. Therefore, food Red No.2 was not indicated to have any toxic effect in the SD rats, when it was orally administered below the dosage 2,000 mg/kg/day for 4 weeks.

This study was conducted to examine the effect of 3,3',4,4',5-pentachlorobiphenyl (PCB 126) on morphological changes in the developing rat testis. PCB 126 (0.2㎎/㎏/week) in corn oil was weekly i.p. injected into rats from 1 to 11 weeks old. The total body weights and testicular weights were measured at 3, 6, 9 and 12 weeks, respectively. The morphological changes in the rat testes were then analyzed by light microscopy (LM) and transmission electron microscopy (TEM). The results demonstrated that PCB 126 treatment caused significant change in the ratio of testicular weight/body weight at 9 week. The treatment of PCB increased the number of pregonium cells at 3 week and it decreased spermatogenesis of the seminiferous tubules at 6 week. The results of this study suggest that PCB 126 can damage the male reproductive organ of the growing rat and that it might be associated with retardation of development of the testis.

Plantago asiatica L. (P. asiatica) has been used as one of the popular folk medicines in Asia for human health care practices. Various activities of P. asiatica have been reported, such as anti-oxidant, anti-glycation,anti-inflammatory and hepatoprotective activity. Therefore, the potential of P. asiatica to reduce oxidative stress has been studied in several ways for over 20 years, especially at liver and kidney. However no investigation has been reported revealing its protective effect on prostate. Method : Treatment of P. asiatica leaf ethanolic extract (PLE) (1 g/kg body weight (b.w.), 2 g/kg b.w., or 4 g/kg b.w.) were given separately to animals for pretreatment once per day for 7days, and on the seventh day ferric nitrilotriacetate (Fe-NTA; 0.24 mmol Fe/kg b.w.), which is known as an oxidative stress-inducer at prostate, was administrated by i.p to negative control group. At the end of the study period, dissection was carried out for detecting the prostate protective effect of PLE. Result : Fe-NTA-treated animals produced reactive oxygen species (ROS) resulting in depletion of antioxidant biomaker, such as glutathione (GSH), glutathione reductase (GR), and glutathione s-transferase (GST) and increase of lipid peroxidation in prostate. However, PLE pretreatment resulted in an increase in the GSH, GST and GR levels concentration dependent manner and in an significant decrease in the levels of lipid peroxidation. Conclusion : Our data suggest that PLE may be effective in protecting oxidative stress-induced damage of prostate, and PLE may be an chemopreventive agent against Fe-NTA-mediated prostate oxidative damage.

Plantago asiatica L. (PA), which is widely distributed in Korea, Japan and China, has traditionally been used as a popular folk medicine for the treatment of liver diseases. A variety of activities of PA was reported, that is hepatoprotective, anti-inflammatory, anti-glycation and anti-oxidant effect. Ferric nitrilotriacetate (Fe-NTA) is a potent nephrotoxic agent and has been reported to induce renal proximal tubular necrosis. In the present study, pretreatment with PA extract (PAE) in Wistar rat followed by Fe-NTA i.p. treatment (13.5 mg Fe/kg body weight) was performed to detect the renal protective effect of PAE. Only Fe-NTA treated group showed increases in the level of serum blood urea nitrogen (BUN) and serum creatinine (Cr), and renal tissue malondialdehyde (MDA), product of lipid peroxidation. Moreover, the level of biomarkers indicate the antioxidants status, reduced glutathione (GSH), glutathione-S-transferase (GST) and glutathione reductase (GR) were decreased. However, PAE pre-treated group showed decreases in the levels of serum BUN, serum Cr and renal tissue MDA in concentration dependent manner and increases in the level of GSH, GST and GR. These results are significantly different (p < 0.05) to the other groups. Our data suggest that PAE may be used as an chemopreventive material against Fe-NTA-mediated renal oxidative stress.

To investigate the toxicological effects of β-glucan, we performed basic studying on β-glucan in Sprague-Dawley (SD) rats. Standard endpoints in this study included mortality, clinical observations, changes of body weights, analysis on food consumption, ophthalmoscopic examination, hematologic examination, serum biochemistry,analysis of organ weights, gross anatomic pathology and histopathology. No clinical signs and mortality were observed in animals treated with beta-glucan throughout the experimental period. The average body weight of each treatment groups showed similar levels at end of experiment. There were no treatment-related changes in mortality,body weights changes, food consumption, ophthalmoscopic examination. Although there were statistically significant differences between the control and treated groups in some relative and absolute organ weights, and hematological and biochemical analysis, the data were in biologically normal ranges and did not show a dose-dependent manner. In the morphological change, hepatic tissue were not showed ballooning degeneration and irregular arrangement of hepatic cell in β-glucan treatment groups with control group. Also, organs weights (liver, heart, kidney and stomach) and hematological indices (WBC, RBC, Hb, Hct and Platelet) did not show statistically significant differences among the experimental groups. In summary of these results, there were no changes in mortality, mean body weight, clinical signs, food consumption. There were no changes in ophthalmological examination, hematology, blood chemistry,necropsy and histopathology. In conclusion, although further investigation of glucan should be performed in the functions registered in many ancient literatures, β-glucan is physiologically safe and may have potential as candidate food for human health.

본 연구는 8주령 Sprague-Dawley계통의 암컷 랫드에서 제독유황을 반복경구투여 독성평가를 하기위해 시행하였다. 랫드에 처치한 물질은 사료섭취량의 0.2%, 1%, 5% 제독유황과 사료섭취량의 1% 유황으로 13주 경구투여를 하였다. 제독유황의 안전성을 확인하기 위해 다음과 같은 관찰 및 검사를 하였다. 검사항목으로는 체중과 사료 섭취를 측정하였고 임상증상, 안과학적 검사, 혈액학적 검사, 혈청 생화학적 검사를 관찰하였다. 또한 랫드에 간과 신장에서 의 병리조직학적 변화를 관찰하였다. 그 결과 체중, 사료섭 취량, 혈액학적 및 병리조직검사 소견에서 대조군과 제독 유황 그룹 간의 유의적인 차이가 보이지 않았다. 혈청생화 학적 검사소견에서는 0.2% 및 1% 투여군에서는 대조군과 비교시 용량의존적으로 유의적인 차이를 보이는 항목은 보이지 않았으나, 고용량군에서는 glucose 감소에 의한 저칼 륨혈증, 인슐린 과잉분비의 독성을 의심할 수 있었으며, 또 한 ALT와 ALP의 증가는 간 독성이나 간암, 황달의 유발이 의심되었다. 한편, 병리조직학적인 검사에서는 시험 전체군에서 대조군과 비교시 유의할만한 병리조직이상이 관 찰되지 않았다. 따라서 본 연구에서는 사료섭취량 1%의 제독유황까지 투여는 랫드에서 독성을 나타내지 않는 것으로 사료된다.

This study was performed to investigate the effect of dried powder of chestnut on lipid metabolism, anti-thrombotic effect in rats. Thirty 5-week-old male Sprague Dawley (SD) rats were randomly allocated into five groups and used for experiment. We examined the lipid metabolism and antithrombotic capacity of SD rats administered for 5 weeks with 0.16 g/kg, 0.5 g/kg chestnut flesh powder and 0.16 g/kg, 0.5 g/kg chestnut inner shell and flesh powder mixture, respectively. Food intake, body weight gain and food efficiency ratio were also checked. The levels of serum triglyceride and free fatty acid were not statistically significant between the all experimental groups. However, the antithrombotic capacity and total lipid levels of the treatment groups were significantly lower than those of the negative control group. These results suggest that the supplementation of chestnut on diet lower the total lipid level in SD rats.

Four-week repeated-dose toxicity of Misaengtang (MST) was evaluated according to Toxicity Test Guideline of Korea Food and Drug Administration using 6-week-old Sprague-Dawley rats. Based on the results of preliminary single-dose toxicity study, confirming safety up to an upper-limit dose, MST was dissolved in drinking water and orally administered at doses of 500, 1,000, or 2,000 mg/kg for 28 days. All doses including the upper-limit limited dose (2,000 mg/kg) of MST did not cause any abnormalities of rats, including mortality, clinical signs, body weight gain, feed/water consumption, necropsy findings, organ weights, hematology and blood biochemistry. Rather, high doses (1,000-2,000 mg/kg) of MST reduced the serum levels of alanine transaminase, aspartate transaminase, creatinine phosphokinase, lactate dehydrogenase and triglycerides, in addition to an increase in glucose, indicative of protective effects on hepatic and muscular injuries. Both maximum-tolerable dose and no-observed-adverse-effect level were not determined. The results indicate that long-term intake of high-dose MST might not induce general adverse-effects.

본 연구는 항암, 항균, 항산화 등의 기능을 나타내는 식물성 플라보노이드인 naringin이 암컷 SD rat의 지질대사와 혈액 생화학적 지표에 미치는 영향을 살펴보기 위해 수행되었다. 실험은 5주령의 암컷 SD rat를 대상으로 일주일에 3번, 총 5주 동안 naringin을 경구투여하여 지질대사와 항혈전능에 미치는 영향을 비교 분석하였으며, 실험군은 대조군(non naringin group), 저용량 naringin 투여군(0.2 g/kg), 고용량 naringin 투여군(0.5 g/kg)으로 구분하였다. 실험결과 랫드의 체중증가량과 상대장기중량에서는 통계학적으로 유의적인 변화가 관찰되지 않았다. 체중증가량에서 3주차 이후에 용량에 비례하지는 않지만 대조군에 비하여 naringin 투여군의 체중 증가율이 적은 것을 관찰 할 수 있었다. 사료섭취량과 체중증가량을 이용하여 각 군의 5주간 식이효율을 구해보았을 때, 군간에 통계학적으로 유의적인 차이는 없었으며, 장기와 조직의 상대장기중량은 간을 비롯하여 신장, 비장 모두 naringin 투여군과 대조군 간에 통계학적으로 유의적인 차이가 없었다. 혈청 중 Triglyceride, free fatty acid, total lipid, glucose의 수치는 대조군에 비해 naringin 투여군에서 유의적으로 감소하였다. 혈청 total cholesterol과 HDL-cholesterol의 수치를 이용한 Atherogenic index 즉, 동맥경화지수는 대조군에 비하여 고용량군이 유의적으로 감소하였다. 항혈전능 실험결과에서는 고용량 naringin 투여군이 대조군에 비해 유의적으로 높은 수치가 관찰되었다. 이상의 결과를 종합해 볼때 암컷 SD rat에서 naringin은 체중감소에 대한 효과는 관찰되지 않았지만, 지질저하 효과, 항산화 효과 등의 면에서 모두 우수하였다. 따라서 우리나라에서 자생하는 천연물 소재에 널리 분포된 naringin은 고혈압과 당뇨병에 효능이 있는 것으로 추측되며 동맥경화에도 효과가 있는 것으로 보여 건강기능 식품 소재로 이용될 수 있는 적절한 물질이라 판단된다.

This study was conducted to analyze the expression pattern of inhibitor of DNA binding proteins (Id)1 and Id2 mRNA on folliculogenesis in rat ovary. The ovaries were obtained from 27 days old Sprague-Dawley rat, fixed, dehydrated, and paraffin embedded. For in situ hybridization, anti-sense and sense Idl and Id2 cRNA probes were prepared and applied to the ovarian section. The ovarian sections were coated with NTB-2 emulsion. After that, the slides were developed and counterstained with hematoxylin and eosin staining. In oocytes, the hybridizational signals of Id1 mRNA were strong in primordial and primary follicles, however, there were no signals in that of atretic or preovulatory follicles. The Id2 mRNA signals were also strong in the oocytes of primordial, primary and secondary follicles. Interestingly, the Id2 mRNA was expressed specifically granulosa cells, but nor in oocyte or theca cells in dominant and preovulatory follicles. Based on these results, Id1 and Id2 mRNA was expressed specifically at follicle stages and follicular tissue and might be closely related with follicle development.

Phytic acid (PA) (Inositol hexaphosphate, IP6) is a naturally occurring polyphosphorylated carbohydrate that is present in substantial amounts in almost all plants and mammalian cells. Recently PA has received much attention for its role in anticancer activity. In the present study, the preventive effects of PA on colon carcinogenesis were investigated. Six-week old Fisher 344 male rats were fed a AIN-93G purified diet and PA (0.5% or 2% PA in water) for 8 weeks. The animals received two (1st and 2nd week) injections of azoxymethane (AOM, 15 mg/kg b.w.) to induce colonic aberrant crypt foci (ACF). After sacrifice, the total numbers of aberrant crypts (AC) and ACF in colonic mucosa were examined after staining with methylene blue. Blood and serum were analyzed with a blood cell differential counter and an automatic serum analyzer. AOM induced the total numbers of 142.3 ± 22.3 ACF/colon and 336.6 ± 55.1 AC/colon. PA at the doses of 0.5 and 2% decreased the numbers of ACF and AC/colon in a dosedependent manner. The numbers of ACF/colon and AC/colon by PA at the dose of 0.5% were 124.4 ± 28.5 and 302.7 ± 67.3, respectively. PA at the dose of 2% significantly decreased the ACF and AC numbers to 109 ± 18.1 and 254.8 ± 50.6, respectively (p < 0.01). Especially, 2% PA significantly reduced the number of large ACF ( ≥ 4 AC/ ACF) from 26.8 ± 6.2 ACF/colon to 15 ± 6.7 ACF/colon (p < 0.01). Although some parameters in blood counts and serum chemistry were changed compared with the control, no specific toxicity was found. These findings suggest that phytic acid can be a chemopreventive agent for colon carcinogenesis resulting from inhibition of the development of ACF in the F344 rat.

포유류에서 옥시토신은 다양한 기능을 가지고 있는 신경뇌하수체 호르몬이다. 옥시토신은 주로 젖의 분비를 일으키고 분만 시 자궁의 수축 및 모성 행동과 관계가 있다. 모성 행동은 스트레스에 의해 억압을 받으며 옥시토신에 의해 촉진된다. 본 연구는 제왕절개의 스트레스와 자궁내 옥시투여에 따른 모성 행동의 변화를 알아보기 위해 수행되었다. 본 실험 결과, 자연 분만 예에서 스트레스를 준 개체와 스트레스를 주지 않은 개체에서 새끼의 생존율을 비교한 결과, 스트레