Velvet antler is widely used as a traditional medicine, and numerous studies have demonstrated its tremendous nutritional and medicinal values including immunity-enhancing effects. This study aimed to investigate different deer velvet extracts (Sample 1: raw extract, Sample 2: dried extract, and Sample 3: freeze-dried extract) for proximate composition, uronic acid, sulfated glycosaminoglycan, sialic acid, collagen levels, and chemical components using ultra-performance liquid chromatography-quadrupole-time-of-light mass spectrometry. In addition, we evaluated the cytotoxic effect of the deer velvet extracts on BV2 microglia, HT22 hippocampal cells, HaCaT keratinocytes, and RAW264.7 macrophages using the cell viability MTT assay. Furthermore, we evaluated acute toxicity of the deer velvet extracts at different doses (0, 500, 1000, and 2000 mg/kg) administered orally to both male and female ICR mice for 14 d (five mice per group). After treatment, we evaluated general toxicity, survival rate, body weight changes, mortality, clinical signs, and necropsy findings in the experimental mice based on OECD guidelines. The results suggested that in vitro treatment with the evaluated extracts had no cytotoxic effect in HaCaT keratinocytes cells, whereas Sample-2 had a cytotoxic effect at 500 and 1000 μg/mL on HT22 hippocampal cells and RAW264.7 macrophages. Sample 3 was also cytotoxic at concentrations of 500 and 1000 μg/mL to RAW264.7 and BV2 microglial cells. However, the mice treated in vivo with the velvet extracts at doses of 500–2000 mg/kg BW showed no clinical signs, mortality, or necropsy findings, indicating that the LD50 is higher than this dosage. These findings indicate that there were no toxicological abnormalities connected with the deer velvet extract treatment in mice. However, further human and animal studies are needed before sufficient safety information is available to justify its use in humans.

In this study, the acute toxicity of Dendropanax morbiferus H.Lév leaf hot-water extracts (DMWE) was examined in male and female ICR mice. Mice were orally administered the DMWE at dose levels of 0, 250, 500, 1,000 and 2,000 mg/kg body weight (BW) for single-dose toxicity test. There were no significant differences in change of BW between control and all DMWE treated-groups. In hematological and blood biochemical analysis, none of the parameters were affected by the DMWE. Similarly, there were no significant effects on markers for liver and kidney functions in all DMWE treated-groups. Since there were no adverse effects of the DMWE in single oral toxicity tests, even at the highest doses, it was concluded that the lethal dose 50 (LD50) of DMWE is estimated at > 2,000 mg/kg BW.

Endocrine-disrupting chemicals found in many commercial products may interfere with the normal functioning of the endocrine system and are unsafe because of their cumulative effect on the human body. However, little is known about the effects of combinations of endocrine-disrupting chemicals in humans. Methoxychlor and bisphenol A are toxic to male reproductive organs. Therefore, we studied the effects of methoxychlor and bisphenol A on male reproductive function. Male mice were divided into four treatment groups: control, 400 mg methoxychlor, 1 mg bisphenol A, and 400 mg methoxychlor + 1 mg bisphenol A/kg/day. Methoxychlor and bisphenol A were dissolved in sesame oil and acetone and administered orally for 4 weeks. After administration, the weight and histological changes in the testicles and epididymis, sperm count and health were observed biochemical tests and whole blood counts were performed. The results showed that the mice in the bisphenol A and methoxychlor + bisphenol A groups gained more weight than those in the control and methoxychlor group. The weights of the testes and epididymis were higher in the experimental groups than in the control. Sperm motility and progression were significantly reduced in the bisphenol A and methoxychlor + bisphenol A groups. Histological observation showed a reduced number of sperm, smaller seminiferous tubules, and destroyed lumen in the methoxychlor + bisphenol A group compared to the other groups. In conclusion, our study showed that methoxychlor and bisphenol A destroy male reproductive tissues and decrease sperm quality.

This study aims to investigate the effects of exogenous succinic acid (SCA) on Brucella (B.) abortus infection in macrophage RAW 264.7 cells and ICR mice. Firstly, the in vitro experiment was conducted by MTT cytotoxicity and bacterial internalization assay to evaluate the uptake of B. abortus into macrophage cells. Two non-cytotoxic concentrations of SCA demonstrated attenuated invasion of Brucella into macrophages at 30 and 45 min post- infection (pi). Secondly, ICR mice were treated with SCA and infected with B. abortus. On day-14 pi, spleen and blood serum were collected to evaluate the bacterial burden and total spleen weight as well as the production of cytokine/chemokine, respectively. The results showed that SCA treatment promoted bacterial growth and reduced the total spleen weight in mice. Furthermore, SCA treatment increased the level of IL-10 cytokine in the sera, while dampening the production of MCP-1 chemokine compared to the control. The results of bacterial load in spleen and spleen weight together with cytokine/chemokine production profile in the sera indicated that SCA induced the host anti-inflammatory response which is beneficial for the survival of Brucella. Therefore, these findings suggest that SCA contributed to host immunity against Brucella infection and the emerging potential topic-immunometabolism should be invested for further investigations.

The present study was carried out to investigate the acute oral toxicity of Chamaecyparis obtusa (C. obtusa) essential oil in ICR male and female mice. Acute oral treatment with C. obtusa essential oil did not reveal any sign of toxicity or mortality in treated mice. Mouse body weights were not affected after single oral administration of C. obtusa essential oil during the 14-day observation period. In the hematological and blood biochemical analysis, all parameters of the treated group with 2,000 mg/kg body weight of the essential oil were not significantly different those of the control group. Therefore, the lethal dose 50 of the essential oil was estimated to be greater than 2,000 mg/ kg body weight in mice, which indicated that the essential oil is non-toxic. In conclusion, this study suggests that C. obtusa essential oil orally safe ICR mice.

This study examined the acute toxicity of Vital-Shoot containing reduced glutathione in male and female ICR mice. Mice were intraperitoneally injected the drug at dose levels of 0, 250, 500, 1,000 and 2,000 mg/kg body weight (BW) for single-dose toxicity test. There were no statistical differences in BW changes between the control and all treated groups. Based on hematological and blood biochemical analyses, the drug did not affect all parameters. In addition, markers for liver and kidney functions did not meaningfully change in all treated groups. Since there were no adverse effects from the drug in a single-dose intraperitoneal toxicity test, it was concluded that the lethal dose 50 (LD50) of Vital-Shoot is estimated to be >2,000 mg/kg BW.

본 연구의 목적은 벼메뚜기(Oxya chinensis sinuosa) 분말 섭취가 유산소성 운동훈련(트레드밀 달리기)의 병행 유무에 의해 ICR 생쥐의 에 너지 대사를 증가시키는지를 알아보고자 하는 것이다. 이 목적을 달성하기 위하여, 28 마리의 ICR 생쥐를 보통식 대조군(CON), 보통식 대조군 으로서 운동훈련 병행군(COEX), 벼메뚜기 분말이 혼합된 사료 섭취군(GH), 그리고 벼메뚜기 분말이 혼합된 사료를 섭취함과 동시에 운동훈련 을 병행군(GHEX)으로 구분하였다. 벼메뚜기 분말 사료섭취 및 운동은 6주간 진행하였다. 체중증가율은 유의하지 않았다. 지방량은 GH와 GHEX에서 유의하게 감소하였다. 혈중 glutamic oxaloacetic transaminase와 glutamic pyruvic transaminase 수준은 처치 집단간 변화가 없었다. 제2형 당수송체 및 제4형 당수송체는 처치 집단간 유의한 차이가 없었다. GHEX의 fibronectin type III domain-containing protein 5 단백질 발현량이 가장 높았다. AMP-activated protein kinase 단백질 수준은 GHEX에서 유의하게 증가하였다. Glycogen synthase kinase 3 beta 단백질 발현량은 GHEX가 CON과 비교할 때 감소하였다. 이러한 결과들은 벼메뚜기 분말을 섭취하면서 지구성 운동훈련을 하는 경우에 에너지 대사에 영향을 준다는 것을 제시하고 있다.

식용곤충은 대체 식량자원으로 관심이 증가되고 있다. 본 연구의 목적은 누에나방 번데기 분말 섭취 유무에 따른 저항성운동 훈련(등장성 수축)이 ICR 마우스의 근육량 증가에 미치는 영향을 분석하였다. 이를 위하여 ICR 마우스 28마리를 대조군(CON), 저항성운동 훈련군(EX), 누에나방 번데기 분말 섭취군(SP), 누에나방 번데기분말 섭취 저항성운동 훈련군(SPEX)으로 그룹 당 각각 7마리씩 분류하였다. 체중증가율은 EX와 SPEX가 CON과 SP에 비해 유의하게 억제되었다. 혈중 총 단백질 농도는 SPEX가 다른 그룹에 비하여 가장 높았다. 알부민 농도 변화는 운동훈련 병행 시에만 증가하였다. 혈액 GOT와 GPT 수준은 유의차가 없었다. Akt와 Gsk-3β의 단백질 발현의 유의차는 없었다. 그러나 번데 기 분말 섭취 시 Akt 증가 및 Gsk-3β의 감소 경향이 나타났다. 비복근 근육 양은 저항성 운동 훈련을 하였을 때만 증가하였다. 그리고 또한, 번데 기 분말 섭취 시 근육량은 유의차가 없었으나 증가하는 경향을 보였다. 이러한 결과는 저항성 운동훈련과 누에나방 번데기 분말 섭취는 간독성을 유발하지 않고 근육량을 증가시킬 수 있다는 점을 시사한다. 그러나 보다 상세한 결과를 제시하기 위해 부가적인 연구가 필요할 것이다.

To investigate the in vivo cognitive effects of syringic acid(SA), Y-maze and passive avoidance tests were performed in amyloid-β(Aβ)-induced cytotoxicity. Learning and memory impairment by Aβ neurotoxicity was partially recovered in Institute of Cancer Research(ICR) mice orally administered SA(10mg/kg of body weight). The SA treated group showed an inhibitory effect on acetylcholinesterase(AChE) that was extracted from mice brain tissue after in vivo tests. Aβ-induced oxidative stress was also examined by malondialdehyde(MDA) and 2',7,-dichlorofluorescein diacetate(DCF-DA) assays, and lipid peroxidation of brain homogenates and cellular oxidative stress were reduced by SA. In cell viability assays using 3-[4,5-dimethythiazol-2-yl]-2,5-diphenyl tetrazolium bromide(MTT), lactate dehydrogenase(LDH) leakage, and caspase 3/7 activity, the SA treated group showed relatively effective protection against Aβ-induced neurotoxicity compared to the others. Consequently, these results suggest that SA in black soybean seed coat extract might improve cognitive function because of its neuronal cell protective effects against oxidative stress and the inhibitory effect of AChE as a cholinergic enzyme.

This study was conducted to evaluate the accumulation and distribution of hydrophobically modified glycol chitosan (HGC) as a degradable nanoparticle in the body. To determine the movement of degradable HGC nanoparticles in the body, 20 mg/kg of lutetium177-labeled HGC (Lu177-HGC) with the size ranging from 320 to 400 nm was injected intravenously into ICR mice, and the amount of radioactivity remaining in blood and several organs was measured at various time points during the period of 5 days. In the pharmacokinetics analysis using the Lu177 radioisotope, the free Lu177 was mainly distributed and accumulated in the order of kidney>liver>lung at 1 day after the injection of the radioisotope. However, the Lu177-HGC showed a high distribution of nanoparticles in the order of liver>spleen>kidney during the experimental period of 5 days. These results would provide a basic pharmacokinetics for the use of HGC as a drug carrier in drug delivery system.

The objective of this study was to investigate the effects of soy hydrolysate fractions on appetite suppression and ghrelin releasing. In a short-term experiment, the cumulative food intake and serum ghrelin level were decreased significantly (p<0.05) during a 4-hr period after the interperitoneal injection of soy hydrolysate fractions (0.5, 1 g/㎏ BW), following a 12-hr period of food deprivation. In a long-term experiment, food efficiency ratio (FER) was also reduced significantly (p<0.05), when soy hydrolysate fractions (0.5, 1% in drinking water) were given orally for 8 wks. Therefore, we found that soy hydrolysate fractions affected food intake through appetite and ghrelin releasing in short-term and long-term experiments. In conclusion, this study indicated that soy hydrolysate fractions would diminish the sensation of hunger by reducing the secretion of orexigenic factors such as ghrelin that send satiety signals to the brain, terminating food intake.

This study was conducted in order to examine the safety of bee venom as an alternative for antibiotics using male ICR mice. Five-week-old male mice received a single intravenous injection of a dried honey bee venom at the concentration of 0.25 mg/kg (a clinical dose) or 0.5 mg/kg through the tail vein and various pathophysiological analyses were performed after three days. No significant differences in changes of body weight were observed between the saline-treated control group and the experimental groups. In the hematological analysis, none of the parameters were affected by bee venom. In blood biochemistry analysis, none of the markers were affected by administration of bee venom. Similarly, there were no significant effects on markers for liver, kidney, and skeletal muscle functions in all treated- groups. On macroscopic examination, no remarkable lesions were detected in these organs. Because there were no adverse effects of the bee venom in a single intravenous toxicity test for three days, it was concluded that bee venom could be a candidate for a safe natural antibiotic for use in the animal production industry.

Selenium is an essential micronutrient which functions as an essential constituent of selenoproteins. The selenoproteins play an important role in the body’s defense from free radicals associated with chronic diseases such as cancer. The effect of selenium on colon carcinogenesis was investigated using an experimental animal model. Five-week old ICR mice were acclimated for one week, and fed on the Fe-overloaded diet (450 ppm) with different Se diets (0.02, 0.1 or 0.5 ppm) for 12 weeks. Animals were injected intraperitoneally with azoxymethane (AOM, 10 mg/㎏ B.W. weekly for 3 weeks), followed by 2% dextran sodium sulfate (DSS) in the drinking water for a week. There were three experimental groups including low Se group (Lse), medium (normal standard diet for mice) Se (MSe), and high Se (HSe). The numbers of aberrant crypt foci (ACF) and aberrant crypt (AC) were measured in the colonic mucosa. The iron and selenium concentrations in liver was measured using ICP-AES. Glutathione peroxidase (GPx) activity was determined in the liver and colon. TUNEL assay for cell apoptosis and proliferating cell nuclear antigen (PCNA) staining for cell proliferation were performed. Immunohistochemical staining of β-catenin was also performed in mucous tissue of colon. The dietary Se decreased the numbers of ACF/㎠ and AC/㎠ in a dose-dependent manner. HSe diet significantly decreased the numbers of AC/㎠, compared with LSe diet (p<0.05). The tumor incidence rate in low Se diet group was 5% higher than medium Se diet group and 20% higher than high Se diet group. The activities of GPx in the liver and colon were dependent on the content of dietary selenium. Apoptosis-positive cells were also increased by dietary Se in a dose-dependent manner. PCNA-positive staining was weak in high Se group. β-catenin stained area was increased in low Se group while it was decreased in high Se group. These findings indicate that dietary selenium exert a protecting effect on colon cancer by inhibiting the development of ACF/AC, increasing GPX and apoptosis, and decreasing cell proliferation and expression of β-catenin in mice.

For application of nano-sized material in various fields, toxicity evaluation of nano-sized material is important. In the current study, a suspension of 50 nm-sized zinc oxide (ZnO) nanoparticles at a dose of 1 g/kg body weight was injected intraperitonially into mice in order to identify the toxicity of ZnO nanoparticles. After 24 h, the blood and liver were taken and analyzed. According to the results of hematological analysis, white blood cell (p<0.001), mean corpuscular hemoglobin (p<0.001), and mean corpuscular hemoglobin concentration (p<0.05) in the ZnO nanoparticle treated group showed a significant decrease, compared to the control group. In serum biochemistry analysis, alanine aminotransferase (p<0.001) and aspartate amino-transferase (p<0.05) also induced a significant increase in the ZnO nanoparticle treated group, compared with the control group. In the histopathological examination, liver in mice treated with ZnO nanoparticles showed edema and degeneration in hepatocytes. Therefore, it is concluded that the liver is the target organ for 50 nm ZnO intraperitoneal exposure. In the future, greater attention should be paid to the potential toxicity induced by various routes and doses of ZnO nanoparticles.

본 연구에서는 azoxymethane (AOM)과 dextran sodium sulfate (DSS)로 유도된 대장 발암과정에 대한 셀레늄의 방어 효과를 조사하였다. 셀레늄 결핍(0.02 ppm Se), 정상(0.1 ppm Se), 과다(0.5 ppm Se)사료를 12주간 식이로 급여하여 혈액검사와 대장암 발생의 초기단계인 aberrant crypt foci (ACF)수를 측정했으며, 암 발생율을 조사하였다. ICP-AES 를 사용하여 간의 셀레늄 농도를 측정하였으며, 또한 셀레늄포함 항산화효소인 glutathione peroxidase (GPx) 활성을 알아보았다. 또한 TUNEL assay와 PCNA, β-catenin에 대한 면역조직 염색을 수행하였다. ACF 수 및 종양 발생률에 있어서, 셀레늄과다사료를 급여한 군이 정상셀레늄사료를 급여한 군보다 낮았으며, 셀레늄결핍사료를 급여한 군은 오히려 ACF 수 및 종양 발생률이 높았다. GPx 활성은 셀레늄의 섭취가 과다한 군에서 높게 나타났으며, 이 때, TUNEL 에서 apoptotic positive cell이 증가하는 것을 확인했다. 또 한 셀레늄의 섭취가 과다한 군에서 PCNA와 β-catenin의 발현이 감소됨을 볼 수 있었다. 본 마우스 모델실험에서 셀레늄은 여러 기전에 의해 대장암 발생을 억제할 수 있을 것으로 사료된다.

We examined the effect of Bulnesia sarmienti (BS) water extract on hyperlipidemia induced by a high-fat diet. ICR mice were fed a high-fat diet ad libitum for four weeks. Simultaneously, BS water extract was administered intragastrically at 0 mg/kg (control), 30 mg/kg, or 300 mg/kg once daily for four weeks. Male ICR mice were divided into four groups; normal control group (NC), high-fat diet+vehicle treatment group (HF), high-fat diet+BS of 30 mg/kg treatment group (HF+BS30), and high-fat diet+BS of 300 mg/kg treatment group (HF+BS300). The levels of serum biochemical parameters and histological appearances were evaluated. After four weeks, body weight gain and serum levels of triglycerides, total cholesterol, and Low-density lipoprotein (LDL)-cholesterol were significantly higher in the HF group than in the normal control group. Together, serum High-density lipoprotein (HDL)-cholesterol level in the HF group was lower than that in the normal control group. However, treatment with BS resulted in significantly reduced body weight gain and levels of serum triglycerides, total cholesterol, and LDL-choleterol. In addition, serum HDL-cholesterol level in the BS treatment group was significantly elevated, compared to that of the HF group. Histopathological evaluation of the liver showed fat accumulation and swelling of hepatocytes in the high-fat diet group; these abnormalities were ameliorated by treatment with BS. These results suggest that treatment with BS water extract resulted in dose-dependent prevention and mitigation of high-fat diet-induced hyperlipidemia.

Phytic acid (PA) is a naturallu 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. We investigated the preventive effect of PA on the formation of colonic aberrant crypt foci (ACF), a preneoplastic lesion, induced by azoxymethane (AOM). After acclimation for one week, six-week old male ICR mice were fed on the AIN-93G purified diet and PA (0.5% or 2% PA in water) for 8 weeks. The animals were treated with azoxymethane (AOM, 10 mg/kg b.w.) three times (0, 1, and 2 weeks) to induce colonic aberrant crypt foci (ACF). After sacrifice, the total numbers of aberrant crypts (AC) and ACF in colonic mucosa were counted after staining with methylene blue. Blood and serum were analyzed with a blood cell differential counter and an automatic serum analyzer. AOM treatment without PA induced the total numbers of 85.7 ± 12.9 and 115.2 ± 19.9, respectively. PA at the dose of 2% AC/colon by PA at the dose of 0.5% were 73.4 ± 12.9 and 115.2 ± 19.9, respectively. PA at the dose of 2% significantly decreased the ACF and AC numbers to 56.5 ± 14.6 and 95.4 ± 17.2, respectively (p＜0.01). PA at the doses of 0.5 and 2% decreased the numbers of ACF and AC/colon in a dose-dependent manner. Although some parameters in blood counts and serum chemistry were changed compared with the control, no specific toxicity was found. Theses findings suggest that phytic acid can be a chemopreventive agent for colon carcinogenesis resulting from inhibition of the development of ACF in ICR mice.

시험물질 산삼배양추출물의유전독성 평가를 위해 수컷 ICR 마우스 골수세포를 이용한 소핵시험을 실시하였다. 1회 투여 최고량은 예비 시험에서 결정하였다. 약 7주령의 수컷 마우스에 시험물질 0, 500, 1,000 및 2,000 mg/kg의 용량을 1일 1회 2일간 복강내 투여하고, 최종 투여로부터 약 24시간 후에 골수세포를 수거하여 소핵 유발과 세포독성을 평가하였다. 개체당 2,000개의 다염성적혈구(michromatic crythrocyte, PCE)중에 나타나는 소핵을 가진 다염성 적혈구(micronucleated polychromatic erythrocyte, MNPCE)의 수를 게수한 결과, 모든 시험물질 투여군은 음성 대조군에 비해 통계학적으로 유의한 증가는 나타나지 않았으며 일반 증상에서도 모든 시험군은 투여로 인한 것으로 판단되는 증상은 관찰되지 않았다. 부검시 체중에 있어서는 시험물질 최고 용량군에서 유의한 감소가 관찰되었다. 따라서 산삼배양추출물은 위 시험 조건에서, 본 시험에 사용한 마우스 골수세포에 소핵을 유발하지 않는 것으로 사료된다.