• Preventive Nutrition and Food Science
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• 제11권2호
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• pp.115-119
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• 2006

The object of this study was to examine whether the germanium fortified yeast administered to SD rat is accumulated in the liver and kidney. The administration doses were within 2,000 mg/kg which is the level of NOAEL (no observed adverse effect level) proved through the previous study of single/consecutive oral toxicity test. There were no significant clinical symptoms and mortality following the administration of organic germanium-fortified yeast (0, 500, 1,000, 2,000 mg/kg) during the whole test period, and also no difference in the consumed amount of feed and water for each group. No significant abnormalities of hematology and blood chemistry parameters were found in all groups of organic germanium-fortified yeast (0, 500, 1,000, 2,000 mg/kg). The amount of germanium accumulated in liver and kidney was 0 g/kg by ICP-AES method in the group of organic germanium-fortified yeast. In the positive control group of $GeO_2$ (150 mg/kg), the amount of accumulation was shown to 3135.0 and 4277.2 g/kg in each female and male kidney and 1044.3 and 2135.8 g/kg in each female and male liver, respectively. Organic germanium-fortified yeast, a biosynthetic product resulting from putting germanium into yeast, did not show any clinical symptoms, blood chemical significance, and residues in kidney and liver. It could be inferred that the non-toxic amount of organic germanium-fortified yeast was up to 2,000 mg/kg.

• Toxicological Research
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• 제35권1호
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• pp.13-24
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• 2019

Numerous ethnomedicinal uses have been attributed to different parts of Annona senegalensis (ASE), including its uses as food and food additives. The present study investigated toxicological and antioxidant effects of 28 days administration of ethanol extracts of ASE stem bark to Wistar strain albino rats. Acute toxicity test was done to determine lethal dose in Wistar rats while sub-acute toxicity test was conducted on rats divided into four groups (A - control, B - 50 mg/kg, C - 100 mg/kg, D - 150 mg/kg, respectively and treated for 28 days. Oxidative stress markers in liver and kidney as well as hepatic succinate dehydrogenase activity in the mitochondrial and post mitochondrial fractions (PMF) were evaluated. The $LD_{50}$ value of ASE was > 2,000 mg/kg. White blood cell counts gradually increased, but red blood cell counts and haematocrits level decreased significantly (p < 0.05) by about 50%. Liver enzymes in the serum and mitochondrial succinate dehydrogenase activity increased significantly (p < 0.05). Superoxide dismutase and catalase activities also increased in liver mitochondria and PMF while malondialdehyde (MDA) and reduced glutathione levels increased only in the PMF. Furthermore, only MDA levels increased significantly in the kidney after 28 days extract administration. Histopathological examination showed hepatic necrosis and no obvious signs of nephrotoxicity. Anona senegalensis is relatively safe, but prolonged ingestion could induce oxidative stress and impair ATP synthesis through the modulation of the activity of mitochondrial succinate dehydrogenase.

• 대한한의학방제학회지
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• 제31권4호
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• pp.327-339
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• 2023

Objectives : This study conducted a repeated dose 90-day oral toxicity test in order to up-cycling Schisandra fruit extract powder(SFEP) using discarded Schisandra chinensis by-products and evaluated the NOAEL of SFEP. Methods : SD-rats were orally administered SFEP at concentrations of 0, 62.5, 125, and 250 mg/kg once daily for 90 days. Body weights and clinical signs were observed during the administration period. After completion of the experiment, the experimental animals were autopsied to observe necropsy findings and organ weights changes, and hematological parameters and blood chemistry values were measured. Results : During the SFEP administration period, clinical signs such as salivation, wounds, and erosion were sporadically observed in 1 to 2 animals. In the SFEP 250 mg/kg administered group, weights of the liver and thyroid gland significantly increased compared to the control group, but no significant changes were observed in organ weights according to body weights. As a result of measuring hematological parameters and blood chemistry values, a decrease in RDW, T-BIL, and TBA, and an increase in TP, ALB, and Ca were observed due to SFEP administration. However, these changes following SFEP administration were accidental and not dose-dependent. Additionally, no correlation was found between gender and other parameters. Conclusions : Therefore, the NOAEL of SFEP was confirmed to be 250 mg/kg.

• 디지털융복합연구
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• 제11권4호
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• pp.339-350
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• 2013

홍삼 사포닌분획(SF)투여 시 TCDD(2,3,7,8-tetracholorodibenzo-${\rho}$-dioxin)투여(TT)에 의해 감소했던 웅성 기니피그의 체중과 간, 콩팥, 지라, 고환의 무게가 유의하게 증가하였다(p>0.01). SF투여 시 TCDD투여에 의해 감소했던 헤마토크릿 값, 적혈구 및 혈소판의 수, 아밀라아제 및 lactate dehydrogenase의 활성도, 요산, 총단백질 및 알부민의 양은 증가했고, 증가했던 백혈구의 수, 중성지질, 총콜레스테롤(TC), 혈당, 저밀도지단백질-콜레스테롤, 고밀도지단백질-콜레스테롤, 크레아티닌, 혈중 요소질소, 칼슘 및 인의 양과 creatinine kinase, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase의 활성은 감소하였다. 그리고 적혈구, 백혈구, 혈소판, 혈당, TC, 칼슘 및 알부민을 제외한 모든 지표들은 통계학적 유의성을 보였다(p>0.01). 이상의 결과로부터 SF는 TCDD에 의해 유도된 기니피그의 급성독성을 완화시켜 주는 효과가 있음을 알 수 있었다.

• 대한한의학방제학회지
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• 제13권2호
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• pp.1-16
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• 2005

Objectives: To find out the effects GGTl, an antiobestic drug widely used in clinics, has on the blood-antiobestic index and the toxicity index using the data from the hGHTg obese male rats. We looked closely into both of the two indices because GGTl antiobestic effect can happen not only by pharmacological action, but also by its toxicity. Also, we verified the difference in effect between GGTl and reductil (sibutramine), which has been approved by the FDA of the United States. Methods: After performing the experiments for 8 weeks on the hGHTg obese male rats divided into three groups: the control group, the GGTl group, and the reductil (RD) group, we anesthetized the rats with Diethyl ether and took a 3ml blood sample from the heart. Then, after coagulating the blood in room temperature by using the plasma separator, we centrifuged it for 25 minutes in 3,000rpm using the high-speed refrigerated centrifuge. We kept the separated plasma in a deep freezer at $-80^{\circ}C$, and repeatedly measured the antiobestic index and the toxicity index twice using the hematology biochemistry analyzer. Also, in order to judge the indirect toxicity index, we separated liver from kidney and observed them. Results: When we looked at the results of the analysis of covariance on the measuring elements related to the antiobestic index (TC, HDL, LDL, TG, and GLU), there was no significant difference among the groups in all measuring elements. Also, the results of the analysis of covariance on the two roups (RD group and GGTl group) showed that the p-values had no significant difference under the level of significance 0.05. When we looked at the result of the analysis of covariance on the measuring elements related to the toxicity index (GOT, GPT, GGT, CREA, UA, ALB, and TP), we could see that the p-values in GPT, ALB, and TP have a significant difference among the groups. Also, the results of the analysis of covariance about the measuring elements related to the toxicity index on both groups, RD group and GGTl group, showed no significant difference in the p-values of all of the measuring elements in the two groups, RD and GGTl group. Conclusions: In conclusion, through this experiment, the safety of GGTl has been approved, and although the verification on its medical effect has not been clearly approved, when we consider the fact that it belongs to the same group as reductil, an antiobestic drug approved by the FDA of the United States, we could indirectly verify that GGTl has an antiobestic effect. We believe that when doing a sample design for a future experiment, it needs to be performed on a greater sample size based on the power analysis that needs to be performed primarily in experiments, and a more accurate verification is needed through more systematic experiment plans.

• Archives of Pharmacal Research
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• 제27권10호
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• pp.1037-1042
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• 2004

Study of the effects of the methanolic extract of Tagetes patula roots on blood pressure led to the isolation of well known citric (1) and malic acid (7) as hypotensive, and pyridine hydrochloride (4) as hypertensive constituents of the plant along with a new constituent, 2-hydroxy, 5- hydroxymethyl furan (9). Citric acid and malic acid caused 71% and 43% fall in Mean Arterial Blood Pressure (MABP) of rats at the doses of 15 mg/kg and 30mg/kg respectively while pyridine hydrochloride produced 34% rise in the MABP of rats at the dose of 30mg/kg. $LD_{50}\;and\;LD_{100}$ of citric acid in mice have been determined as 545 mg/kg and 1000 mg/kg, respectively.

• 디지털융복합연구
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• 제11권1호
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• pp.299-308
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• 2013

TCDD 독성이 유발된 흰쥐 혈액의 생화학적 지표에 미치는 상엽 물추출물 (MLE)의 효과를 조사하였고 통계자료는 일원분산분석과 Scheffe의 사후검증을 하였다. TCDD 투여 시 감소했던 백혈구와 혈소판의 수가 MLE투여로 급격하게 회복(p<0.01)되어 면역기능 개선효과가 있었다. TT에 의해 감소했던 혈중 칼슘 및 마그네슘의 농도는 MLE 투여 시 유의하게 증가(p<0.01)하였으나 인의 농도는 TT군에 비하여 MLE군이 유의하게 감소(p<0.01)하였다. 신장 기능과 관련된 creatinine 및 blood urea nitrogen은 TT군과 MLE군 사이에 유의성은 없었으며, 요산은 TT군과 MLE군 모두에서 감소하였다. 한편 TT에 의해 증가했던 glucose 농도, amylase 및 lipase의 효소 활성도는 MLE 투여시 유의하게 감소(p<0.01)하여 혈당상승 억제효과가 있었다. Total protein, ${\gamma}$-GTP 활성은 TT와 MLE의 영향을 거의 받지 않았으나 TT에 의해 증가했던 AST, ALT 및 ALP의 활성도는 MLE 투여 시 모두 유의하게 감소(p<0.01)하여 간기능 개선의 효과가 있었다. 한편 Total cholesterol, triglyceride와 LDL-cholesterol의 경우 TT에 의해 유발된 고지혈 증상이 MLE 투여 시 유의하게 감소(p<0.01)하여 항고지혈 효과가 있었으며 HDL-cholesterol은 TT군과 MLE군 모두에서 증가하였다. 이와 같이 MLE는 TCDD독성이 유발된 흰쥐에서 독성을 완화시켜 주는 작용이 있음을 알 수 있었다.

• Journal of Nutrition and Health
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• 제38권1호
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• pp.48-55
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• 2005

Chitosan, which is a biopolymer, composed of glucosamine units linked by $\beta$-1, 4 glycoside bonds, is rich in shells of crustacean such as crabs and shrimps. Consumption of chitosan has been rapidly increased as a functional food. We examined effects of chitosan on the damages caused by lead (Pb) exposure in rats. Male Sprague-Dawley rats were divided into 8 groups (n = 64), then fed diets containing 3% cellulose (control) or 3% chitosan, each with 4 different lead doses (0 mg/d, 20 mg/d, 50 mg/d, and 100 mg/d) for 4 wks. Lead doses were given 3 times per week by oral administration. Blood lead levels in rats increased depending on the administered doses of lead. Rats fed chitosan diets showed lower blood lead concentration than did their respective controls. Effect of chitosan on the blood lead was more beneficial in rats exposed to lower lead (20 mg/d) than in rats exposed to higher lead (50 mg/d and 100 mg/d). Histological changes in erythrocytes and liver were also examined. Chitosan tended to reduce numbers of basophilic stippling erythrocytes and improve the histological liver changes in rats given various lead doses. The preventive effects of chitosan on liver damages were stronger in rats with higher lead than those with lower lead. These results indicate that chitosan has beneficial effects on both blood toxicological responses and histological damages of erythrocytes and liver induced by the administration of various lead doses.

• Toxicological Research
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• 제29권2호
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• pp.121-127
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• 2013

Nanotoxicological research has shown toxicity of nanomaterials to be inversely related to particle size. However, the contribution of agglomeration to the toxicity of nanomaterials has not been sufficiently studied, although it is known that agglomeration is associated with increased nanomaterial size. In this study, we prepared aerosols of nano-sized carbon black by 2 different ways to verify the effects of agglomeration on the toxicity and deposition of nano-sized carbon black. The 2 methods of preparation included the carbon black dispersion method that facilitated clustering without sonication and the carbon black dispersion method involving sonication to achieve scattering and deagglomeration. Male Sprague-Dawley rats were exposed to carbon black aerosols 6 hr a day for 3 days or for 2 weeks. The median mass aerodynamic diameter of carbon black aerosols averaged $2.08{\mu}m$ (for aerosol prepared without sonication; group N) and $1.79{\mu}m$ (for aerosol prepared without sonication; group S). The average concentration of carbon black during the exposure period for group N and group S was $13.08{\pm}3.18mg/m^3$ and $13.67{\pm}3.54mg/m^3$, respectively, in the 3-day experiment. The average concentration during the 2-week experiment was $9.83{\pm}3.42mg/m^3$ and $9.08{\pm}4.49mg/m^3$ for group N and group S, respectively. The amount of carbon black deposition in the lungs was significantly higher in group S than in group N in both 3-day and 2-week experiments. The number of total cells, macrophages and polymorphonuclear leukocytes in the bronchoalveolar lavage (BAL) fluid, and the number of total white blood cells and neutrophils in the blood in the 2-week experiment were significantly higher in group S than in normal control. However, differences were not found in the inflammatory cytokine levels (IL-$1{\beta}$, TNF-${\alpha}$, IL-6, etc.) and protein indicators of cell damage (albumin and lactate dehydrogenase) in the BAL fluid of both group N and group S as compared to the normal control. In conclusion, carbon black aerosol generated by sonication possesses smaller nanoparticles that are deposited to a greater extent in the lungs than is aerosol formulated without sonication. Additionally, rats were narrowly more affected when exposed to carbon black aerosol generated by sonication as compared to that produced without sonication.

• 대한약침학회지
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• 제7권1호
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• pp.37-51
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• 2004

Objective : Recently scolopendrid aqua-acupuncture has been a good effect on pain control but it has not been known about clinical safety. The purpose of this study was to investigate acute toxicity of scolopendrid aqua-acupuncture. Method : In order to prove the clinical safety of scolopendrid aqua-acupuncture, We have observed a bacteriological examination and clinical pathology test after scolopendrid aqua-acupuncture treatment. Balb/c mice were injected intravenous with Scolopendrid aquaacupuncture treatment for $LD_{50}$ and acute toxicity test. We analyzed physical reaction(side effect)and clinical pathology test before and after Scolopendrid aqua-acupuncture treatment of mice and 20 patients suffering from pain, who admitted department of Acupunture and Moxibustion, College of Oriental Medicine, Won-Kwang University Kwangju hospital. Results : In the Blood agar plate and Nutrient agar plate, a bacteriological examination did not show a bacillus. In acute $LD_{50}$ toxicity test, there was no mortality thus unable to attain the value. Examining the toxic response in the acute toxicity test, there was no sign of toxication. In acute toxic test, running biochemical serum test couldn't yield any differences between the control and experiment groups. In the 20 patients treated with Scolopendrid aqua-acupuncture, hematologic test did not show remarkable change. In the 20 patients treated with Scolopendrid aqua-acupuncture, Liver function test(AST, ALT, ALP) showed a slight decrease on the contrary, and abnormal rate showed a decrease of 5.0% compared with previous study. Reanl function test(BUN, Cr) and abnormal rate showed a decrease of 5.0% compared with previous study. In the 20 patients treated with Scolopendrid aqua-acupuncture, Electrolyte were normal range before and after treatment. In the Urine analysis of 20 patients, Leukocyte, Protein, Glucose, Keton, Bilirubin, U-bilinogen were not detected before and after Scolopendrid aqua-acupuncture treatment, and the rest almost made no difference.