• Title/Summary/Keyword: Dose toxicity study

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Comparative Evaluation of Probiotic Activities of Bifidobacterium longum MK-G7 with Commercial Bifidobacteria Strains

  • Jung, Hoo-Kil;Kim, Eung-Ryool;Ji, Geun-Eog;Park, Jong-Hyun;Cha, Seong-Kwan;Juhn, Suk-Lak
    • Journal of Microbiology and Biotechnology
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    • v.10 no.2
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    • pp.147-153
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    • 2000
  • This study was conducted to compare probiotic activities and physiological functions of Bifidobacterium longum Mk-G7 with weveral commercial and type strains of bifidobacteria. bif. longum MK-G7 showed the highest acid tolerance against HCl and acetic acid, whereas bif. infantis Y-1 showed the lowest acid tolerance and more than 4 log cycles of viable cell count decreased due to acid injuty. Viable cell counts of bifidobacteria strains decreased more than 1.5 log cycles owing to oxygen toxicity, with the exception of Bif. longum MK-G7, Bif. infantis Y-2, Bif. longum Y-3, Bif. longum Y-6, and Bif. longum RD-13 showed the highest bile tolerance, whereas Bif. longum MK-G7 showed a medium level of bile tolerance. Only Bif. longum MK-G7 howed much higher antibiotic resistance against both tetracycline and penicillin-G in the MIC(minimum inhibitory concentration) level of 24.8 mg/I and 0.52mg/I, respectively. Bif longum Y-6, and Bif. bifidum ATCC 29539 showed more than 80% of anti-mutagenicity against NQO(4-nitroquinolinel-oxide). Since the production of cytokines such as $TNF(tumor necrosis factor)-{\alpha}$ and IL (interleukin)-6, and NO(nitric oxide) in the macrophage cell line Raw 264.7 cells increased as Bif. longum MK-G7 cell concentration increased, ti was suggested that Bif. longum MK-G7 is able to enhance immunopotentiating activity in vitro. When freeze-dred Bif. longum MK-G7 was administered to mice at the dose of 1,2,4, and 6 g/kg of body weight, all of the mice survived in all feeding groups, proving the GRAS(generally recognized as safe) status of Bif. longum MK-G7. When fermented milk containing Bif. longum MK-G7 was administered to human volunteers, viable cell count of total bifidobacteria and anaerobes in the feces increased up to 0.5 log cycles more than before the administration. In particular, Bif. logum MK-G7 ingibited the growth of Bacteroides at the level of 1.0-1.5 log cycles.

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Protective Effects of Pyrus pyrifolia NAKAI Leaf Extracts on UVB-induced Toxicity in Human Dermal Fibroblasts (자외선B 노출로 인해 손상된 피부세포에 대한 돌배나무잎 추출물의 보호효과)

  • Koh, Ara;Choi, Songie;Kim, Yong-ung;Park, Gunhyuk
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.42 no.1
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    • pp.87-94
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    • 2016
  • Skin damage is mainly caused by environmental factors such as ultraviolet light, heat, and smoking. It is known that reactive oxygen species production is commonly involved in the pathogenesis of skin damage induced by these factors, causing skin aging. Pyrus pyrifolia Nakai continues to be a popular and highly consumed fruit in many countries with known beneficial effects including antitumor, antioxidative, and anti-inflammatory effects. However, there is no evidence of a therapeutic effect of Pyrus pyrifolia extract (PPE) against skin aging via inhibition of mitochondria-mediated apoptosis. In this study, we investigated PPE protective effect against photoaging induced by UVB ($50mJ/cm^2$) in HS68 human dermal fibroblasts. Lactate dehydrogenase assay showed that PPE significantly protected HS68 cells against UVB-induced damage in a dose-dependent manner. Other assays using DCF-DA demonstrated that PPE protected HS68 cells by regulating reactive oxygen species production. PPE also regulated mitochondrial dysfunction and mitochondrial membrane potential induced by UVB, and inhibited UVB-induced caspase-3 activity. These results indicate that PPE protects human dermal fibroblasts from UVB-induced damage by regulating the oxidative defense system.

Anti-aging and Anti-melanogenesis Effect of Cimicifuge dahurica, Coptis chinensis, Phellodendri amurense and Magnol obovata Extracts Mixture (승마, 황련, 황백, 후박 추출 혼합물의 항노화 및 멜라닌 생성 저해효과)

  • Shin, Seo Yeon;Kim, Gue Won;Kang, Se Won;Cho, Hong Suk;Kim, Eun Ji;Park, Kyung Mok
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.43 no.1
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    • pp.1-10
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    • 2017
  • Cimicifuge dahurica (C. dahurica), Coptis chinensis (C. chinensis) and Phellodendri amurense (P. amurense) extracts has an detoxification effect and Magnol obovata bark (M. obovata) extracts has an antibacterial effect in oriental medicine. This study investigated the possibility of the extract mixture as a functional cosmetic ingredient by mixing C. dahurica, C. chinensis, P. amurense and M. obovata extracts. MTT assay was carried out for toxicity test and DPPH/ABTS experiments for antioxidant effects of the extract mixture. Results show that the extract mixture was safer and antioxidant effects in a dose-dependent manner than single extract of the mixture. The mixture effectively inhibited NO (nitric oxide) production, which indicate good efficacy for anti-inflammation. The mixture also protected UVB-induced cell damage and increased type 1 pro-collagen synthesis in fibroblast. In addition, it's treatment inhibited the melanin synthesis and tyrosinase activity by lowering expression of MITF, tyrosinase and TRPs in B16F10 melanoma cell. These results suggest that medicinal herbal extract mixture may be useful as a functional ingredient for anti-aging and skin whitening cosmetic formula.

Establishment of the Korean Tolerable Daily Intake of Bisphenol A Based on Risk Assessments by an Expert Committee

  • Choi, Chan-Woong;Jeong, Ji-Yoon;Hwang, Myung-Sil;Jung, Ki-Kyung;Lee, Kwang-Ho;Lee, Hyo-Min
    • Toxicological Research
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    • v.26 no.4
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    • pp.285-291
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    • 2010
  • Recently, reproductive and neurobehavioral effects of bisphenol A (BPA) have been documented, and thus a review was requested for BPA management direction by the government. Therefore, this study was performed to establish a Korean tolerable daily intake (TDI) for BPA. An expert committee, consisting of specialists in fields such as toxicology, medicine, pharmacology, and statistics, was asked to evaluate BPA health based guidance values (HbGVs). Although many toxicological studies were reviewed to select a point of departure (POD) for TDI, rat and mouse reproductive studies by Tyl et al. (2002, 2006), which were performed according to GLP standards and OECD guidelines, were selected. This POD was the lowest value determined from the most sensitive toxicological test. The POD, a NOAEL of 5 mg/kg bw/day, was selected based on its systemic toxicity as critical effects. An uncertainty factor of 100 including interspecies and intraspecies differences was applied to calculate the TDI. According to the evaluation results, a TDI of BPA for Korean was suggested at 0.05 mg/kg bw/day. In addition, the BPA exposure level based on food consumption by the Korean population was estimated as 1.509 ${\mu}g/kg$ bw/day, and the HI was evaluated at 0.03 when the TDI of 0.05 mg/kg bw/day was applied. This HI value of 0.03 indicated that hazardous effects would not be expected from BPA oral exposures. Although highly uncertain, further studies on low dose neurobehavioral effects of BPA should be performed. In addition, it is recommended that the 'as low as reasonably achievable' (ALARA) principle be applied for BPA exposure from food packaging materials in newborn infants and children.

Gene Expression Profiling of Acetaminophen Induced Hepatotoxicity in Mice

  • Suh, Soo-Kyung;Jung, Ki-Kyung;Jeong, Youn-Kyoung;Kim, Hyun-Ju;Lee, Woo-Sun;Koo, Ye-Mo;Kim, Tae-Gyun;Kang, Jin-Seok;Kim, Joo-Hwan;Lee, Eun-Mi;Park, Sue-Nie;Kim, Seung-Hee;Jung, Hai-Kwan
    • Molecular & Cellular Toxicology
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    • v.2 no.4
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    • pp.236-243
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    • 2006
  • Microarray analysis of gene expression has become a powerful approach for exploring the biological effects of drugs, particularly at the stage of toxicology and safety assessment. Acetaminophen (APAP) has been known to induce necrosis in liver, but the molecular mechanism involved has not been fully understood. In this study, we investigated gene expression changes of APAP using microarray technology. APAP was orally administered with a single dose of 50 mg/kg or 500 mg/kg into ICR mice and the animals were sacrificed at 6, 24 and 72 h of APAP administration. Serum biochemical markers for liver toxicity were measured to estimate the maximal toxic time and hepatic gene expression was assessed using high-density oligonucleotide microarrays capable of determining the expression profile of >30,000 well-substantiated mouse genes. Significant alterations in gene expression were noted in the liver of APAP-administered mice. The most notable changes in APAP-administered mice were the expression of genes involved in apoptosis, cell cycle, and calcium signaling pathway, cystein metabolism, glutatione metabolism, and MAPK pathway. The majority of the genes upregulated included insulin-like growth factor binding protein 1, heme oxygenase 1, metallothionein 1, S100 calcium binding protein, caspase 4, and P21. The upregulation of apoptosis and cell cycle-related genes were paralleled to response to APAP. Most of the affected gene expressions were returned to control levels after 72 hr. In conclusion, we identified potential hepatotoxicity makers, and these expressions profiling lead to a better understanding of the molecular basis of APAP-induced hapatotoxicity.

Effect of Saururus Chinensis in RANKL-induced Osteoclast Differentiation (삼백초 추출물이 뼈 파괴세포 분화에 미치는 효과)

  • Kim, Jung Young;Hyuk, Jungjong;Lee, Myeung Su;Lee, Chang Hoon;Kim, Yun Kyung;Jeon, Byung Hoon;Kwak, Han Bok;Kim, Ju-Young;Choi, Min-Kyu;Kim, Jeong Joong;Oh, Jaemin
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.26 no.6
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    • pp.869-873
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    • 2012
  • Balance between bone-forming osteoblasts and bone-resorbing osteoclasts is important in bone homeostasis. Unusual balance between bone-forming osteoblasts and bone-resorbing osteoclasts leads to bone diseases, such as osteoporosis. Saururus chinensis has been widely used in oriental medicine. Saururus chinensis has been known that has antioxidant and anticancer effect. But, the effect of Saururus chinensis in osteoclast differentation remains unknown. We examined the effect of Saururus chinensis in receptor activator of nuclear factor-${\kappa}B$ ligand (RANKL)-induced osteoclast differentiation. From the results of our study, we found that saururus chinensis clearly inhibited RANKL-induced osteoclast differentiation in bone marrow macrophages (BMM) in a dose dependent manner without toxicity. Saururus chinensis inhibited the phosphorylation of JNK, P38, AKT, and ERK induced by RANKL. The mRNA expression of NFATc1, TRAP, and OSCAR induced by RANKL was inhibited by Saururus chinensis treatment. Moreover Saururus chinensis suppressed the protein expression of c-Fos and NFATc1 in BMMs treated with RANKL. These results suggest that Saururus chinensis may be a useful drug in the treatment of bone-related disease.

Time Serial Concentration of Phthalate Esters and Bisphenol-A Contaminated from Spring Water Container's Cap and Seal Film

  • Park Chan Koo;Shin Jeong Sik;Kim Min Young;Kim Pan Gyi
    • Journal of Environmental Health Sciences
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    • v.31 no.6
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    • pp.457-466
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    • 2005
  • Industrial plasticizers such as phthalates can induce peroxisome proliferation. A growing concern among environmental and health groups has arisen because phthalates such as di-2-ethy1hexy1 phthalate (DEHP) and DBP may cause hormonal disorders, reproductive toxicity, hepatocellular tumors, genital disorders owing to a capacity to bind estrogen receptors, and a low-dose toxic action during certain periods of fetal development. Phthalate esters are used extensively as a plasticizer for plastic manufacture such as PVC bags and medical devices. This study investigated the effects of leached components from spring water container's cap and seal film. Phthalates, e.g. dimethy1 phthalate (DMP), diethy1 phthalate (DEP), di-n-buty1 phthalate (DBP), benzy1buty1 phthalate (BBP), di-(2-ethy1hexy1) phthalate (DEHP), and bisphenol A (BPA) were measured in the spring water. The bisphenol A was not detected or below the detection limit on the leaching from cap, sealing or spring water. DEHP were detected 90-116 ppb on the leaching from seal after 2 weeks, and 0.48-0.51 ppb from the spring water after I week. BBP were measured from seal within 1 week 25.4-66 ppb and below 0.12 ppb from spring water within 2 days. DMP were detected from seal within 2 weeks 51-68.5 ppb and 0.12 ppb after 2 weeks. DEP were measured from seal within 2 weeks 48.1-141 ppb and the concentrations were increased by the time from 0.10 to 0.31 ppb at spring water. DBP were detected from the seal within 2 weeks 92.3-5100 ppb and the concentration were decreased by the time from 0.24 to 0.10 ppb at spring water. These results indicate that some phthalate esters contaminated with spring water using the intact cap and seal film. It is concluded that the measured levels of phthalates leaching from these materials might in vivo only be slightly less than 1/10 of the LOAEL.

Effects of Combination of Nitrate with ${\beta}$1-4 Galacto-oligosaccharides and Yeast (Candida kefyr) on Methane Emission from Sheep

  • Sar, C.;Santoso, B.;Gamo, Y.;Kobayashi, T.;Shiozaki, S.;Kimura, K.;Mizukoshi, H.;Arai, I.;Takahashi, J.
    • Asian-Australasian Journal of Animal Sciences
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    • v.17 no.1
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    • pp.73-79
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    • 2004
  • The objective of the present study was to determine whether ${\beta}$1-4 galacto-oligosaccharides (GOS) and Candida kefyr combined with nitrate as manipulators could suppress rumen methanogenesis without nitrate poisoning in sheep. Four rumen fistulated wethers were allocated to a $4{\times}4$ Latin square design. Nitrate (1.3 g $NaNO_3$ $Kg^{-0.75}$body weight) with and without GOS and Candida kefyr were administered into the rumen through fistula as a single dose 30 min after the morning meal. GOS and Candida kefyr were supplemented by sprinkling onto the feed and through rumen fistula, respectively. The four treatments consisted of saline, nitrate, nitrate plus GOS and nitrate plus GOS plus Candida kefyr. Physiological saline was used as the control treatment. Compared to saline treatment, the administration of nitrate alone resulted in a very marked decrease in rumen methanogenesis and an increase in rumen and plasma nitrite production and blood methaemoglobin formation consequently causing a decline in oxygen consumption, carbon dioxide production and metabolic rate. When compared to nitrate alone, the simultaneous administration of nitrate with GOS decreased nitrite accumulation in rumen and plasma and nitrate-induced methaemoglobin, while retaining low methane production. However, GOS could not fully restore metabolic parameters reduced by nitrate. When compared to the simultaneous administration of nitrate with GOS, the simultaneous administration of nitrate with GOS plus Candida kefyr lowered rumen methanogenesis to a negligible level, but did not decrease rumen and plasma nitrite accumulation as well as blood methaemoglobin formation. Thus, these results suggest that combination of nitrate with GOS may be a potent manipulator to suppress rumen methanogenesis with abating the hazards of nitratenitrite toxicity in ruminants.

Radiation Therapy for Primary Eyelid Cancers in Tunisia

  • Belaid, A;Nasr, C;Benna, M;Cherif, A;Jmour, O;Bouguila, H;Benna, F
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.7
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    • pp.3643-3646
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    • 2016
  • Management of eyelid cancers is based on surgery and/or radiotherapy (RT). The treatment objective is to control tumors with acceptable functional and esthetic outcomes. The aim of this study was to evaluate the results of radiation therapy in management of epithelial eyelid cancers, reviewing retrospectively the clinical records of patients treated in our institution from January 1989 to December 2013. We focused on clinical and histological features, treatment characteristics, tolerance and disease control. One hundred and eight patients (62 men and 46 women) were enrolled, with a mean age of 61 years [ranges 15-87]. The most frequent tumor location was the inner canthus (42.6%). Median tumor size was 21 mm [ranges 4-70]. Histological type was basal cell carcinoma in 88 cases (81.5%), squamous cell carcinoma in 16 (14.8%) and sebaceous carcinoma in 4 (3.7%). Radiation therapy was exclusive in 67 cases (62%) and post-operative for positive or close margins in the remaining cases. Kilovoltage external beam radiotherapy (KVRT) was used in 63 patients (58.3%) and low-dose-rate interstitial brachytherapy in 37 (34.3%). Eight (7.4%) were treated with cobalt or with a combination of KVRT-cobalt, KVRT-electron beams, KVRT-brachytherapy or cobalt-electron beams. The total delivered radiation doses were 70 Gy (2 Gy/fraction) in 62 patients (57.4%), 66 Gy (2 Gy/fraction) in 37 (34.3%) and 61.2 Gy (3.4Gy/fraction) in 9 (8.3%). After a median follow-up of 64 months, we noted 10 cases of local recurrences(9.2%): 7 after exclusive and 3 after post-operative RT. No local recurrence occurred in patients treated with brachytherapy. Actuarial 5-year local recurrence-free rate, disease-free survival and overall survival were respectively 90%, 90% and 97%. T-stage was found to be a significant factor for recurrence (p=0.047). All acute radiation-related reactions were scored grade I or II. Delayed effects were eye watering in 24 cases (22.2%), eye dryness in 19 (17.6%), unilateral cataract in 7 (6.4%) and ectropion in 4 (3.7%). Radiation therapy and especially brachytherapy is an efficient treatment of eyelid cancers, allowing eye conservation and functional preservation with good local control rates and acceptable toxicity.

Effects of Antarctic Ocean Krill (Euphausia superba) Supplementation on Hepatic Functional Enzyme Activities and Fluoride Levels in Rats (남극해 크릴의 섭취가 흰쥐의 간 기능 효소 활성 및 불소 함량에 미치는 영향)

  • Jin, Dong-Hyeok;Oh, Da-Young;Lee, Young-Geun;Kang, Dong-Soo;Kim, Han-Soo
    • Journal of the Korean Applied Science and Technology
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    • v.35 no.2
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    • pp.485-491
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    • 2018
  • The purpose of this study was to probe the influences of krill (Euphausia superba) meal supplementation on a dose effect relationship between fluoride levels of krill meal and serum hepatic functional enzyme activity such as alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) in rats fed experimental diets for 5 weeks. There were no significant differences in the activities of ALP, AST, ALT, and LDH in sera among krill meal diet groups (KM10, KM20, KM30). However, these groups were significantly (p<0.05) lower enzyme activities than control group (CG). The fluoride levels of sera and organ tissues (liver, brain, heart, lung, kidney) in krill meal diet groups (KM10, KM20, KM30) were significantly increased by adding krill meal in comparison with CG. The results indicate that a difficult to found toxicity to the liver from krill meal diet groups.