• Title/Summary/Keyword: Toxicity Reduction

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Preparation of 5-Fluorouracil-Loaded Poly(L-lactide-co-glycolide) Wafer and Evaluation of In Vitro Release Behavior

  • Lee, Jin-Soo;Chae, Gang-Soo;An, Tae-Kun;Gilson Khang;Cho, Sun-Hang;Lee, Hai-Bang
    • Macromolecular Research
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    • v.11 no.3
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    • pp.183-188
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    • 2003
  • The controlled delivery of anticancer agents using biodegradable polymeric implant has been developed to solve the problem of penetration of blood brain barrier and severe systemic toxicity. This study was performed to prepare 5-FU-loaded poly (L-lactide-co-glycolide) (PLGA) wafer fabricated microparticles prepared by two different method and to evaluate their release profile for the application of the treatment of brain tumor. 5-FU-loaded PLGA microparticles were characterized by scanning electron microscopy (SEM), powder X-ray diffraction (XRD), and differential scanning calorimetry (DSC). SEM observation of the 5-FU-loaded PLGA microparticles prepared by rotary solvent evaporation method showed that 5-FU was almost surrounded by PLGA and significant reduction of crystallinity of 5-FU was confirmed by XRD. In case of release profile of 5-FU from 5-FU-loaded PLGA wafer fabricated microparticles prepared by mechanical mixing, the release profile of 5-FU followed near first order release kinetics. In contrast to the above result, release profile of 5-FU from 5-FU-loaded PLGA wafer fabricated microparticles prepared by rotary solvent evaporation method followed near zero order release kinetics. These results indicate that preparation method of the 5-FU-loaded PLGA microparticles to fabricate into wafers was contributed to drug release profile.

Proapoptotic and antitumor effect of Hangbaek-Tang(HBT) in a tumor transplanted mouse model (마우스 모델에서 항백탕 투여에 의한 종양 증식의 억제 및 Apoptosis의 유도)

  • Yun, Young-Gab;Kim, Jun-Hee;Song, Eun-Jung;Hwang, Jin-Ki;Nam, Sang-Yun
    • Herbal Formula Science
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    • v.17 no.2
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    • pp.73-83
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    • 2009
  • Objective : In vitro proapoptotic effect of Hangbaek-Tang (HBT) has been documented by one of us. In the present study, we aimed to demonstrate in vivo effect of HBT on tumor growth. Methods : In vitro selective cytotoxicity of HBT was examined by enumeration of viable cell numbers using BC3A mouse leukemic cells and normal spleen cells. In vivo effect of HBT (25 and 50 mg/mouse) on tumor growth was assayed using BC3A cells innoculated subcutaneously in the flank. Annexin-V apoptosis assay and PI staining was performed to determine the effective serum factor in HBT-treated mice. Leukocyte recruitment into peritoneum were analyzed by microscopy with a stained cytosmear of peritoneal lavage fluid. Results : HBT exhibited in vitro selective cytotoxicity to leukemic cells and did not show any toxicity on immune organs. In vivo i.p. administration of HBT induced significant reduction in tumor growth but not complete regression. Sera obtained from HBT-treated mice strongly inhibited BC3A cell growth in vitro and were revealed to markedly enhance apoptosis and accompanying cell death, when compared to those from PBS-treated mice. Abundant extravasation of leukocytes, especially neutrophils, into peritoneum was observed in HBT-treated mice. Conclusions : HBT causes leukemic, BC3A cell death in vivo via apoptosis as well as in vitro, for which functional involvement of leukocytes is suggested.

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The Effects of Shihosogan-san on Alcohol-induced Muscle Atrophy in Rats (흰쥐의 만성 알콜성 근위축에 시호소간산(柴胡疎肝散)이 미치는 효과)

  • Kim, Bum Hoi
    • Herbal Formula Science
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    • v.24 no.4
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    • pp.311-321
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    • 2016
  • Chronic or acute alcohol abuse often leads to liver injury associated with alcoholic hepatitis, liver fibrosis, cirrhosis, and liver cancer. In addition to the liver, alcohol abuse also induces a variety of other tissue injuries including pancreatitis, cardiomyopathy, neurotoxicity and muscle loss. Chronic skeletal muscle myopathy, independent of peripheral neuropathy, is well recognised in alcoholic patients. Several mechanisms may be involved in the pathogenesis of alcoholic myopathy. Ethanol is a potent inhibitor of muscle protein synthesis. Gastrocnemius and plantaris muscles are Type II fiber-predominant and usually considered representative of the musculature as a whole. Whereas, soleus muscle is Type I fiber predominant. Shihosogan-san is a traditional Korean medicine that is widely employed to treat indigestion and liver diseases. Muscle diseases are often related to liver diseases and conditions. We therefore tested the hypothesis that treatment with Shihosogan-san could ameliorate the ethanol-induced changes in muscle protein synthesis. Young male Sprague-Dawley rats were orally given 25% ethanol (5ml/kg, body weight) daily with Ethanol for 28 days. Normal group was similarly administrated with saline. In Shihosogan-san treated group, rats were orally administrated Shihosogan-san extract, and rats of EtOH group were given with the vehicle only. After 4 week, the morphology of gastrocnemius and plantaris muscles were assessed by hematoxylin and eosin staining. For comparative purposes, liver function was also investigated. The muscles from rats of EtOH group displayed a significant reduction in average cross section area compared to Normal group. Shihosogan-san treated group had increased fiber compared to the EtOH group. Moreover, Shihosogan-san treated group compared with EtOH group showed significantly decreased pro-apoptotic BAX expression and increased anti-apoptotic Bcl-2 expression. In conclusion, Shihosogan-san extract showed ameliorating effects on chronic alcohol toxicity in skeletal muscle.

Inhibitory Effect of Salvia miltiorrhiza Extract on Growth of Some Cancer Cells (단삼(Salvia Miltiorrhiza) 추출물의 암세포 증식 억제 효과에 관한 연구)

  • 정국찬;이지영;김동청;서성옥;황우익
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.29 no.4
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    • pp.726-731
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    • 2000
  • This study was performed to evaluate the antitumor activities of water and ethanol (EtOH) extract of Salvia miltiorrhiza in vitro and in vivo. The proliferation of the human hepatoma (HepG2), rectum cancer (HRT-18) and colon cancer (HT-29) cells was inhibited by administration of extracts in a dose-dependent manner. Particularly, EtOH extract inhibited proliferation of the cells more effectively than water extract did. The morphology of cells induced by EtOH extract was characterized by reduction of cell size and deformatin. Oral administration of the EtOH extract (3 mg/head) to tumor-bearing mice inhibited the tumor (sarcoma-180) growth by 35% and prolonged their survival rate by 61%. The EtOH extract was shown to be nontoxic at 37.5% mg/head/day on the acute toxicity test. These studies suggest that the EtOH extract of Salvia miltiorrhiza may have antitumor activity in vitro and in vivo.

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Effects of Prunella vulgaris labiatae extract on specific and non-specific immune responses in tilapia (Oreochromis niloticus)

  • Park, Kwan-Ha;Choi, Sanghoon
    • Journal of Animal Science and Technology
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    • v.56 no.1
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    • pp.3.1-3.7
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    • 2014
  • We examined the effects of Prunella vulgaris Labiatae (P. vulgaris L.) on specific and non-specific immune responses of Nile tilapia, Oreochromis niloticus. The optimal concentration without toxicity of P. vulgaris was determined to $30-40{\mu}g/ml$ in vitro and $120{\mu}g$/100 g of fish in vivo. P. vulgaris significantly elicited an antibody titer compared to FCA or ${\beta}$-glucan. ${\beta}$-glucan plus P. vulgaris group synergistically enhanced antibody production. No significant difference in antibody production was observed between P. vulgaris and P. vulgaris plus ${\beta}$-glucan group. A respiratory burst activity of head kidney (HK) leucocytes of tilapia administered with 300 or $500{\mu}g$ P. vulgaris was significantly (p < 0.05) enhanced compared with the PBS-injected control group and FCA-treated group. Maximum increase in the NBT reduction value was observed in $500{\mu}g$ P. vulgaris group but no significant difference was found between 300 and $500{\mu}g$ P. vulgaris group. The level of serum lysozyme activity was significantly (p < 0.05) higher in the 300 and $500{\mu}g$ P. vulgaris than $100{\mu}g$ P. vulgaris and FCA group. The phagocytic activities of HK leucocytes from tilapia administered with 300 and $500{\mu}g$ P. vulgaris were significantly (p < 0.05) higher than $100{\mu}g$ P. vulgaris and the control group. P. vulgaris was revealed with a good immunoadjuvant evoking the specific and non-specific immune responses of tilapia.

Effects of red ginseng total saponin on Menadione-induced hepatotoxicity in the rat (Menadione에 의해 유발된 간독성에 미치는 홍삼사포닌의 영향)

  • Jang, Bong-jun;Bae, Chun-sik;Cho, Yong-seong;Cha, Yong-ho;Park, Chang-won;Cho, Tae-hyun;Chang, Kyung-jin
    • Korean Journal of Veterinary Research
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    • v.37 no.3
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    • pp.619-627
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    • 1997
  • It is known that 2-methyl-1,4-naphtoquinone(menadione, MD) induces hepatotoxicities both in vivo and in vitro. These toxic effects are believed to result from oxidative damages to hepatocytes by "active oxygen" species via one-electron reduction of the naphtoquinone. The ginsenoside(GS) is a complex mixture of individual ginsenosides which is known to produce a range of effects on the cardiovascular and central nervous systems. In particular, GS has an antioxidant effect. In this experiment we studied the effect of GS from red panax ginseng(red ginseng total saponin, RGTS) on free radical-induced liver injuries by MD. Administration of MD($150{\mu}M$) caused an increase in aspartate aminotransferase(AST) activities and lipid peroxidation, decrease in alkaline phosphatase(ALP) activities and total bilirubin levels in blood, caused depletion of GSH and changes of antioxidant enzyme(superoxide dismutase, catalase) activities are shown in liver tissue. Administration of RGTS restored the AST levels that increased by MD, but catalase showed no significant changes. RGTS also had an effect of restoring the GSH level and had some synergistic effects with SOD. These data suggest that RGTS may have some protective effects on liver injury which is related with the oxygen free radical.

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Tributyltin chloride (TBTCl) toxicity on the oxygen consumption rate and histological changes of gill in the equilateral venus, Gomphina veneriformis (Bivalvia: Veneridae) (대복, Gomphina veneriformis 아가미의 조직학적 변화와 산소소비율에 미치는 TBTCl의 독성)

  • Park , Jung-Jun;Lee, Jung-Sick
    • Journal of fish pathology
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    • v.21 no.1
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    • pp.67-79
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    • 2008
  • This study was conducted to find out biological response of bivalves exposed to tributyltin chloride(TBTCl). The results of the study confirmed that TBTCl induce the reduction of oxygen consumption rateand histopathological feature in the gill structure of equilateral venus, Gomphina veneriformis. The experi-mental groups consisted of a control and 3 TBTCl exposure groups (0.4, 0.6 and 0.8 yg TBTCl L') and theexperimental period was 36 weeks. For histological analysis, gill tissues were fixed in Bouin's fluid andthen stained H-E stain, AB-PAS (PH 2.5) reaction and Masson's trichrome stain after having serially sec-tioned the tissue by paraffin method at thickness of 4-6 (an. The oxygen consumption rate was not signifi-cantly different between the control and exposure groups at 4 weeks, but in all exposure groups at 28 weeks,it was significantly different to the control. Gill of G. veneriformis had demibranch that attached two sheetsof lamellae and a lamella was composed of numerous filaments, numbering 25 on average. The frontal fila-ment zone had three types of cilia; frontal, latero-frontal and lateral depending on locations while the lateralcilia were the longest and largest in number. The mucous cells observed in filaments were more abundant in(542c) in AB-PAS (PH 2.5) reaction. Gill exposed to TBTCl was extended hemolymph sinus and increased hemocytes at 4 weeks, and then it showed increases of mucous cells and partially disappearance of frontalcilia. In the group of 0.8 yg TBTCl L' at 12 weeks, hypertrophy of frontal and latero-frontal epithelia wasobserved. Also it observed m decrease of mucous cell containing weekly acid mucosubstance and appearedpartially destruction muscle fiber bundle, In the groups of 0.4 and 0.6 ug TBTCl L' at 36 weeks, it appearedpartially modification of epithelia and in 0.8 us TBTCl L' group, observed filaments that come out chiti-nous rod from disappearance of frontal and latero-frontal epithelia.

Pre-validation of the OECD Enhanced Test Guideline 407 Protocol on Screening and Testing for Endocrine Disrupters (Propylthiouracil을 이용한 OECD enhanced TG407의 내분비계 장애 물질검색을 위한 유효화 실험)

  • 강경선;김대용;제정환;김태원;김형섭;박지은;윤준원;김경배;이지해
    • Toxicological Research
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    • v.17 no.3
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    • pp.203-213
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    • 2001
  • We investigated the toxic effects of propylthiouracil (PTU) In Sprague-Dawley (SD) rats to develop and validate an enhanced Protocol for Test Guideline 407 as OECD Project. Twenty male and female SD rats,7 weeks old, were treated with PTU in corn oil at levels of 0, 0.1, 1 and 10 mg/kg/day for 4 weeks orally. Clinical observation, body weight changes, food uptake, water consumption, urinalysis, estrus cycle and sperm analysis, serum chemist교, autopsy findings and histopathological findings were evaluated in this study. No clinical signs and mortality were observed in the study. The body weights and food uptakes in the group treated with 10 mg/kg/day were reduced from 3 weeks after the initiation of the treatment. The levels of 3,5,3'-triiodothyronine (T3) and thyroxine (T4, 3,5,3',5'-tetraiodothyrosine) were also significantly decreased in the group treated with 10 mg/kg/day. Also, the relative and absolute organ weights of thymuses were decreased. Thyroid glands of rats in the group treated with PTU 10 mg/kg/day were bigger than those of rats in the control group. In the histopathological examination, diffuse hyperplasia and hypertrophy of thyroid follicular cells were observed in all treatment groups, leading to the reduction of lumen size and papillary enfolding of lining epithelium. The degree of lesion was increased in a dose-dependent manner. The results suggested that PTU would cause toxicity in thyroid gland and decrease the levels of T3 and T4 in SD rats. However there were no effects on the other organ including testis and uterus especially in spermatogenesis and estrus cycle. On the basis of the results, enhanced protocol for Test Guideline (TG) 407 may be sensitive and reliable to detect endocrine-active substances like PTU.

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Effect of Lead on Ultrastructure and Enzyme Activities in Mouse Liver and Kidney (납(Pb)이 생쥐 간과 신장의 미세구조 및 몇가지 효소 활성에 미치는 영향)

  • Lee, S.I.;Yoo, C.K.;Choe, R.S.
    • Applied Microscopy
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    • v.15 no.1
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    • pp.13-30
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    • 1985
  • This study was undertaken to investigate the effect of lead on organisms. Mice received 15mg or 30mg of lead acetate per kg body weight every day for 1, 2 or 3 weeks, and the livers and kidneys were removed 24h after repeated injections. The livers and kidneys were used as sources for measurement of enzyme activities and for observation of alterations in ultrastructure. It was observed that body weights of mice treated with lead acetate were decreased when compared with those before treatment. This decrease in body weight was proportional to dose. The enzyme activities of succinate and malate dehydrogenases of experimental group that was treated with lead acetate for 1 week were nearly unchanged when compared with controls, but the enzyme activities of experimental group that was treated with lead acetate for 2 or 3 weeks were lower than those of controls. Changes in the enzyme activities were dependent on, but were not proportional to dose. Histologic examination of livers and kidneys after lead treatment showed that lead compound was accumulated and damaged in nucleus and mitochondria mainly. It was also observed that intranuclear inclusion bodies were formed only in epithelial cell of kidney proximal tubule after lead treatment. The overall changes in the ultrastructure were much greater in the livers than in the kidneys. From the above results, it nay be possible to conclude that the lead results in the decrease in body weight, reduction in the succinate dehydrogenate and malate dehydrogenase activities, and damages in the ultrastructure of kidney and liver in mouse. The presence of intranuclear inclusion bodies only in the kidney implies that these bodies protect the kidney from lead toxicity to some extent.

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Numerical Study on the Injector Shape and Location of Urea-SCR System of Heavy-duty Diesel Engine for Preventing $NH_3$ Slip (대형 디젤엔진용 SCR 시스템의 암모니아 슬립 억제를 위한 인젝터의 형상 및 위치에 관한 수치적 연구)

  • Jeong Soo-Jin;Lee Sang Jin;Kim Woo-Seung;Lee Chun Beom
    • Transactions of the Korean Society of Automotive Engineers
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    • v.14 no.1
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    • pp.68-78
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    • 2006
  • In the past few years, considerable efforts have been directed towards the further development of Urea-SCR(selective catalytic reduction) technique for diesel-driven vehicle. Although urea possesses considerable advantages over Ammonia$(NH_3)$ in terms of toxicity and handling, its necessary decomposition into Ammonia and carbon dioxide complicates the DeNOx process. Moreover, a mobile SCR system has only a short distance between engine exhaust and the catalyst entrance. Hence, this leads to not enough residence times of urea, and therefore evaporation and thermolysis cannot be completed at the catalyst entrance. This may cause high secondary emissions of Ammonia and isocyanic acid from the reducing agent and also leads to the fact that a considerable section of the catalyst may be misused for the purely thermal steps of water evaporation and thermolysis of urea. Hence the key factor to implementation of SCR technology on automobile is fast thermolysis, good mixing of Ammonia and gas, and reducing Ammonia slip. In this context, this study performs three-dimensional numerical simulation of urea injection of heavy-duty diesel engine under various injection pressure, injector locations and number of injector hole. This study employs Eulerian-Lagrangian approach to consider break-up, evaporation and heat and mass-transfer between droplet and exhaust gas with considering thermolysis and the turbulence dispersion effect of droplet. The SCR-monolith brick has been treated as porous medium. The effect of location and number of hole of urea injector on the uniformity of Ammonia concentration distribution and the amount of water at the entrance of SCR-monolith has been examined in detail under various injection pressures. The present results show useful guidelines for the optimum design of urea injector for reducing Ammonia slip and improving DeNOx performance.