• Title/Summary/Keyword: Toxic Metabolite

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Screening the level of cyanogenic glucosides (dhurrin) in sorghum accessions using HPLC analysis

  • Choi, Sang Chul;Chung, Yong Suk;Lee, Yun Gyeong;Park, Yun Ji;Kim, Changsoo
    • Proceedings of the Korean Society of Crop Science Conference
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    • 2017.06a
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    • pp.104-104
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    • 2017
  • Sorghum (Sorghum bicolor (L.) Moench.) is one of the most important crops for human and animal nutrition. Nonetheless, sorghum has a cyanogenic glucoside compound which can be degraded into hydrogen cyanide, toxic to humans and animals even with tiny amount. In consequence, breeding materials with a low cyanide level has been a top priority in sorghum breeding programs. To fulfill our long-term goal, we are screening sorghum accessions with low cyanide level, which would be an important breeding material for food safety. We collected seeds of various sorghum accessions and analyzed relevant metabolites to find useful breeding materials of sorghum accessions containing low cyanide. Fourteen wild relatives were obtained from the University of Georgia in US, a reference accession BTx623, and three local varieties from National Agrobiodiversity Center of Rural Development Administration in Korea, and one wild species from the Wild Plant Resources Seed Bank of Korea University in Korea. Sorghum plants were grown in plastic greenhouse under natural conditions. After growing, leaf samples were harvested at different developmental stages: seedling phase, vegetative phase (right before flowering), and reproductive phase (ripening). Using collected samples, quantification analysis were performed by an HPLC system for three metabolites (dhurrin, 4-hydroxybenzaldehyde, and 4-hydroxyphenylacetic acid) in sorghum plants. Prior to metabolome analysis, specific experimental condition for HPLC system was set to be able to separate three metabolites simultaneously. Under this condition, these metabolites were quantified in each accession by HPLC system. We observed that the metabolite contents were changed differently by developmental stages and accessions. We clustered these results into five groups as patterns of their contents by developmental stages. Most of accessions showed that 4-hydroxybenzaldehyde content was very high at seedling stage and decreased rapidly at vegetative phase. Interestingly, the patterns of dhurrin content were very different among clusters. However, 4-hydroxyphenylacetic acid content was maintained at low levels by developmental stages in most accessions. The results would demonstrate how dhurrin and alternative degradation pathways are differentiated in each accession.

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Compositional Change of Hepatic Bile Acid by Multiple Administration of DWP305, a Combined Preparation Containing Ursodeoxycholic Acid and Silymarin, in Rats (흰쥐에서 Ursodeoxycholic Acid 및 Silymarin을 함유한 의약조서울(DWP305)의 연용투여에 의한 간내 담즙산 조성변화)

  • Cho, Jae-Youl;Yeon, Je-Deuk;Nam, Kweon-Ho;Kim, Jeum-Yong;Yoo, Eun-Sook;Yu, Young-Hyo;Park, Myung-Hwan
    • YAKHAK HOEJI
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    • v.40 no.3
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    • pp.311-319
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    • 1996
  • DWP305, a preparation containing combination of ursodeoxycholic acid(UDCA), silymarin and vitamins ($B_1\;and\;B_2$), is a drug currently being developed for hep atic disorders. In order to evaluate the changes in hepatic function by multiple oral administration(2 and 4 weeks) of DWP305 in rats, several biochemical parameters in blood, bile acid composition, and the accumulation of UDCA and lithocholic acid(LCA),a toxic metabolite formed by enterobacteria, were examined using HPLC. In blood biochemical findings, DWP305 did not affect the normal level and there was no difference in total bile acid composition for UDCA, cholic acid(CA), deoxycholic acid(DCA), chenodeoxycholic acid(CDCA) and LCA compared to the UDCA administered group, although total ratio of UDCA and CA was different from normal group. In case of ratio of taurine and glycine conjugated forms, DWP305(186mg/kg as a UDCA) administered group was also similar to normal group and UDCA administered group, while high dosing of DWP305 was not different in the ratio of UDCA administered group(930mg/kg) but normal group. And the ratio of LCA was in order of UDCA(930mg/kg), DWP305(930mg/kg as a UDCA), UDCA(186mg/kg) and DWP305(186mg/kg as a UDCA) administered group, which was less than 4%. The free form of UDCA as well as most of bile acids was not detected at all in rat liver, indicating that there's no accumulation. These results suggest that multiple dosing of DWP305 in rats may not affect hepatic biotransformation and metabolism of bile acids.

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Pharmacokinetics of Anticancer Agent SB-31 in Rats & Rabbits and the Cardiovascular Effect on the Isolated Perfused Rat Heart & Blood Coagulation (SB-31의 Glycyrrhizin을 지표로 한 Rat과 Rabbit에서의 약물동태 및 심혈관계에 대한 효과 연구)

  • Kang, Won Ku;Park, Yong Soon;Lee, Dong Heum;Kwon, Kwang Il
    • Korean Journal of Clinical Pharmacy
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    • v.8 no.2
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    • pp.122-132
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    • 1998
  • SB-31 which contains Pursatilla, Licoris and Ginseng extracts was recently proved as an anticancer agent. In a preclinical effort to be applied this drug to human, pharmacokinetics of SB-31 was carried out in rats and rabbits. Glycyrrhizin(GZ), a saponin of Licoris was used as a standard ingradient for the pharmacokinetics of SB-31. The rat's blood, bile and urine samples were serially collected in femoral vein, common bile duct and bladder, respectively, after bolus i.v. injection at a dose of 1 or 1/5 ampul/rat and rabbit's blood samples from the marginal ear vein at a dose of 1 or 3 amp./rabbit. GZ and glycyrrhetic acid(GA), a major metabolite of GZ in the physiological samples were analysed by HPLC with UV detection. The decline of GZ in plasma concentration was generally biexponential at each dose. GZ was almost completely recovered in bile within 18 hour. GA wasn't detected in the samples with UV detector. In the rat, Vss and Kel at a dose of 1 and 1/5 ampul of SB-31 were $98.06\pm6.07\;ml,\;0.33\pm0.05\;hr^{-1}\;and\;65.46\pm11.19\;ml,\;0.68\pm0.25\;hr^{-1}$, respectively. Those in rabbits at a dose of 3 and 1 ampul of SB-31 were $235.24\pm30.72\;ml,\;0.13\pm0.36\;hr^{-1}\;and\;341.32\pm28.58\;ml,\;0.27\pm0.04\;hr^{-1}$, respectively. 'WinNonlin' was utilized for the compartmental analysis. A two-compartment model was chosen as the most appropriate pbarmaco-kinetic model. The data were best described by using a weighting factor of $1/y^2$. To evaluate the effect of SB-31 on cardiovascular system, serially diluted SB-31 was directly injected into coronary artery in the isolated perfused rat heart and the effect of PSF, PSH, saponins of Pursatilla, and SB-31 on PT, APTT of healthy human plasma was examined. Except the positive inotropic effect of ten times diluted solution of SB-31, there was no significant effect on LVDP, (- dp/dt)/(+dp/dt), heart rate and coronary flow in comparision with that of vehicle. SB-31 had no effect on PT but slightly delayed APTT about $6.9{\sim}11.5\%$. There was no significant effect of PSF and PSH on PT & APTT. Conclusively, SB-31 did not show any notable toxic effects on cardiovascular system.

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Hygienic Study of Traditional Foodstuffs Subjected to the Mycotoxin (Mycotoxin을 중심으로 한 전통식품의 위생학적 연구)

  • 정덕화
    • Journal of the East Asian Society of Dietary Life
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    • v.6 no.1
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    • pp.105-114
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    • 1996
  • Certain Fungi Including Aspergillus flavus produce low molecular secondary metabolite that is toxic to human and animals, which have been termed mycotoxin. Given the proper humidity and temperature like summer in Korea, are capable of growing of those hazard fungi and elaborating mycotoxin on almost any organic substrate such as traditional foodstuffs and their raw materials including rice, barley, corn, meju, doenjang and gochujang etc. Until now, some people have examined to isolate various fungi such as Aspergillus sp., Penicillium sp. and Fusarium sp. from traditional foodstuffs and raw materials, and have screened various mycotoxin producing strains. Some mycotoxin contamination such as aflatoxin, ochratoxin, deoxynivalenol (DON) and zearalenone etc. also have been confirmed from similar above samples. But these data are different each other and inconsistent in experimental conditions and methods. Especially, almost experiments have been finished for one time. So more consistent experimental method and data are necessary to evaluate objectiely the safety of traditional foodstuffs subjected to the mycotoxin. For this purpose, we have to apply a new advanced technology to develop more simple and rapid methods for determination of mycotoxin and also have to concentrate our efforts on activation of research and accumulation of technology nth sustaining investment of financial support and enlargement of research installation. With those harmonious efforts, it should be possible to examine continuously nd systematically the mycotoxin contamination in our traditional foodstuffs and to assure the safety of them. Then we can maintain and develop the better traditional foodstuffs suited to internationalization.

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Effects of Polygoni multiflori radix Liquors on the Memory Impairment of Rat (하수오 침출술이 흰쥐의 기억력 손상에 미치는 영향)

  • Kong, Hyun-Joo;Shin, Seung-Ryeul;Hwang, Su-Jung;Lee, Kyung Eun;Jang, Jung-Hyeon;Yang, Kyung-Mi
    • Culinary science and hospitality research
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    • v.22 no.4
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    • pp.128-142
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    • 2016
  • This study was carried out to investigate the effect of memory impairment in rats fed alcohol liquid diets. The rats were randomly divided into 4 groups. While the control(C) group received a diet containing 12% of the daily calories with isocarbohydrate, the other groups received a diet containing 12% of the daily total calories with 36% Soju (A), 25% Cynanchi wilfordii radix liquors (WA), and 25% Polygoni multiflori radix liquors (RA) for 6 weeks. After 6 weeks, ADH activity in the brain tissue of the Group A was found to be significantly lower than Group C but significantly higher than both Groups WA and RA(p<0.05). ADLH activity was revealed to be the highest in the Group WA (p<0.05). The concentration of acetaldehyde, a highly toxic metabolite, was the highest in the Group A, but its concentration decreased significantly if fed a liquid diet containing WA. The concentration of acetylcholine, which has a high correlation with memory impairment, was significantly lower in Group A, although Group RA group was the highest compared to the other groups (p<0.05). AChE activity of the Group A was higher than Group C but lower in Groups WA and RA (p<0.05).

The analysis of ethylene glycol and metabolites in biological specimens (생체시료에서 에틸렌 글리콜과 그 대사체 분석에 관한 연구)

  • Park, Seh-Youn;Kim, Yu-Na;Kim, Nam-Yee
    • Analytical Science and Technology
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    • v.24 no.2
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    • pp.69-77
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    • 2011
  • Ethylene glycol (EG) is produced commercially in large amounts and is widely used as antifreeze or deicing solution for cars, boats, and aircraft. EG poisoning occurs in suicide attempts and infrequently, either intentionally through misuse or accidental as EG has a sweet taste. EG has in itself a low toxicity, but is in vivo broken down to higher toxic organic acids which are responsible for extensive cellular damage in various tissues caused principally by the metabolites glycolic acid and oxalic acid. The most conclusive analytical method of diagnosing EG poisoning is determination of EG concentration. However, victims are sometimes admitted at a late stage to hospitals or died during emergency treatment like a gastric lavage or found rotten dead, when blood EG concentrations are low or not detected. Therefore, in this study, the identification of EG was not only performed by gas chromatograpyc-mass spectrometry (GC-MS) following derivatization but also further toxicological analyses of metabolites, glycolic acid (GA) and oxalic acid (OA), were performed by ion chromatography in various biological specimens. A ranges of blood concentrations (3 cases) was $10\sim2,400\;{\mu}g/mL$ for EG, $224\sim1,164\;{\mu}g/mL$ for GA and ND $\sim40\;{\mu}g/mL$ for OA, respectively, In other biological specimens (liver, kidney, bile and pleural fluid), a range of concentrations (3 cases) was ND $\sim55,000\;{\mu}g/mL$ for EG, ND $\sim1,124\;{\mu}g/mL$ for GA and ND $\sim60\;{\mu}g/mL$ for OA, respectively. Liver and kidney tissues were recommended specimens including blood because OA, a final metabolite of EG, was identified large amounts in these despite no detectable EG caused by some therapy.

Toxicity Evaluation of 'Bt-Plus' on Parasitoid and Predatory Natural Enemies (기생성 및 포식성 천적에 대한 작물보호제 '비티플러스'의 독성 평가)

  • Seo, Sam-Yeol;Srikanth, Koigoora;Kwon, Gi-Myon;Jang, Sin-Ae;Kim, Yong-Gyun
    • Korean journal of applied entomology
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    • v.51 no.1
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    • pp.47-58
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    • 2012
  • Effect of a new crop protectant 'Bt-Plus' on natural enemies was analyzed in this study. Tested natural enemies included two parasitic species of $Aphidius$ $colemani$ and $Eretmocerus$ $eremicus$, and four predatory species of $Harmonia$ $axyridis$, $Orius$ $laevigatus$, $Amblyseius$ $swirskii$, and $Phytoseiulus$ $persimilis$. 'Bt-Plus' was formulated by combination of three entomopathogenic bacteria ($Xenorhabdus$ $nematophila$ (Xn), $Photorhabdus$ $temperata$ subsp. $temperata$ (Ptt), $Bacillus$ $thuringiensis$ (Bt)) and bacterial metabolite (BM). All three types of 'Bt-Plus' showed significantly higher toxicities against fourth instar $Plutella$ $xylostella$ larvae than Bt single treatment. Two types of bacterial mixtures ('Xn+Bt' and 'Ptt+Bt') showed little toxicity to all natural enemies in both contact and oral feeding assays. However, 'BM+Bt' showed significant toxicities especially to two predatory mites of $A.$ $swirskii$ and $P.$ $persimilis$. The acaricidal effects of different bacterial metabolites were evaluated against two spotted spider mite, $Tetranychus$ $urticae$. All six BM chemicals showed significant acaricidal effects. The BM mixture used to prepare 'Bt-Plus' showed a high acaricidal activity with a median lethal concentration at 218.7 ppm (95% confidence interval: 163.2 - 262.3). These toxic effects of bacterial metabolites were also proved by cytotoxicity test against Sf9 cells. Especially, benzylideneacetone, which was used as a main ingredient of 'BM+Bt', showed high cytotoxicity at its low micromolar concentration.

Effects of Aminotriazole on Lung Toxicity of Paraquat Intoxicated Mice (Paraquat중독에 의한 폐독성에 미치는 Aminotriazole의 영향)

  • Lee, Seung-Il;An, Gi-Wan;Chung, Choon-Hae
    • Tuberculosis and Respiratory Diseases
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    • v.41 no.3
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    • pp.222-230
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    • 1994
  • Background: Paraquat, a widely used herbicide, is extremely toxic, causing multiple organ failure in humans. Paraquat especially leads to irreversible progressive pulmonary fibrosis, which is related to oxygen free radicals. However, its biochemical mechanism is not clear. Natural mechanisms that prevent damage from oxygen free radicals include changes in glutathione level, G6PDH, superoxide dismutase(SOD), catalase, and glutathione peroxidase. The authors think catalase is closely related to paraquat toxicity in the lungs Method: The effects of 3-amino-1,2,4-triazole(aminotriazole), a catalase inhibitor, on mice administered with paraquat were investigated. We studied the effects of aminotriazole on the survival of mice administered with paraquat, by comparing life spans between the group to which paraquat had been administered and the group to which a combination of paraquat and aminotriazole had been administered. We measured glutathion level, glucose 6-phosphate dehydrogenase(G6PDH), superoxide dismutase(SOD), catalase, and glutathione peroxidase(GPx) in the lung tissue of 4 groups of mice: the control group, group A(aminotriazole injected), group B(paraquat administered), group C(paraquat and aminotriazole administered). Results: The mortality of mice administered with paraquat which were treated with aminotriazole was significantly increased compared with those of mice not treated with aminotriazole. Glutathione level in group B was decreased by 20%, a significant decrease compared with the control group. However, this level was not changed by the administration of aminotriazole(group C). The activity of G6PDH in all groups was not significantly changed compared with the control group. The activities of SOD, catalase, and glutathione peroxidase(GPx) in the lung tissue were significantly decreased by paraquat administration(group B); catalase showed the largest decrease. Catalase and GPX were significantly decreased by aminotriazole treatment in mice administered with paraquat but change in SOD activity was not significant(group C). Conclusion: Decrease in catalase activity by paraquat suggests that paraquat toxicity in the lungs is closely related to catalase activity. Paraquat toxicity in mice is enhanced by aminotriazole administration, and its result is related to the decrease of catalase activity rather than glutathione level in the lungs. Production of hydroxyl radicals, the most reactive oxygen metabolite, is accelerated due to increased hydrogen peroxide by catalase inhibition and the lung damage probably results from nonspecific tissue injury of hydroxyl radicals.

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