• Title/Summary/Keyword: metabolite M2

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Effect of Permanent Hypoinsulinemia on Appetite, Performance, Carcass Composition, Blood Metabolites and Leptin Concentrations in Lambs

  • Moslemipur, F.;Torbatinejad, N.M.;Khazali, H.;Hassani, S.;Ghoorchi, T.
    • Asian-Australasian Journal of Animal Sciences
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    • v.22 no.6
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    • pp.827-835
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    • 2009
  • Insulin has crucial roles in energy metabolism in all mammals but has been less studied in ruminants. An experiment was conducted to investigate the effects of hypoinsulinemia induction on appetite, performance, carcass composition and blood metabolite levels in sheep. Treatments were intravenous injection of four doses of streptozotocin; 0, 25, 50 and 75 mg/kg BW named C, L, M and H, respectively. Twenty male lambs were divided into four treatment groups. Animals in group H could not continue the experiment because of abnormalities. The duration of the experiment was eight consecutive weeks, and injection was performed at the end of week 3. Feed and water intakes were measured weekly and weight changes of animals were recorded and used for calculation of other growth parameters. Blood samples were collected weekly via venipuncture at fasting and 2.5 h post-prandial and analyzed for hormones and blood metabolites. Results showed a marked hypoinsulinemia in group M with significant decrease in fasted and postprandial insulin concentrations and also fasted leptin concentrations vs. the control group C (p<0.05). Group M showed significant increases in blood glucose, triglycerides, cholesterol, total protein, blood urea nitrogen and ketone body levels vs. group C (p<0.05). After injection, animals in group M showed diabetic hyperphagia and enhanced water intake as compared to group C (p<0.05) but, despite increased feed intake, they did not gain more weight than controls (p<0.05), and consequently, their feed conversion ratio was greater. Protein and fat contents of meat and liver were not significantly different among groups (p>0.05). In conclusion, the results suggested a regulatory role of insulin in energy metabolism of ruminants by exerting two opposing effects; central catabolic and peripheral anabolic.

Exploring the Potentiality of Novel Rhizospheric Bacterial Strains against the Rice Blast Fungus Magnaporthe oryzae

  • Amruta, Narayanappa;Kumar, M.K. Prasanna;Puneeth, M.E.;Sarika, Gowdiperu;Kandikattu, Hemanth Kumar;Vishwanath, K.;Narayanaswamy, Sonnappa
    • The Plant Pathology Journal
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    • v.34 no.2
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    • pp.126-138
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    • 2018
  • Rice blast caused by Magnaporthe oryzae is a major disease. In the present study, we aimed to identify and evaluate the novel bacterial isolates from rice rhizosphere for biocontrol of M. oryzae pathogen. Sixty bacterial strains from the rice plant's rhizosphere were tested for their biocontrol activity against M. oryzae under in vitro and in vivo. Among them, B. amyloliquefaciens had significant high activity against the pathogen. The least disease severity and highest germination were recorded in seeds treated with B. amyloliquefaciens UASBR9 (0.96 and 98.00%) compared to untreated control (3.43 and 95.00%, respectively) under in vivo condition. These isolates had high activity of enzymes in relation to growth promoting activity upon challenge inoculation of the pathogen. The potential strains were identified based on 16S rRNA gene sequencing and dominance of these particular genes were associated in Bacillus strains. These strains were also confirmed for the presence of antimicrobial peptide biosynthetic genes viz., srfAA (surfactin), fenD (fengycin), spaS (subtilin), and ituC (iturin) related to secondary metabolite production (e.g., AMPs). Overall, the results suggested that application of potential bacterial strains like B. amyloliquefaciens UASBR9 not only helps in control of the biological suppression of one of the most devastating rice pathogens, M. grisea but also increases plant growth along with a reduction in application of toxic chemical pesticides.

Effects of Novel Potassium Channel Opener KR-30450 and its Metabolite KR-30818 on the Smooth, Muscle of the Guinea Pig

  • Jung, Yi-Sook;Moon, Chang-Hyun;Yoo, Sung-Eun;Shin, Hwa-Sup
    • Biomolecules & Therapeutics
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    • v.4 no.4
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    • pp.373-377
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    • 1996
  • The effect of potassium channel openers, KR-30450, KR-30818 and lemakalim have been compared against several spasmogens in guinea pig bronchi. In guinea pig bronchi, KR-30450 had a greater relaxant effect than lemakalim and KR-30818 against tone induced by histamine $10^{-5}M$ ($EC_{50}$ $\mu$M: KR-30450, 0.108$\pm$0.077; KR-30818, 0.403$\pm$0.023; lemakalim, 0.968$\pm$0.036) and prostaglandin $F_{2\alpha} 3\times10^{-6} M$ ($EC_{50}$ $\mu$M: KR-30450, 0.018$\pm$0.001; KR-30818, 0.028$\pm$0.003; lemakalim, 0.138$\pm$0.019). Relaxant effect of KR-30450 and KR-30818 were significantly reduced by 20 min pretreatment of tissues with $10^[-6}$ M glibenclamide, a selective blocker of ATP-sensitive potassium channel. Against acetylcholine-induced tone in guinea pig bronchi, however, these compounds had little effect. In summary, KR-30450 and KR-30818 showed greater relaxant effect than lemakalim in guinea pig bronchi (KR-30450>KR-30818>lemakalim). These relaxant actions are suggested to be mediated at least in part by a mechanism which involves the opening of ATP-sensitive potassium channel.

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Effect of Circadian Rhythms on the Xylene Metabolizing Enzyme Activities in Rats (Xylene 대사 효소 활성에 미치는 주.야 시차의 영향)

  • 이혜자;윤종국
    • Journal of Environmental Health Sciences
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    • v.27 no.2
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    • pp.10-16
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    • 2001
  • To evaluate an effect of circadian variation on the xylene metabolizing enzyme activities, 50% m-xylene in olive oil(0.25 $m\ell$/100g body weight) was intraperitoneally administered to the rats every other day for 6 days both in the night; 24:00 and the day; 12:00. Then animals were sacrigiced at 8hr after last injection of m-xylene. Hepatic microsomal cytochrome p450 contents were more increased both in control and xylene treated rats of night phase than those of day phase. But the activity of hepatic alcohol dehydrogenase(ADH) in control of night phase showed the similar value with that in those of day phase and xylene treated rats of day phase showed an increasing tendency of hepatic ADH activity as those of night phase showing similar activity. Furthermore, control rats of night phase than those of day phase. And by xylene treatment, enzyme activities of rats of day phase were higher tendency in rats of control but those of night phase were somewhat inhibited. Besides, xylene-treated animals of night phase showed increasing tendency of urinary methylhippuric acid concentration compared with those of day phase. On the other hand, liver weight per body weight(%), hepatic lipid peroxide content and serum xanthine oxidase activity were higher in night phase. And the activities of hepatic oxygen free radical metabolizing enzymes such as xanthine oxidase, gluthathione S-transferase, and xylene-treated rats of night phase than those of day phase. In conclusion, it can be hypothesized on the basis of the results that the accumulation rate of m-xylene intermediate metabolite, i.e. m-methylbenzaldehyde in liver tissus may be higher in night phase than in day phase and it may be responsible for higher liver toxicity in bight phase than in day phase.

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Therapeutic Effects and Adverse Drug Reactions are Affected by Icotinib Exposure and CYP2C19 and EGFR Genotypes in Chinese Non-Small Cell Lung Cancer Patients

  • Chen, Jia;Zheng, Xin;Liu, Dong-Yang;Zhao, Qian;Wu, Yi-Wen;Tan, Fen-Lai;Wang, Yin-Xiang;Jiang, Ji;Hu, Pei
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.17
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    • pp.7195-7200
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    • 2014
  • Background: The aim of this study was to evaluate how CYP2C19 affects icotinib and metabolite' exposure, and to determine whether the exposure and EGFR genotype influences survival time, tumor metastasis and adverse drug reactions. Materials and Methods: 274 NSCLC patients who accepted 125mg icotinib/t.i.d. were chosen from a phase III study. Blood samples were obtained in $672^{nd}$ ($4^{th}$ week) and $1,680^{th}$ hours ($10^{th}$ week), and plasma was used to quantify the concentration of icotinib and blood cells were sampled to check the genotypes. Clinical data were also collected at the same time, including EGFR genotypes. Plasma concentrations were assessed by HPLC-MS/MS and genotype by sequencing. All data were analyzed through SPSS 17.0 and SAS 9.2. Results: CYP 2C19 genotypes affected bio-transformation from icotinib to M24 and M26, especially in poor-metabolisers. Higher icotinib concentrations (>1000 ng/mL) not only increased patient PFS and OS but also reduced tumor metastasis. Patients with mutant EGFR experienced a higher median PFS and OS (234 and 627 days), especially those with the 19del genotype demonstrating higher PR ratio. Patients who suffered grade II skin toxicity had a higher icotinib exposure than those with grade I skin toxicity or no adverse effects. Liver toxic reactions might occur in patients with greater M20 and M23 plasma concentrations. Conclusions: CYP2C19 polymorphisms significantly affect icotinib, M24 and M26 exposure. Patients with mutant EGFR genotype and higher icotinib concentration might have increased PFS and OS and lower tumor metastasis. Liver ADR events and serious skin effects might be respectively induced by greater M20, M23 and icotinib concentrations.

Detection of Aflatoxin $M_1$ in Human and Porcine Urine and Its Risk Assessment (인축의 뇨 중 aflatoxin $M_1$의 오염분석 및 위해성 평가)

  • Kim, Hyun-Jung;Kwak, Bo-Yeon;Shon, Dong-Hwa
    • Korean Journal of Food Science and Technology
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    • v.41 no.2
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    • pp.215-219
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    • 2009
  • To conduct a risk assessment of $AFB_1$ intake, $AFM_1$, which is a metabolite of $AFB_1$ in the human and porcine urine, was determined by competitive direct ELISA (cdELISA). The detection limit of cdELISA using anti-$AFM_1$ antibody and $AFB_1$-HRP conjugate was 10 pg/mL. The recoveries of $AFM_1$ were 117-167% after the addition of $AFM_1$ in the human urine in a range of 3-100 pg/mL. 165 samples (95.5%) of those obtained from 172 persons evidenced measurable levels of urinary $AFM_1$. The detected $AFM_1$ ranges were 0-11.6 pg/mL and the average level of $AFM_1$ contamination was 2.74${\pm}$ 1.89 pg/mL. The estimated amount of $AFM_1$ excretion in the human urine was 3.97 ng/day and the estimated $AFB_1$ intake amount was 79.4 ng/day. The probable daily intake (PDI) of $AFB_1$ by the subjects was estimated to be 1.28 ng/kg bw/day, which was higher than the tolerable daily intake (TDI, 0.15 ng/kg bw/day). In the case of porcine urine, the $AFM_1$ ranged between 0.97-26.7 pg/mL and the average contaminated $AFM_1$ was 10.62${\pm}$4.39 pg/mL. The estimated amount of $AFM_1$ excretion in the porcine urine was 27.6 ng/day, and the estimated $AFB_1$ intake amount was 551 ng/day.

Plasma Metabolites Concentrations in Calves until 90 Days of Age for Estimating Genetic Ability for Milk Production Traits

  • Sasaki, O.;Yamamoto, N.;Togashi, K.;Minezawa, M.
    • Asian-Australasian Journal of Animal Sciences
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    • v.15 no.12
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    • pp.1813-1821
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    • 2002
  • The aim of this study was to identify useful secondary traits for estimating genetic ability of milk production traits. We investigated the value of using plasma metabolites concentrations. Two hundred and nineteen cattle out of 271 had only milk production traits records (G1), 33 had only metabolites records (G2), and 19 had both milk production traits and metabolites records (G3). Fifty two calves with metabolites records (G2 and G3) were born from 1992 to 1997. Forty three calves (29 females, 14 males) were used from 10 to 90 d of age and the others (3 females, 6 males) from 10 to 60 d of age. A total of 566 records of milk yield, fat yield and protein yield for 240 to 305 d on 238 heads (G1 and G2) were collected The collected blood samples were divided into three age groups: AG1, 10 to 30 d; AG2, 40 to 60 d; and AG3, 70 to 90 d. Heritabilities of milk yield, fat yield and protein yield were $0.45{\pm}0.04$, $0.50{\pm}0.04$ and $0.38{\pm}0.04$, respectively. Heritability of plasma glucose concentration at AG1 was $0.45{\pm}0.08$. Genetic correlations between plasma glucose concentration and milk yield, fat yield and protein yield were -$0.35{\pm}0.28$, $0.64{\pm}0.24$ and $0.36{\pm}0.35$, respectively. When the plasma glucose concentration at AG1 was used to estimate genetic ability of these milk production traits, reliability of milk yield of animals without milk record increased 8.2%, fat yield increased 24.2% and protein yield increased 9.5%. Heritability of plasma total cholesterol concentration at AG3 was $0.83{\pm}0.04$. Genetic correlation between plasma total cholesterol concentration and milk yield, fat yield and protein yield were $0.58{\pm}0.21$, $0.42{\pm}0.20$ and $0.45{\pm}0.22$, respectively. When the plasma total cholesterol concentration at AG3 was using to estimate genetic ability of these milk production traits, reliability of milk yield of animals without milk record increased 19.0%, fat yield increased 9.6%, and protein yield increased 13.5%. The annual genetic gain is in proportion to the reliability of selection. These results show that the plasma metabolite concentrations would be useful for improvement of genetic ability for milk production traits in the genetic improvement in herd of cows, where half of the animals selected are from a herd without its own milk record.

Effect of Antioxidants and Chelating Agents on 1,2,4-benzenetriol-induced DNA damage in HL-60 cells analysed by alkaline comet assay (항산화제 및 금속착화합물이 1,2,4-benzenetriol에 의해 유도된 HL-60 세포의 DNA 손상에 대한 보호 효과)

  • 김선진;정해원
    • Environmental Mutagens and Carcinogens
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    • v.20 no.1
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    • pp.7-13
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    • 2000
  • The mechanisms of benzene toxicity is not fully elucidated, although the metabolism of benzene is very well understood. In order to study the mechanism of benzene toxicity, we investigated DNA damage induced by benzene metabolite, 1,2,4-benzenetriol (BT) in HL-60 cells by alkaline comet assay. To investigate the mechanism of cellular DNA damage induced by BT, the cells were treated with antioxidant such as vitamin C, SOD, catalase, and chelating agent such as deferoxamine (DFO), bathocuproinedisulfonic acid (BCDS). BT induced DNA damage in dose-dependent manner at concentration between 10$\mu\textrm{m}$ and 100$\mu\textrm{m}$. The antioxidant vitamin C itself induced DNA damage at higher concentration. The DNA damage induced by BT in HL-60 cells was protected at low concentraiton of vitamin C whereas no protective effect was found at high concentration. In hibitory effect of SOD on DNA damage by BT was observed and this suggested that BT produce superoxide anion (O2-) causing DNA damage. Catalase protected BT-induced DNA damage suggesting that BT produce H2O2 during autooxidation of BT. Both Fe(II)-specific cheiating agent, deferoxamine (DFO) and Cu(I)-specific chelating agent, bathocuproinedisulfonic acid (BCDS) inhibited BT0induced DNA damage. This suggested that DNA damage was caused by active species which was produced DAN damage. This suggested that DNA damage was caused by active species which was produced by the autooxidation of BT in the presence of Cu(II) and Fe(III). These findings suggest that reactive oxygen species play an important role in the mechanism of toxicity induced by benzene metabolites.

Lysophosphatidylcholine Increases $Ca^{2+}$ Current via Activation of Protein Kinase C in Rabbit Portal Vein Smooth Muscle Cells

  • Jung, Seung-Soo;Lee, Young-Ho;Han, Sung-Sik;Kim, Young-Whan;Nam, Taik-Sang;Ahn, Duck-Sun
    • The Korean Journal of Physiology and Pharmacology
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    • v.12 no.1
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    • pp.31-35
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    • 2008
  • Lysophosphatidylcholine (LPC), a metabolite of membrane phospholipids by phospholipase $A_2$, has been considered responsible for the development of abnormal vascular reactivity during atherosclerosis. $Ca^{2+}$ influx was shown to be augmented in atherosclerotic artery which might be responsible for abnormal vascular reactivity. However, the mechanism underlying $Ca^{2+}$ influx change in atherosclerotic artery remains undetermined. The purpose of the present study was to examine the effects of LPC on L-type $Ca^{2+}$ current $(I_{Ca(L)})$ activity and to elucidate the mechanism of LPC-induced change of $I_{Ca(L)}$ in rabbit portal vein smooth muscle cells using whole cell patch clamp. Extracellular application of LPC increased $I_{Ca(L)}$ through whole test potentials, and this effect was readily reversed by washout. Steady state voltage dependency of activation or inactivation properties of $I_{Ca(L)}$ was not significantly changed by LPC. Staurosporine (100 nM) or chelerythrine $(3{\mu}M)$, which is a potent inhibitor of PKC, significantly decreased basal $I_{Ca(L)}$, and LPC-induced increase of $I_{Ca(L)}$ was significantly suppressed in the presence of PKC inhibitors. On the other hand, application of PMA, an activator of PKC, increased basal $I_{Ca(L)}$ significantly, and LPC-induced enhancement of $I_{Ca(L)}$ was abolished by pretreatment of the cells with PMA. These findings suggest that LPC increased $I_{Ca(L)}$ in vascular smooth muscle cells by a pathway that involves PKC, and that LPC-induced increase of $I_{Ca(L)}$ might be, at least in part, responsible for increased $Ca^{2+}$ influx in atherosclerotic artery.

Optimization of shoot cultures and bioactive compound accumulation in Rosa rugosa during acclimatization

  • Jang, Hae-Rim;Park, Byung-Jun;Park, Seung-A;Pee, Ok-Ja;Park, So-Young;Paek, Kee-Yoeup
    • Journal of Plant Biotechnology
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    • v.43 no.1
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    • pp.104-109
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    • 2016
  • Rosa rugosa is a medicinal, ornamental, and edible plant native to Eastern Asian countries, including Korea, Japan, and China. The aim of this study was to establish a system for biomass production and secondary metabolite accumulation during in vitro culture and acclimatization of Rosa rugosa. The highest rate of multiple shoot proliferation was achieved with $8.8{\mu}M$ benzyladenine (BA) (83.3%). However, the number of shoots (14.4 per explant) at $4.4{\mu}M$ BA was higher than that at $8.8{\mu}M$ BA. Compared to BA, a combination of thidiazuron (TDZ) and indole butyric acid (IBA) exhibited significantly lower shoot induction, with only 50.0~79.2% and 4.2~16.7% relative shoot formation, respectively. During acclimatization, shoots were sampled every week and their total phenolic contents were analyzed. Among various growth factors, fresh weight showed the most dramatic increase from the 3rd week (88.0 mg/plant) to 4th week (132.7 mg/plant). Total phenolics and flavonoids contents were the highest at $1^{st}$ week of acclimatization. Depending on developmental stages, total phenolics and flavonoids contents were higher in 1-yr-old shoots grown ex vitro than in those of older field-grown or in vitro-grown plants. Amongst different ages of field grown plants, 6-year-old plants, the oldest in this study, showed the lowest content in total phenolics.