• Toxicological Research
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• v.19 no.3
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• pp.235-240
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• 2003

The modification of CYP2E1 activity is of considerable interest because of its role in the metabolic activation of a variety of toxic chemicals. In the present studies, the time-course of changes in human CYP2E1 activities was determined after treatment with ethanol, glycerol, 4-methylpyrazole or isoniazid using intact HepG2 cells transfected by human CYP2E1. Hydroxylation of chlorzoxazone was chosen for the measurement of CYP2E1 activity. CYP2E1 protein levels were increased upon cultivation of cells in the presence of ethanol, glycerol, 4-methylpyrazole or isoniazid for 24 hr. After 24 hr cultivation, ethanol or glycerol increased CYP2E1 activities, whereas 4-methylpyrazole or isoniazid inhibited. This different effect of the chemical inducers on CYP2E1 activi-ties persisted to subsequent 24 hr. Competitive inhibition study suggested that 4-methylpyrazole or isoniazid has stronger binding affinity to CYP2E1 than ethanol or glycerol. These results demonstrate that different binding affinity of the chemical inducers to the active site of CYP2E1 plays important role in determining real CYP2E1 activity in intact cells after treatment with the chemical inducers. Present study would be helpful in precise understanding of human CYP2E1-mediated toxicity.

• Applied Chemistry for Engineering
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• v.4 no.1
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• pp.132-143
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• 1993

Aminomethyl polystyrene resins were prepared either from chloromethyl-resin(Merrifield resin) or from direct amidoalkylation of polystyrene resin. Two kinds of aminomethlyl resin were lengthened with spacer arms via sequential coupling of five ${\varepsilon}$-aminocaproic acids(ACA) respectively. In case of the resin prepared from the Merrifield resin, the amounts of free amino group of the resin were reduced by 25~30% after each coupling of ACA. But the one from direct amidoalkylation showed 3~5% loss after each coupling of ACA. 4-Nitroso-5-aminopyrazole resin was made by reacting ACA spacer arm resin, which was made from direct amidoalkylated resin, with 5-phenyl-7-methylpyrazole [4,3-c][1,2,4]oxadiazin-3-one. Several polymeric active esters of N-blocked amino acids were prepared from the 4-nitroso-5-aminopyrazole bound resins. In anchoring step of the amino acid derivatives on the resin, no substantial effect of bulkiness was found. 4-Nitroso-5-aminopyrazole bound active ester resins were found to be very reactive in N-acylation, The resulting peptides were obtained with 90~95% yield and characterized by NMR and other physical methods.

• Toxicological Research
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• v.14 no.4
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• pp.557-562
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• 1998

Allyl alcohol is metabolized in the liver through two steps, first to reactive acrolein by alcohol dehydrogenase (ADH), subsequently to acrylic acid by aldehyde dehydrogenase (ALDH). Since ethanol could compete the same enzymes to be metabolized in the liver, we have determined the plasma concentrations of allyl alcohol and ethanol followed by combined treatment. Pretreatment of rats with 2g/kg ethanol followed by ip administration of 40mg/kg allyl alcohol increased the lethality significantly. Determination of in vivo blood concentrations revealed that ethanol pretreatment caused the apparent decrease in allyl alcohol clearance, whereas acetaldehyde level in blood increased significantly by allyl alcohol treatment, as determined by head space GC analysis. Treatment of 4-methylpyrazole, an inhibitor of ADH, delayed allyl alcohol elimination significantly and reduced its lethality. Collectively, these findings suggested that reduction of allyl alcohol clearance in the presence oj ethanol was mediated through ADH competitive inhibition.

• Toxicological Research
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• v.14 no.2
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• pp.157-161
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• 1998

The mechanism of active aldehyde-induced liver disease and the enzymatic basis of detoxification were investigated using normal rat liver cell, Ac2F. Aliphatic alcohols including l-decyl alcohol, l-nonanol, l-heptanol, l-hexanol, l-propanol and allyl alcohol exerted a dose- and time-de-pendent toxicity to Ac2F cells. The extent of their toxicities in buthionine sulfoximine (inhibitor of glutathione synthesis) pretreated cells was greater than in pargyline (inhibitor of aldehyde dehydrogenase, ALDH). On the other hand, the toxicity of these alcohols were not affected by 4-methylpyrazole (inhibitor of alcohol dehydrogenase, ADH). These results suggest that the contents of glutathione (GSH) seems to be very important in protecting the cells from toxicants such as aliphatic alcohols.

• Bulletin of the Korean Chemical Society
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• v.30 no.5
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• pp.1035-1038
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• 2009

Phytochemical investigation of the methanolic extract of Diospyros kaki leaves led to the isolation of osmanthuside H (1) and a new phenol glycoside, named gamnamoside [4-(3-hydroxypropyl)-2-methoxyphenol $\beta$-D-apiofuranosyl( 1 $\rightarrow$ 6)$\beta$-D-glucopyranoside] (2) along with (-) catechin (3) through a series of reversed phase column chromatography and preparative C18 HPLC. The structures of the isolates were determined by spectroscopic methods including IR, UV, HRTOFMS, and 2D NMR. Compounds 1, 2, and 3, showed good inhibitory activities ($IC_{50}$) of 175.4, 94.4, and 126.6 ${\mu}g/mL$ respectively, whereas a reversible ADH inhibitor, 4-methylpyrazole, showed the $IC_{50}$ of 326.6 ${\mu}g/mL$ against alcohol dehydrogenase (ADH).

• The Korean Journal of Pesticide Science
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• v.5 no.1
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• pp.36-45
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• 2001

This study was conducted to search new target enzymes of novel herbicide candidate. Total of 107 biochemical inhibitors reported to inhibit over than 100 different plant enzymes were purchased from commercial chemical companies. 15 inhibitors and 34 enzymes were selected by germination assay, seedling assay, wheat leaf disc assay, and whole plant assay. Among them, seven compounds of purine, phehyl-hydrazine, o-phenanthroline, oleylamine, dicyclohexylcarbodiimide, 7,8-benzoquinoline, and aminooxyacetic acid showed high herbicidal activity in the whole plant assay under greenhouse while 7,8-benzoquinone, 8-hydroxyquinoline, 2,2'-dipyridyl, and o-phenanthroline inhibited seed germination of barnyardgrass, rice, and tomato at concentrations of 1.25 to $5{\mu}M$. The compounds of 7,8-benzoquinoline, chlorpromazine, cyanuric fluoride, 4-methylpyrazole, oleylamine, tranylcypromine, and trifluoperazine inhibited the growth of cyanobacteria at 30 to $100{\mu}M$. The compounds of dicyclohexylcarbodiimide and chlorpromazine exhibited whitening effect on tile wheat leaf disc at $100{\mu}M$. These results suggest that the plant-specific enzyme inhibitors which have biological activities may supply the target enzyme for developing new herbicide candidate.

• Molecules and Cells
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• v.38 no.11
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• pp.998-1006
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• 2015

Retinols are metabolized into retinoic acids by alcohol dehydrogenase (ADH) and retinaldehyde dehydrogenase (Raldh). However, their roles have yet to be clarified in hepatitis despite enriched retinols in hepatic stellate cells (HSCs). Therefore, we investigated the effects of retinols on Concanavalin A (Con A)-mediated hepatitis. Con A was injected into wild type (WT), Raldh1 knockout ($Raldh1^{-/-}$), $CCL2^{-/-}$ and $CCR2^{-/-}$ mice. For migration study of regulatory T cells (Tregs), we used in vivo and ex vivo adoptive transfer systems. Blockade of retinol metabolism in mice given 4-methylpyrazole, an inhibitor of ADH, and ablated Raldh1 gene manifested increased migration of Tregs, eventually protected against Con A-mediated hepatitis by decreasing interferon-${\gamma}$ in T cells. Moreover, interferon-${\gamma}$ treatment increased the expression of ADH3 and Raldh1, but it suppressed that of CCL2 and IL-6 in HSCs. However, the expression of CCL2 and IL-6 was inversely increased upon the pharmacologic or genetic ablation of ADH3 and Raldh1 in HSCs. Indeed, IL-6 treatment increased CCR2 expression of Tregs. In migration assay, ablated CCR2 in Tregs showed reduced migration to HSCs. In adoptive transfer of Tregs in vivo and ex vivo, Raldh1-deficient mice showed more increased migration of Tregs than WT mice. Furthermore, inhibited retinol metabolism increased survival rate (75%) compared with that of the controls (25%) in Con A-induced hepatitis. These results suggest that blockade of retinol metabolism protects against acute liver injury by increased Treg migration, and it may represent a novel therapeutic strategy to control T cell-mediated acute hepatitis.

• Biomolecules & Therapeutics
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• v.20 no.5
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• pp.492-498
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• 2012

Phytochemicals have been known to exhibit potent antioxidant activity. This study examined cytoprotective effects of phytochemicals including quercetin, catechin, caffeic acid, and phytic acid against oxidative damage in SK-Hep-1 cells induced by the oxidative and non-oxidative metabolism of ethanol. Exposure of the cells to excess ethanol resulted in a significant increase in cytotoxicity, reactive oxygen species (ROS) production, lipid hydroperoxide (LPO), and antioxidant enzyme activity. Excess ethanol also caused a reduction in mitochondrial membrane potential (MMP) and the quantity of reduced glutathione (GSH). Co-treatment of cells with ethanol and quercetin, catechin, caffeic acid and phytic acid significantly inhibited oxidative ethanol metabolism-induced cytotoxicity by blocking ROS production. When the cells were treated with ethanol after pretreatment of 4-methylpyrazole (4-MP), increased cytotoxicity, ROS production, antioxidant enzyme activity, and loss of MMP were observed. The addition of quercetin, catechin, caffeic acid and phytic acid to these cells showed suppression of non-oxidative ethanol metabolism-induced cytotoxicity, similar to oxidative ethanol metabolism. These results suggest that quercetin, catechin, caffeic acid and phytic acid have protective effects against ethanol metabolism-induced oxidative insult in SK-Hep-1 cells by blocking ROS production and elevating antioxidant potentials.

• The Korean Journal of Pesticide Science
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• v.3 no.1
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• pp.96-101
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• 1999

3-Trifluoromethylpyrazoles and 4-benzenecarbinolpyrazoles were prepared by the new synthetic methodologies, and their herbicidal effects were tested (in vivo) in the upland conditions and in the flooded paddy conditions for the purpose of the development of new herbicides. In upland conditions, most of the pyrazoles showed weak herbicidal effects at 4 kg/ha dosage in the post-emergence test, while no herbicidal effects in the pre-emergence test. In the flooded paddy conditions, some of the pyrazoles showed good herbicidal effects at a rate of 4 kg/ha, especially, 3-trifluoromethyl-4-(4-methoxybenzoyl)pyrazole showed the best herbicidal activity with good selectivity between rice and weeds. But other derivatives substituted with electron-donating groups such as dior trimethoxy and sulfides, and 4-benzenecarbinolpyrazoles showed weak herbicidal effects.

• Korean Journal of Weed Science
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• v.16 no.4
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• pp.317-326
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• 1996

To know whether pyrazosulfuron-ethyl(PYR) and imazaquin(IMA), known as a acetolactate synthase(ALS) inhibitors, have a same herbicidal action pattern in rice(Oryza sativa) or barnyardgrass (Echinochloa crus-galli), an inhibition pattern and a response characteristics in combination with dymron or butachlor were investigated. In contrast to the phytotoxicity of rice treated with IMA, the one treated with PYR was completely tended to be recovered after 25 days after treatment. Safening effect of dymron against PYR was effectively developed to transplanted-rice, while such an effect was not shown in combination with IMA. In combination with PYR and butachlor, antagonistic effect was observed in both simultaneous or sequential treatment on bamyardgrass, however, additive effect was rather shown in combination with IMA and its activity was dominantly dependent on the first applied compound. $I_{50}$ of PYR and IMA on the ALS extracted from barnyardgrass was $4{\times}10^{-7}$M and $2.8{\times}10^{-6})$M, respectively. Butachlor did not affect their activities on ALS in vitro. These results suggest that PYR and IMA might have a different action each other in the pathway to a final herbicidal activity even though their primary action site is ALS.