• Archives of Pharmacal Research
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• v.28 no.3
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• pp.249-268
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• 2005

Drug metabolizing enzymes (DMEs) play central roles in the metabolism, elimination and detoxification of xenobiotics and drugs introduced into the human body. Most of the tissues and organs in our body are well equipped with diverse and various DMEs including phase I, phase II metabolizing enzymes and phase III transporters, which are present in abundance either at the basal unstimulated level, and/or are inducible at elevated level after exposure to xenobiotics. Recently, many important advances have been made in the mechanisms that regulate the expression of these drug metabolism genes. Various nuclear receptors including the aryl hydrocarbon receptor (AhR), orphan nuclear receptors, and nuclear factor-erythoroid 2 p45-related factor 2 (Nrf2) have been shown to be the key mediators of drug-induced changes in phase I, phase II metabolizing enzymes as well as phase III transporters involved in efflux mechanisms. For instance, the expression of CYP1 genes can be induced by AhR, which dimerizes with the AhR nuclear translocator (Arnt) , in response to many polycyclic aromatic hydrocarbon (PAHs). Similarly, the steroid family of orphan nuclear receptors, the constitutive androstane receptor (CAR) and pregnane X receptor (PXR), both heterodimerize with the ret-inoid X receptor (RXR), are shown to transcriptionally activate the promoters of CYP2B and CYP3A gene expression by xenobiotics such as phenobarbital-like compounds (CAR) and dexamethasone and rifampin-type of agents (PXR). The peroxisome proliferator activated receptor (PPAR), which is one of the first characterized members of the nuclear hormone receptor, also dimerizes with RXR and has been shown to be activated by lipid lowering agent fib rate-type of compounds leading to transcriptional activation of the promoters on CYP4A gene. CYP7A was recognized as the first target gene of the liver X receptor (LXR), in which the elimination of cholesterol depends on CYP7A. Farnesoid X receptor (FXR) was identified as a bile acid receptor, and its activation results in the inhibition of hepatic acid biosynthesis and increased transport of bile acids from intestinal lumen to the liver, and CYP7A is one of its target genes. The transcriptional activation by these receptors upon binding to the promoters located at the 5-flanking region of these GYP genes generally leads to the induction of their mRNA gene expression. The physiological and the pharmacological implications of common partner of RXR for CAR, PXR, PPAR, LXR and FXR receptors largely remain unknown and are under intense investigations. For the phase II DMEs, phase II gene inducers such as the phenolic compounds butylated hydroxyanisol (BHA), tert-butylhydroquinone (tBHQ), green tea polyphenol (GTP), (-)-epigallocatechin-3-gallate (EGCG) and the isothiocyanates (PEITC, sul­foraphane) generally appear to be electrophiles. They generally possess electrophilic-medi­ated stress response, resulting in the activation of bZIP transcription factors Nrf2 which dimerizes with Mafs and binds to the antioxidant/electrophile response element (ARE/EpRE) promoter, which is located in many phase II DMEs as well as many cellular defensive enzymes such as heme oxygenase-1 (HO-1), with the subsequent induction of the expression of these genes. Phase III transporters, for example, P-glycoprotein (P-gp), multidrug resistance-associated proteins (MRPs), and organic anion transporting polypeptide 2 (OATP2) are expressed in many tissues such as the liver, intestine, kidney, and brain, and play crucial roles in drug absorption, distribution, and excretion. The orphan nuclear receptors PXR and GAR have been shown to be involved in the regulation of these transporters. Along with phase I and phase II enzyme induction, pretreatment with several kinds of inducers has been shown to alter the expression of phase III transporters, and alter the excretion of xenobiotics, which implies that phase III transporters may also be similarly regulated in a coordinated fashion, and provides an important mean to protect the body from xenobiotics insults. It appears that in general, exposure to phase I, phase II and phase III gene inducers may trigger cellular 'stress' response leading to the increase in their gene expression, which ultimately enhance the elimination and clearance of these xenobiotics and/or other 'cellular stresses' including harmful reactive intermediates such as reactive oxygen species (ROS), so that the body will remove the 'stress' expeditiously. Consequently, this homeostatic response of the body plays a central role in the protection of the body against 'environmental' insults such as those elicited by exposure to xenobiotics.

• Korean Journal of Weed Science
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• v.30 no.2
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• pp.122-134
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• 2010

We investigated the levels of resistance and accumulation of terapyrroles, reactive oxygen species, lipid peroxidation, and antioxidative enzymes for reasons of growth reduction in herbicide-transgenic rice overexpressing Myxococcus xanthus, Arabidopsis thaliana, and human protoporphyrinogen oxidase (Protox) genes. The transgenic rice overexpressing M. xanthus (MX, MX1, PX), A. thaliana (AP31, AP36, AP37), and human (H45, H48, H49) Protox genes showed 43~65, 41~72 and 17~70-fold more resistance to oxyfluorfen, respectively, than the wild type. Among transgenic rice lines overexpressing Protox genes, several lines showed normal growth compared with the wild type, but several lines showed in reduction of plant height and shoot fresh weight under different light conditions. However, reduction of plant height of AP37 was much higher than other lines for the experimental period. On the other hand, the reduction of plant height and shoot fresh weight in the transgenic rice was higher in high light condition than in low light condition. Enhanced levels of Proto IX were observed in transgenic lines AP31, AP37, and H48 at 7 days after seeding (DAS) and transgenic lines PX, AP37, and H48 at 14 DAS relative to wild type. There were no differences in Mg-Proto IX of transgenic lines except for H41 and H48 and Mg-Proto IX monomethyl ester of transgenic lines except for MX, MX1, and PX. Although accumulation of tetrapyrrole intermediates was observed in transgenic lines, their tetrapyrrole accumulation levels were not enough to inhibit growth of transgenic rice. There were no differences in reactive oxygen species, MDA, ALA synthesizing capacity, and chlorophyll between transgenic lines and wild type indicating that accumulated tetrapyrrole intermediate were apparently not high enough to inhibit growth of transgenic rice. Therefore, the growth reduction in certain transgenic lines may not be caused by a single factor such as Proto IX, but by interaction of many other factors.

• Journal of Korean Society of Environmental Engineers
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• v.27 no.7
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• pp.746-752
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• 2005

In this study, the effect of reaction parameters including reaction temperature, time, and pressure on sludge degradation and conversion to intermediates such as organic acids were investigated at low critical wet air oxidation(LC-WAO) conditions. Degradation pathways and a modified kinetic model in LC-WAO were proposed and the kinetics model predictions were compared with experimental data under various conditions. Results in the batch experiments showed that reaction temperature directly affected the thermal hydrolysis reaction rather than oxidation reaction. The efficiencies of sludge degradation and organic acid formation increased with the increase of the reaction temperature and time. The removal of SS at $180^{\circ}C$, $200^{\circ}C$, $220^{\circ}C$ and $240^{\circ}C$ of reaction temperatures and 10 min of reaction time were 52.6%, 68.3%, 72.6%, and 74.4%, respectively, indicating that most organic suspended solids were liquified at early stage of reaction. At $180^{\circ}C$, $200^{\circ}C$, $220^{\circ}C$ and $240^{\circ}C$ of reaction temperatures and 40 min of reaction time, the amounts of organic acids formed from 1 g of sludge were 93.5 mg/g SS, 116.4 mg/g SS, 113.6 mg/g SS, and 123.8 mg/g SS, respectively, and the amounts of acetic acid from 1 g of sludge were 24.5 mg/g SS, 65.5 mg/g SS, 88.1 mg/g SS, and 121.5 mg/g SS, respectively. This suggested that the formation of sludge to organic acids as well as the conversion of organic acids to acetic acid increased with reaction temperature. Based on the experimental results, a modified kinetic model was suggested for the liquefaction reaction of sludge and the formation of organic acids. The kinetic model predicted an increase in kinetic parameters $k_1$ (liquefaction of organic compounds), $k_2$ (formation of organic acids to intermediate), $k_3$ (final degradation of intermediate), and $k_4$ (final degradation of organic acids) with reaction temperature. This indicated that the liquefaction of organic solid materials and the formation of organic acids increase according to reaction temperature. The calculated activation energy for reaction kinetic constants were 20.7 kJ/mol, 12.3 kJ/mol, 28.4 kJ/mol, and 54.4 kJ/mol, respectively, leading to a conclusion that not thermal hydrolysis but oxidation reaction is the rate-limiting step.

• Korean Chemical Engineering Research
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• v.48 no.2
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• pp.259-267
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• 2010

The catalytic wet oxidations of the wastewater containing azo dye Reactive Black 5(RB5) with heterogeneous catalyst of CuO have been carried out to investigate the effects of temperature($190{\sim}230^{\circ}C$) and catalyst concentration(0.00~0.20 g/l) on the removals of colour and total organic carbon TOC. The wastewater colour was measured with spectrophotometer, and the oxidation rate was estimated with TOC. About 90% of colour was removed during 120 min in thermal degradation of the RB5 wastewater at $230^{\circ}C$, while TOC was not removed at all. As increasing reaction temperature and catalyst concentration, the removal rates of colour and TOC increased in the catalytic wet oxidations of RB5 wastewater. The effects of catalyst were already considerable even at 0.01 g CuO/l, while the removal rates of colour and TOC increased negligibly with increasing the catalyst concentration above 0.05 g CuO/l. The initial destruction rates of the wastewater colour have shown the first-order kinetics with respect to the wastewater colour. TOC changes during catalytic wet oxidations have been well described with the global model, in which the easily degradable TOC was distinguished from non-degradable TOC of the wastewater. The impacts of reaction temperature on the destruction rate of the wastewater colour and TOC could be described with Arrhenius relationship. Activation energies of the colour removal reaction in thermal degradation, wet oxidation, and catalytic wet oxidation(0.20 g CuO/l) of the RB5 wastewater were 108.4, 78.3 and 74.1 kJ/mol, respectively. The selectivity of wastewater TOC into the non-degradable intermediates relative to the end products in the catalytic wet oxidations of RB5 wastewater was higher compared to that in phenol wet oxidations.

• Korean Journal of Microbiology
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• v.40 no.1
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• pp.29-36
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• 2004

The purpose of this work was to investigate the relationships between acrylamide degradation by Pseudomonas sp. JK-7 and several relevant physicochemical environment parameters. In initial experiments, the bacterial culture, strain JK-7 isolated from paddy soil sample was developed to grow aerobically with acrylamide as the sole source of carbon and nitrogen. The bacterium was identified as genus Pseudomonas in the basis of use BIOLOG test, and designated as Pseudomunas sp. JK-7. Strain JK-7 could degrade 50 mM acrylamide completely within 72 hours of incubation. Major intermediates resulting from acrylamide degradation were not detected with the HPLC methodology except acrylic acid which appeared to accumulate transiently in the growth medium. The pH increased from 7.0 to 8.7 with complete degradation of the initial 50 mM acrylamide within 72 hours of incubation. pH control in the range of 5 to 9 influenced the growth of JK-7 and acrylamide degradation, whereas it was not examined the growth and degradation at pH 3 or pH 11, respectively. The effect of supplemented carbons (e.g., glucose, fructose, citrate, succinate) on the acrylamide degradation by the test culture of JK-7 was evaluated. The results indicated that the addition of carbons accelerated the bacterial growth and acrylamide degradation compared to those in the absence of supplemented carbons. The effect of supplemented nitrogens on the degradation was monitored. Increasing concentrations of yeast extract resulted in higher growth yield, based on the turbidity measurement, and complete degradation of acrylamide. However, acrylamide degradation was essentially uninfluenced by the addition of $(NH_{4})_{2}SO_{4}$, $NH_4Cl$ or urea. Addition of $AgNO_3$, $CuSO_4$ or $HgCl_2$ except $ZnSO_4$ in the test culture inhibited the degradation of acrylamide and growth of JK-7.

• Journal of Nutrition and Health
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• v.46 no.2
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• pp.109-118
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• 2013

Ultraviolet (UV) irradiation reduces epidermal hydration, which is paralleled by the reduction of natural moisturizing factors (NMFs). Of various NMFs, free amino acids (AAs) are major constituents generated by filaggrin degradation. In this study, we attempted to determine whether dietary supplementation of royal jelly (RJ) in UV-irradiated mice can alters epidermal levels of hydration, filaggrins, and free AAs as well as of peptidylarginine deiminase-3 (PAD3), an enzyme involved in filaggrin degradation processes. Albino hairless mice were fed either a control diet (group UV+: UV irradiated control) or diets with 1% RJ harvested from different areas in Korea (groups RJ1, RJ2, and RJ3) or imported from China (group RJ4) for six weeks in parallel with UV irradiation. A normal control group (group UV-) was fed a control diet without UV irradiation for six weeks. Reduced epidermal levels of hydration, total filaggrins, and PAD3 were observed in group UV+; in group RJ1, these levels were increased to a level similar to that of group UV-. In addition, profilaggrins, two repeat intermediates (2RI), a precursor with two filaggrin repeats, and filaggrin were increased. Although no alteration of AAs was observed in any of the groups, and glutamate and serine, major AAs of NMF in group RJ1 were higher than in group UV+. Despite the increased levels of PAD3, epidermal levels of hydration, filaggrins, glutamate, and serine in groups RJ2, RJ3, and RJ4 were similar to those in group UV+. Dietary supplementation of RJ1 improves epidermal hydration in parallel with enhanced expression and degradation of filaggrin, but not by increased protein expression of PAD3, along with increased generation of glutamate and serine.

• Korean Chemical Engineering Research
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• v.59 no.4
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• pp.584-595
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• 2021

In this study, the correlation between operating stages of waste air-treating system composed of two alternatively-operating UV/photocatalytic reactors, and the deactivation of photocatalyst used in each operating stage, was investigated by instrumental analysis thereon. The repeated deactivation and subsequent re-generation of photocatalyst used in the waste air treating system of previous investigation performed by Lee and Lim (Korean Chem. Eng. Research, 59(4), 574-583(2021)), were characterized on virgin photocatalyst-carrying porous SiO₂ media (A4), used photocatalyst-carrying porous SiO₂ media (A1, A2 and A3) collected from the corresponding photocatalytic reactor upon 1^st, 2^nd, and 3^rd run, respectively, regenerated photocatalyst-carrying porous SiO₂ media upon 1 time-run (AD1) and 3 times regenerated photocatalyst-carrying porous SiO₂ media upon 3 time-runs (AD3) by instrumental analysis including BET analysis, SEM, XPS, SEM-EDS and FT-IR. As a result, the proper regeneration-temperature for deactivated photocatalyst to be regenerated several times (more than 3 times), was suggested below 200 ℃. Such temperature of deactivated photocatalyst-regeneration was almost consistent to the one, according to BET analysis, at which tiny nano-pores blocked by adsorbed ethanol-oxidative and degraded intermediates (AEODI), were regenerated to be reopened through almost complete mineralization of AEODI. In particular, the results of XPS analysis indicated an incurrence of insignificant deactivation of photocatalysis upon 1^st run of UV/photocatalytic reactor (A or C) of the previous investigation. In addition, the results of XPS analysis were consistent with the experimental results of the previous investigation in that 1) deactivation of photocatalyst incurred during 2^nd run of the UV/photocatalytic reactor (A or C) resulted in decreased removal efficiency, by ca. 5% and 5%, of ethanol and hydrogen sulfide, respectively, compared with its 1^st run; 2) there was insignificant difference between the removal efficiencies of its 2^nd run and 3^rd run. Furthermore, the removal efficiencies of ethanol and hydrogen sulfide for hypothetical 4^th run of photocatalytic reactor in the previous investigation, using AD3, were expected to decrease, compared with its 3^rd run, by much more than those for 2^nd run in the previous investigation did, compared with its 1^st run.

• The Korean Journal of Pharmacology
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• v.32 no.3
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• pp.407-416
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• 1996

The reactive intermediates formed during the metabolism of therapeutic agents, toxicants and carcinogens by cytochromes P450 are frequently capable of covalently binding to tissue macromolecules and causing tissue damage. It has been shown that YH439, a congener of malotilate, is effective in suppressing hepatic P450 2E1 expression. The present study was designed to further establish the mechanistic basis of YH439 protection against toxicant by assessing its effects against chemical-mediated potentiated hepatotoxicity. Retinoyl palmitate (Vit-A) pretreatment of rats for 7 days substantially enhanced carbon tetrachloride hepatotoxicity, as supported by an ${\sim}5-fold$ increase in serum alanine aminotransferase (ALT) activity, as compared to $CCl_4$ treatment alone. The elevation of ALT activity due to Vit-A was completely blocked by the treatment of $GdCl_3$ a selective inhibitor of Kupffer cell activity. Concomitant pretreatment of rats with both YH439 and Vit-A resulted in a 94% decrease in Vit-A-potentiated $CCl_4$ hepatotoxicity. YH439 was also effective against propyl sulfide-potentiated $CCl_4-induced$ hepatotoxicity. Whereas propyl sulfide (50 mg/kg, 7d) enhanced $CCl_4-induced$ hepatotoxicity by >5-fold, relative to $CCl_4$ treatment alone, concomitant treatment of animals with both propyl sulfide and YH439 at the doses of 100 and 200 mg/kg prevented propyl sulfide-potentiated $CCl_4$ hepatotoxicity by 35% and 90%, respectively. Allyl sulfide, a suppressant of hepatic P450 2E1 expression, completely blocked the propyl sulfide-enhanced hepatotoxicity, indicating that propyl sulfide potentiation of $CCl_4$ hepatotoxicity was highly associated with the expression of P450 2E1 and that YH439 blocked the propyl sulfide-enhanced hepatotoxicity through modulation of P450 2E1 levels. Propyl sulfide- and $CCl_4-induced$ stimulation of lipid peroxidation was also suppressed by YH439 in a dose-related manner, as supported by decreases in malonedialdehyde production. The role of P450 2E1 induction in the potentiation of $CCl_4$ toxicity and the effects of YH439 were further evaluated using pyridine as a P450 2E1 inducer. Pyridine pretreatment substantially enhanced the $CCl_4$ hepatotoicity by 23-fold, relative to $CCl_4$ alone. YH439, however, failed to reduce the pyridine-potentiated toxicity, suggesting that the other form(s) of cytochroms P450 inducible by pyridine, but not suppressible by YH439 treatment, may play a role in potentiating $CCl_4-induced$ hepatotoxicity. YH439 was capable of blocking cadmium chloride-induced liver toxicity in mice. These results demonstrated that YH439 efficiently blocks Vit-A-enhanced hepatotoxiciy through Kupffer cell inactivation and that the suppression of P450 2E1 expression by YH439 is highly associated with blocking of propyl sulfide-mediated hepatotoxicity.

• Journal of Korean Society of Forest Science
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• v.86 no.3
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• pp.378-390
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• 1997

Ten total populations of Korean fir (Abies koreana Wilson) and Manshurian fir [A. nephrolepis (Traut.) Maxim.] were sampled from south Korea to investigate patterns of intraspecific variation in these species and to evaluate a recognition of the two species. Principal components analysis and cluster analysis were performed both on seed-cone data and on needle morphology data. The characters that contributed most to the separation between A. koreana and A. nephrolepis along three principal components axis were leaf width, length of seed, width of seed wing, length of seed wing, cone width, width of scale, and length of bract tip, but these characters were not diagnostic because of overlap in reality. Therefore, all these characters were not reliable in distinguishing these two taxa including bract position (exerted and recurved vs. exerted and straight). The individuals of A. koreana from Mt. Chi-ri appeared quite unique probably on account of its larger cone size and longer scale tip, while those from Mt. Hal-la of A. koreana were generally distinct from others in terms of their larger seed and seed wing and longer scale width. The Mt. Duk-yu specimens of A. korecana appeared somewhat smaller but more data were needed due to the small sampling size. Generally, the gradual clinal geographic trends made evident by the position of resin ducts in leaves of A. koreana can be detected. The southern populations, Mt. Hal-la (an insular population) were generally distinct from the northern populations (Mt. Chi-ri, Mt. Ga-ya and Mt. Duk-yu) in terms of their position of resin duct (medial, within mesophyll vs marginal, close to epidermis : 100% vs 75 or 50%). Although no sharp boundary separating these two species could be detected based on cone and needle morphology, the observed clinal pattern was distinct in northern populations of A. koreana and southern population of A. nephrnlepis. In a preceding study of the flavonoids variation of 20 species in eastern Asia, flavanone (5-deoxyflavanone) was found to be characteristic of A. faxoniana Rehder et Wilson, A. georgei Orr of China and A. koreana of Korea. A. faxoniana, which is assumed to be primitive species, has position of resin duct relative to both the medial and the marginal, while A. georgei and A. koreana are identified by marginal position of resin duct. With respect of foliar flavonoids chemistry, A. koreana was distinct from A. nephrolepis : the southmost samples (Mt. Hal-la and Mt. Chi-ri) contained additional flavonoids derivatives (mainly flavanone) that were not found in the northmost samples of A. nephrolepis except a few individuals from Mts. Seo-rak and Tae-bak populations of Kwang-won province. The presence of A. koreana type flavonoids in two Chinese species suggested that position of resin duct may be a phyletic character. Abies koreana including two Chinese taxa, exhibited the most elaborate and specialized flavonoids profile within the Abies in eastern Asia. Contrary to our initial expectations, the apparent intermediates between A. nephrolepis and A. koreana in Duk-yu and Ga-ya mountains were found. The pattern of variation on position of resin duct and flavonoids chemistry in these populations of A. kareana suggested that genetic interchange or natural hybridization had occurred between these two species. The evidence needed to resolve the status of this taxon is still inconclusive in our opinion until intermediate individuals from Mts. Duk-yu and Ga-ya show indication of hybridization between the two species.