• Proceedings of the Korean Society of Applied Pharmacology
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• 1998.11a
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• pp.191-191
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• 1998

It has been hypothesized that formation of oxygen-derived free radicals may play an important part in ischemically induced tissue injury. In this study, the effects of vitamin C treatment on hepatic reperfusion model were investigated. Livers isolated from 18 hrs fasted rats were subjected to low flow hypoxia (1 $m\ell$/g liver/min, for 45min) followed by reoxygenation (for 30min). The perfusion medium used was Krebs-Henseleit bicarbonate buffer (KHBB, pH 7.4) and vitamin C (0.25, 0.5, 1.0 and 2.0 mM) was added to perfusate. 7-Ethoxycoumarin was used as substrate of phase and metbolism. After hypoxia oxygen consumption significantly dropped but vitamin C 0.25, 0.5 and 1.0 mM treatments restored oxygen consumption to the level of control group. LDH and lipid peroxidation were not changed in all experimental groups. Oxidation, phase metabolism, significantly decreased following hypoxia but improved during reoxygenation. Vitamin C 0.25 mM treatment significantly improved the oxidation of 7-ethoxycoumarin during hypoxia and reoxygenation, but the oxidation significantly decreased by vitamin C 2.0 mM treatment. Similarly, sulfate conjugation decreased in hypoxic group, but this decrease was inhibited by vitamin C 0.25, 0.5 and 1.0 mM treatments. Our findings suggest that hypoxia/reoxygenation diminishes hepatic drug metabolizing function, vitamin C at concentration of 0.25-1.0 mM ameliorates but at higher concentration aggravates these hypoxia/reoxygenation-induced changes.

• Archives of Pharmacal Research
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• v.26 no.12
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• pp.1079-1086
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• 2003

The aim of this study was to investigate the effect of trauma on cytochrome P450 (CYP) gene expression and to determine the role of Kupffer cells in trauma-induced alteration of CYP isozymes. Rats underwent closed femur fracture (FFx) with associated soft-tissue injury under anesthesia. To deplete Kupffer cells in vivo, gadolinium chloride ($GdCl_3$) was intravenously injected at 7.5 mg/kg body wt., 1 and 2 days prior to FFx surgery. At 72 h of FFx, liver tissues were isolated to determine the mRNA and protein expression of CYP isozymes and NADPH-P450 reductase by reverse transcription-polymerase chain reaction and Western immunoblotting, respectively. In addition, the mRNA levels of tumor necrosis factor alpha (TNF-$\alpha$), inducible nitric oxide synthase (iNOS) and heme oxygenase-1 (HO-1) were evaluated. FFx increased the mRNA level of CYP1A1; an increase that was not prevented by $GdCl_3$. There were no significant differences in the mRNA expression of CYP1A2, 2B1 and 2E1 among any of the experimental groups. The protein levels of CYP2B1 and 2E1 were significantly decreased by FFx; a decrease that was not prevented by $GdCl_3$ treatment. The gene expression of NADPH-P450 reductase was unchanged by FFx. FFx significantly increased the expression of TNF-$\alpha$ mRNA; an increase that was attenuated by $GdCl_3$. The mRNA expression of HO-1 was increased by FFx, but not by $GdCl_3$ . Our findings suggest that FFx differentially regulates the expression of CYP isozyme through Kupffer cell-independent mechanisms.

• Korean Journal of Veterinary Research
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• v.43 no.2
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• pp.171-180
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• 2003

Certain hexavalent chromium compounds when administered via inhalation have the potential to induce lung injury in human and experimental animals. In present study, the inhalation effect of hexavalent chromium on morphological change and weight change of rat organ were investigated. Rats were exposed to hexavalent chromium ($Na_2CrO_4{\cdot}4H_2O$) at concentration of $0.36mg/m^3$ (group 1), $1.8mg/m^3$ (group 2), ascorbic acid and $1.8mg/m^3$ (group 3) and filtered air (group 0, control group) for I week, 2 weeks and 3 weeks. The weight of lung and kidney in group 2 and group 3 significantly higher than in control group at same exposure period. The epithilial cells of bronchiole in group 1, 2, 3 were more flatten than group 0. In the lung, the number of macrophage was significantly increased and morphologically changed macrophages were observed in group 1, 2, 3. The morphological change of the lung did not significant between group 2 and group 3, however, in group 1 was milder than in group 2 and group 3. The severity of morphological change were depend on exposure period in the lung. The morphological changes by hexavalent chromium of the liver and kidney were also observed These results suggest that inhalation of hexavalent chromium effects on not only respiratory organ, but also the liver and the kidney via blood stream.

• Journal of the Korean Society of Food Science and Nutrition
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• v.36 no.3
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• pp.291-297
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• 2007

This study was conducted to investigate the hepatic detoxification effect of microcluster-water (McW). Animal experiments were divided into 4 groups: distilled water intake group (DC), distilled water intake-bromobenzene treated group (DB), McW intake group (MC), and McW intake-bromobenzene treated group (MB). There were no significant differences in alanine aminotransferase and aspartate aminotransferase activities between DC and MC groups, but the activities in MB group were significantly (p<0.05) lower than those in DB group. No apparent changes of aniline hydrolase activity were shown in all experimental groups, while glutathione S-transferase activity in MC and MB groups was higher than that in DC and DB, respectively. The content of hepatic lipid peroxide in DC group was similar to that of MC group. In addition, the contents in DB and MB groups were significantly (p<0.05) increased than that of DC group. The increasing rate in MB group was lower than that of DB group. Also, the electron donating activity of McW was significantly (p<0.05) higher than that of distilled water. From these results, it could be suggested that McW has the possibility of having detoxification effect of bromobenzene induced hepatic injury by increasing glutathione S-transferase, which is known as a kind of hepatiic detoxification enzyme.

• Biomedical Science Letters
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• v.3 no.2
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• pp.151-160
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• 1997

This study was planned to evaluate the urinary ascorbic acid as a new biological marker for the intoxication of cadmium, which could possibly be driven by its increased utilization and environmental pollution. In order to meet this goal, we have peformed measurement of urinary ascorbic acid concentration, histopathological examination of the kidney, and biochemical test for the liver function using cadmium-intoxicated rats by oral administration. The average concentrations of urinary ascorbic acid in the $CdCl_2$-treated rats were 214.0 mg/dl for 100 ppm group and 254.3 mg/dl for 200 ppm group during experimental period of 50 days. These levels are 24 and 28 times higher than one in the control group (9.0 mg/dl), respectively. Ultrastructural study showed the eosinophilic hyaline cast and focal effacement, fusion in the renal tubules, as well as loss of foot processes on the glomerular epithelial cells. These results suggested that cadmium may be responsible for renal glomerular injury. The blood levels of AST, ALT and LDH in the treated groups (199 IU/I, 88 IU/I, 1190 U/I for the 100 ppm group and 270 IU/I, 226 IU/I, 760 U/I for the 200 ppm group) were higher than ones in the control group(143 IU/I, 50 IU/I, 334 U/I). These results indicated the cadmium induced the damage of liver function. In conclusion, the administration of cadmium showed a remarkable increase of urinary ascorbic acid with renal and hepatic damage. Therefore, it is expected that measurement of urinary ascorbic acid would be an powerful method as a noninvasive biomarker for cadmium intoxication.

• Korean Journal of Food Science and Technology
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• v.44 no.3
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• pp.324-330
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• 2012

The aim of the present study was to assess the anti-hypercholesterolemic effect of bile salt hydrolase-producing Lactobacillus plantarum CIB 001 (KCTC 11717 bp) in rats fed a high-cholesterol diet. Four treatment groups of rats (n=5) were fed experimental diets: a normal diet (ND), a ND plus L. plantarum CIB 001(NDL) at $5.0-7.5{\times}10^9$ colony forming unit (CFU)/day, a high-cholesterol diet (HCD), as well as a HCD plus L. plantarum CIB 001 (HCDL) at $5.0-7.5{\times}10^9$ CFU/day for 6 weeks. Compared with the HCD group, the HCDL group demonstrated a decrease in serum triglyceride (p<0.05), total cholesterol (p<0.05), and the corresponding HDL-cholesterol concentration increased at a rate of 40% (p<0.05). The HCDL group also induced a decrease in liver inflammation and steatosis. The present results suggest that supplementation of L. plantarum CIB 001 can have short-term (6 weeks) effects on blood lipids and liver injury, as well as on the atherogenic index and cardiac risk factors.

• Journal of Life Science
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• v.23 no.2
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• pp.282-289
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• 2013

This study was conducted to investigate the effect of Makgeolli and Makgeolli precipitate on hepatotoxity and the serum lipid content in rats. First, we investigated the effect of Makgeolli and ethanol on the progress of alcoholic fatty liver. The effect of Makgeolli precipitate on carbon tetrachloride ($CCl_4$)-induced hepatotoxicity in the rats was then studied. Indicators of the health status of the experimental period, the body weight gain in ethanol-treated group tended to be lower than those in the control and the Makgeolli-treated groups. The weight of the liver tissue decreased significantly following the administration of ethanol. However, this was not seen following the administration of Makgeolli. The activities of serum aspartate transaminase (AST) and alanine transaminase (ALT) were decreased in the Makgeolli group compared to the ethanol group. Serum cholesterol concentrations increased in the ethanol group, but decreased in the Makgeolli-treated group to an equal volume of the ethanol-treated group. The serum HDL-cholesterol content was significantly higher in the Makgeolli group than in the ethanol group. Analysis of the impact of the Makgeolli precipitate on toxicity induced by $CCl_4$ in the liver showed that the $CCl_4$ treatment significantly increased the activities of serum ALT and AST. However, the levels of cholesterol and triglyceride in serum were decreased. The $CCl_4$ treatment increased the activities of AST and ALT. However, the raw Makgeolli precipitate decreased their activities. Moreover, raw Makgeolli precipitate significantly reduced the $CCl_4$-induced elevation of serum lipids more than heated Makgeolli precipitate. These results suggest that raw Makgeolli precipitate may exert a protective effect against $CCl_4$-induced liver injury by preventing lipid peroxidation.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.3
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• pp.305-314
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• 2016

Inflammatory and fibrotic responses are accelerated during the reperfusion period, and excessive fibrosis and inflammation contribute to cardiac malfunction. NecroX compounds have been shown to protect the liver and heart from ischemia-reperfusion injury. The aim of this study was to further define the role and mechanism of action of NecroX-5 in regulating inflammation and fibrosis responses in a model of hypoxia/reoxygenation (HR). We utilized HR-treated rat hearts and lipopolysaccharide (LPS)-treated H9C2 culture cells in the presence or absence of NecroX-5 ($10{\mu}mol/L$) treatment as experimental models. Addition of NecroX-5 significantly increased decorin (Dcn) expression levels in HR-treated hearts. In contrast, expression of transforming growth factor beta 1 ($TGF{\beta}1$) and Smad2 phosphorylation (pSmad2) was strongly attenuated in NecroX-5-treated hearts. In addition, significantly increased production of tumor necrosis factor alpha ($TNF{\alpha}$), $TGF{\beta}1$, and pSmad2, and markedly decreased Dcn expression levels, were observed in LPS-stimulated H9C2 cells. Interestingly, NecroX-5 supplementation effectively attenuated the increased expression levels of $TNF{\alpha}$, $TGF{\beta}1$, and pSmad2, as well as the decreased expression of Dcn. Thus, our data demonstrate potential antiinflammatory and anti-fibrotic effects of NecroX-5 against cardiac HR injuries via modulation of the $TNF{\alpha}/Dcn/TGF{\beta}1/Smad2$ pathway.

• Korean Journal of Veterinary Research
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• v.48 no.3
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• pp.337-345
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• 2008

There are accumulating evidences that high levels of dietary iron may play a role in colon carcinogenesis. Elevated iron status has been associated with oxidative stress. Phytic acid (PA) functions as an antioxidant by chelating divalent cations and prevents formation of reactive oxygen species responsible for cell injury and carcinogenesis. The protective effect of PA was investigated on formation of aberrant crypt foci (ACF) induced by azoxymethane (AOM) in iron-overloaded male F344 rats. After acclimation with AIN-93G purified diet (35 ppm Fe, normal control diet) for one week, animals were fed iron-overloaded diet (350 ppm Fe) and PA (0.5% or 2% PA in water) for 8 weeks. Animals received two (1st and 2nd week) injections of AOM (15 mg/kg b.w.) to induce colonic ACF. The colonic mucosa was examined for the total numbers of aberrant crypt (AC) and ACF after staining with methylene blue. The blood and serum were analyzed with a blood cell differential counter and an automatic serum analyzer. Iron-overloaded diet increased the concentration of iron in liver of the rats. But iron-related parameters in blood were not changed among experimental groups. The numbers of ACF per colon and AC per colon were $178.8{\pm}33.2$ and $448.4{\pm}110.2$ in the iron-overloaded F344 rats. The total AC was significantly increased, compared with normal-diet AOM control group (p < 0.05). The treatments of PA at the dose of 0.5% slightly decreased the number of ACF and AC per colon to $153.6{\pm}29.5$ and $396.3{\pm}107.5$. However, there were no significant differences in the total numbers of ACF and AC between the AOM control group and PA (0.5% or 2%)-treated groups. These results suggest that PA may not affect the formation of ACF or AC induced by AOM in ironoverloaded F344 rats.

• Journal of Radiation Protection and Research
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• v.15 no.2
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• pp.27-39
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• 1990

Appreciable radiation exposures certainly were occurred in the reactor burn-up, the nuelear fall-out and the surroundings of nuclear installations with radioactive effluents. Therefore, radioactive nuclides is not only potentially hazardous to workers of nuclear power plants and related industrials, but also the wokers who handle radioactive nuclides in biochemical research and nuclear medicine diagnostics. And in the case of occurring the nuclear accidents, the early medical treatment of radiation injury should be necessary but little is established medical procedures to decontaminate the victims of internal contamination of radioactive nuclides in korea. Accordingly, to achieve the basic data for protective roles and medical treatment of radiation injury, the present studies were carrid out to evaluate the decontamination of uranium by the chemical drugs. The results observed were summarized as follows: 1. The combined treatmet group of sodium bicarbonate and saline with uranyl nitrate injection simultaneously and the dithiothreitol group that was administered 30 minutes after uranyl nitrate injection were increased significantly in the change of body weight than uranyl nitrate-only group (P<0.005). 2. All the experimental groups were increased the fluid intake and urine volume on the uranyl nitrate-induced acute renal failure. but the combined treatment group of sodium bicarbonate and saline with uranyl nitrate injection simultaneously and the dithiothreitol group that was administered 30 minutes after uranyl nitrate injection have the higher increment of fluid intake and urine volume (P<0.05). 3. When sodium bicarbonate and saline was treated with uranyl nitrate injection simultaneously. and dithiothreitol was administered 30 minutes after uranyl nitrate injection. there was significantly reduced in BUN concentration (P<0.01). 4. When dithiothreitol was administered 30 minutes after uranyl nitrate injection. there was reduced more significantly on the increment of serum creatinine concentration than that observed in uranyl nitrate-only group(P<0.01). but when the combined treatment of sodium bicarbonate and saline with uranyl nitrate simultaneously, there was still. albeit much less marked. decrease in serum creatinine concentration. 5. The sodium bicarbonate and saline was treated with uranyl nitrate simultaneously and dithiothreitol was administered at 30 minutes after uranyl nitrate were excreted markedly higher urine creatinine concentration than the uranyl nitrate-only group. 6. Uranyl nitrate has been used in experimental animals to produce hydropic degeneration and swelling of proximal tubules, disappearance of microvilli and brush border or necrosis in the kidney and centrilobular necrosis, congestion, and telangiectasia of the liver. When the sodium bicarbonate and saline was treated with uranyl nitrate simultaneously, and dithiothreitol was administered. 30 minutes after uranyl nitrate, there was more marked the protective effect than uranyl nitrate-only group. Finally, if the sodium bicarbonate and saline may administered as quickly as possible each time that some risk for internal contamination, with uranium, and dithiothreitol is administered 30 minutes after uranium contamination, there ameliorates the course of uranyl nitrate-induced acute renal failure.and this effect is assocciated with prevention of uranium (heavy metal)-induced alterations in BUN, serum creatinine, urine creatinine, fluid intake, urine volume and body weight.