• Nutrition Research and Practice
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• v.10 no.6
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• pp.623-628
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• 2016

BACKGROUND/OBJECTIVES: Obesity-induced steatohepatitis accompanied by activated hepatic macrophages/Kupffer cells facilitates the progression of hepatic fibrinogenesis and exacerbates metabolic derangements such as insulin resistance. Heme oxyganase-1 (HO-1) modulates tissue macrophage phenotypes and thus is implicated in protection against inflammatory diseases. Here, we show that the flavonoid quercetin reduces obesity-induced hepatic inflammation by inducing HO-1, which promotes hepatic macrophage polarization in favor of the M2 phenotype. MATERIALS/METHODS: Male C57BL/6 mice were fed a regular diet (RD), high-fat diet (HFD), or HFD supplemented with quercetin (HF+Que, 0.5g/kg diet) for nine weeks. Inflammatory cytokines and macrophage markers were measured by ELISA and RT-PCR, respectively. HO-1 protein was measured by Western blotting. RESULTS: Quercetin supplementation decreased levels of inflammatory cytokines ($TNF{\alpha}$, IL-6) and increased that of the anti-inflammatory cytokine (IL-10) in the livers of HFD-fed mice. This was accompanied by upregulation of M2 macrophage marker genes (Arg-1, Mrc1) and downregulation of M1 macrophage marker genes ($TNF{\alpha}$, NOS2). In co-cultures of lipid-laden hepatocytes and macrophages, treatment with quercetin induced HO-1 in the macrophages, markedly suppressed expression of M1 macrophage marker genes, and reduced release of MCP-1. Moreover, these effects of quercetin were blunted by an HO-1 inhibitor and deficiency of nuclear factor E2-related factor 2 (Nrf2) in macrophages. CONCLUSIONS: Quercetin reduces obesity-induced hepatic inflammation by promoting macrophage phenotype switching. The beneficial effect of quercetin is associated with Nrf2-mediated HO-1 induction. Quercetin may be a useful dietary factor for protecting against obesity-induced steatohepatitis.

• Korean Journal of Microbiology
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• v.23 no.4
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• pp.291-296
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• 1985

Leptospira isolated from patients and natural paddy water were further studied to confirm their serologic specificity with the bacteria in infected animal tissue and autopsied tissue of patients died with leptospirosis. And pathologic patterns of the inoculated antimal and the virulence of the bacteria in the animals were also studied. The findings are summarized as follows; $LD_{50}$ dose of the bacteria in guinea-pig were $1-2{\times}10^9$ cells and mice were found to be susceptible to them even though the degree of susceptibilities were much inferior to guinea pig. The bacteria were recovered from various organs; demonstrated massive hemorrages due to diapedesis and monocyte infiltration were observed, in some cases, intramedullary hemorrages of the infected kidnies and hematuria were recognized. All of the hyperimmune sera were strongly reacted with the tissues from autopsied human case who died of EPHF(Epidemic Pulmonary Hemorrhagic Fever) in immunofluorescent antibody tests.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.3
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• pp.642-646
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• 2007

It was examined that the effect of fermented traditional wine made by using mycelium of Phellinus linteus (TWPL) on the expression of inflammation-related proteins in rat liver. Levels of aspartate aminotransferase (AST) was significantly increased in the serum of ethanol-treated rats compared to normal. However, the level of AST showed no significant changes in the TWPL-treated rat compared normal. Slight histopathological changes of liver such as cloudy swelling, inflammatory cells infiltration, Kupffer cell reaction were demonstrated in the rats challenged with ethanol compared with normal. Fewer scores of these changes were observed in TWPL-treated rat with recovered glycogen in hepatocytes of whole hepatic lobule. The RT-PCR and Western analysis showed that the expression of inflammatory proteins such as cyclooxygenase-2, inducible nitric oxide synthase, tumor necrosis factor (TNF)-${\alpha}$ were decreased in the TWPL-treated rat compared with ethanol-treated ones. Immunohistochemical analysis showed that the expression of interleukin-lf and TNF-${\alpha}$ tended to decrease in TWPL-treated rat compared with ethanol-treated ones. These results suggest that TWPL may contains some protective agent for alcohol-induced liver injury through a regulating inflammation-related proteins.

• Animal Bioscience
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• v.36 no.1
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• pp.98-107
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• 2023

Objective: Current quail production is configured as an economic activity in scale. Advancements in quail nutrition have been limited to areas such as breeding and, automation of facilities and ambience. The objective of this study was to evaluate the performance responses, liver and oviduct morphometry, and liver histology of Japanese laying quails subjected to different levels of nitrogen-corrected apparent metabolizable energy (MEn). Methods: A completely random design was used that consisted of nine levels of MEn, six replicates, and five hens per cage with a total of 270 quails. The experimental period lasted for 10 weeks. The variables of performance were subjected to analysis of variance and then regression analysis using the broken-line model. The morphometric and histological variables were subjected to multivariate exploratory techniques. Results: The MEn levels influenced the responses to zootechnical performance. The broken-line model estimated the maximum responses for feed intake, egg production, egg weight, and egg mass as 3,040, 2,820, 1,802, and 2,960 kcal of MEn per kg of diet, respectively. Multivariate analysis revealed that the occurrence of hepatic steatosis and increased levels of Kupffer cells were not related to MEn levels. Conclusion: The level of 2,960 kcal/kg of MEn meets performance variable requirements without compromising hepatic physiology.

• Korean Journal of Veterinary Research
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• v.57 no.4
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• pp.215-222
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• 2017

Temporal and subcellular distributions of hyaluronic acid (HA) as a degradable nanoparticle (NP) in animals were investigated to determine if HA-NP could be utilized as an appropriate drug delivery system. After mice were intravenously injected with 5 mg/kg of Cy5.5-labeled HA-NP sized 350-400 nm or larger HA-polymers, the fluorescence intensity was measured in all homogenized organs from 0.5 h to 28 days. HA-NP was greatly detected in spleen, liver and kidney until day 28, while it was maintained at low levels in other organs. HA-polymer was observed at low levels in all organs. HA-NP quantities in spleen and liver were reduced until day 3, but increased sharply between days 3 and 7, then decreased again, while their HA-polymers were maintained at low levels until day 28. In kidneys, both HA-NP and HA-polymer showed high levels after 0.5 h of administration, but steadily decreased until day 28. According to ultrastructural analyses, HA-NP was engulfed in Kupffer cells of liver and macrophages of spleen and kidney at day 1 and was accumulated in the cytoplasm of kidney tubular cells at day 7. Overall, these findings suggest that HA-NP could be considered a desirable drug carrier in the liver, kidney, or spleen.

• Asian-Australasian Journal of Animal Sciences
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• v.24 no.10
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• pp.1425-1434
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• 2011

This experiment was designed to evaluate the effects of the processing method of common vetch seed (CVS) (Vicia sativa) on laying performance, egg quality, metabolic parameters and liver histopatology during the peak production period in hens. Lohman layers, 46 wk of age in 6 replicate cages each containing 4 hens, were allocated randomly to one of four dietary treatments. Diets were control (C) diet containing no common vetch and experimental diets containing 25% raw common vetch (RCV), 25% soaked in water for 72 h with exchange of water every 24 h (SCV) and 25% soaked&boiled at $100^{\circ}C$ for 30 minute common vetch (SBCV). Inclusion of RCV into the diet deteriorated all laying performance variables. SCV did not alleviate the adverse effect of raw common vetch on feed intake, egg weight, feed conversion, final weight and weight change. SCV partially alleviated egg production (p<0.001). SBCV diminished the adverse effect on feed intake, egg weight, feed conversion, final weight and weight change compared to raw vicia sativa (p<0.001). No significant difference was detected between SBCV and the control group in terms of egg production, feed conversion, final weight and weight change. Regardless of the processing method, all the common vetch groups had lower shell strength compared to the control group. Haugh units did differ between all groups (p<0.001). Inclusion of RCV and SCV into the basal diet decreased triglyceride, cholesterol, total protein and serum glucose concentrations (p<0.001). Hovewer, inclusion of SBCV into the basal diet increased these parameters. Liver samples were stained with Hematoxylin and eosin (HE) and evaluated by light microscopy. A biopsy of native liver tissue was used as a control. No histopathologic finding was present in the control group. Raw V. sativa compared with the control caused lipid accumulations in hepatocytes, severe congestion of hepatic blood vessels, inflammation, increased numbers of Kupffer cells and sinusoidal dilatations. Whereas, the livers from groups given treated V. sativa showed only different degrees of sinusoidal dilatations. Findings from the present study point out the risk of increased hepatic damage due to use of raw Vicia sativa. Increasing treatment of V. sativa lead to a decrease of liver damages. Inclusion of raw and soaked vetch seeds in rations affected adversely all parameters examined in laying hens. But alleviation was observed when soaked and boiled vetch seeds (SBCV) were fed. The results of these experiments indicated that soaked&boiled Vicia sativa seeds may safely be used at a 25% level in rations of laying hens.

• Applied Microscopy
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• v.31 no.1
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• pp.37-47
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• 2001

In order to investigate a pathogenesis of liver damage induced by skin burn, thermal injury was induced by scald burn on entirely dorsal surface in rats (total burn surface area $20\sim25\%$) except for inhalated injury. At 5 and 24 h after scald burn, biochemical assay and morphological changes in serum and liver tissue were examined. Skin burn increased liver weight (% of body weight, p<0.05) and the activity of serum aniline amino-transferase (ALT, p<0.05), in addition, the activity of xanthine oxidase (XO), an enzyme of oxygen free radical generating system, was elevated (p<0.01) in serum, but not in skin and in liver. Postburn treatment of allopurinol intraperitoneally decreased liver weight, serum ALT activity and serum XO activity. Scald burn induced ultrastructurally swelling of endoplasmic reticulum, ribosome detachment, accumulation of lipid, dilatation of bile canaliculi and intercellular space, neutrophil infiltration, activation of Kupffer's cells and degeneration of hepatocytic microvilli. Futhermore , thermal injury decreased not only the protein concentration in plasma but also the number of intravascular leukocytes, that indicates induction of edema formation with protein exudation and inflammation by neutrophil infiltration into the internal organs. However allopurinol injection after burn inhibited post burn ultrastructural changes. These data suggest that acute dermal scald burn injury leads to liver damage, that is related to elevation of xanthine oxidase activity in serum. Xanthine oxidase may be a key role in the pathogenesis of liver damage induced by skin burn.

• Journal of Life Science
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• v.14 no.2
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• pp.215-220
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• 2004

We investigated the anti-inflammatory effects of aqueous extract of Artemisia capillaris Thunb. (AEAC), a traditional Korean herb for remedying liver disease, for suppression in the process of lipopolysaccharide (LPS)-induced inflammation in the liver of rat. Level of glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT) and lactate dehydrogenase (LDH) was increased in the serum of LPS-treated rats compared to normal, however, in the rats pretreated with AEAC, the increase of GOT, GPT and LDH value was arrested. More severe histological changes of liver such as cloudy swelling, hydropic degeneration, Kupffer cell reaction and inflammatory cells infiltration were demonstrated in the rats challenged with LPS compared with normal. Fewer scores of these changes were observed in rats pretreated with AEAC. Immunohistochemical analysis showed that while the expression of the nuclear factor (NF)-kBp65, inducible nitric oxide synthase (iNOS), tumor necrosis factor (TNF)-$\alpha$ and COX (cyclooxygenase)-2 tended to increase, that of inhibitory (I)-kBa was decreased in the hepatocytes of rats challenged with LPS. A slight decline of NF-kBp65, TNF-$\alpha$ and COX-2, but increase of I-kB$\alpha$ were observed in the hepatocytes of the rats pretreated with AEAC. These results suggest that AEAC may act as a therapeutic agent for liver disease through a regulation of inflammation-related proteins.

• Journal of Life Science
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• v.16 no.6
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• pp.978-983
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• 2006

We investigated the anti-inflammatory effects of mycelial culture extract from Phellinus linteus (MCPL) for suppression in the process of ethanol-induced inflammation in rat liver. Levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were significantly increased in the serum of ethanol-treated rats compared to normal. However, the level of ALT was arrested markedly in ethanol-treated rats with MCPL compared to ethanol alone treated control ones. Severe histopathological changes of liver such as cloudy swelling, inflammatory cells infiltration, Kupffer cell reaction and focal necrosis were demonstrated in the rats challenged with ethanol compared with normal. Fewer scores of these changes were observed in MCPL-treated rat with recovered glycogen in centrolobular region of hepatic lobule. The Western analysis showed that the expression of inflammatory proteins such as cyclooxygenase (COX)-1, COX-2, inducible nitric oxide synthase (iNOS), tumor necrosis factor $(TNF)-{\alpha}$ were increased in the ethanol-treated rat. But decline of COX-2 and iNOS expression were observed in MCPL-treated rat. Immunohistochemical analysis showed that the expression of COX-2 and $TNF-{\alpha}$ tended to increase in ethanol-treated rat, but decrease of these reactions were induced by MCPL treatment. These results suggest that MCPL may act as a protective agent for alcohol-induced liver injury through a regulating inflammation-related proteins.

• Korean Journal of Animal Reproduction
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• v.23 no.1
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• pp.1-12
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• 1999

The present study was conducted to find the effects of different cadmium(Cd) levels in diets on clinical toxicity, sperm capacity and histopathological changes in rats. Thirty male rats of Sprague-Dawley weighing 125.3$\pm$15.2g were randomly blocked into five groups according to body weights. Five levels of Cd in AIN-76 purified diet(0, 25, 50, 100 and 250 ppm) had been fed for 8 weeks. Cadmium was supplemented with a form of CdCl$_2$. 1. After 8 weeks of Cd intake had resulted in apparent cadmium intoxication; reduced growth rate, enlarged kidney and testis, decreased hematocrit value and hemoglobin content in response to supplemented Cd levels in the diets. 2. Cadmium accumulation in liver and kidney showed a tendency to increase in cadmium-exposed groups. The levels of metallothionein were also significantly elevated in the tissues of liver in response to the levels of Cd supplemented(P＜0.05). 3. Although sperm motility was not significantly different among treatments, rats fed Cd tended to have reduced sperm motility but sperm concentration of Cd supplemented groups were significantly lower than that of control(p＜0.05). 4. Based on the findings from gross lesion, rats fed 250ppm of Cd were externally emaciated, had exposed penis and observed atrophies of kidney and testis. Histopathological observation seemed that the liver of groups feeding Cd supplemented diets showed cellular degeneration and accumulation of eosinophilic materials in the capillaries. In kidney, rats fed Cd diets had shown tubular epithelium degeneration and lesions of basophilic materials, while testes were weakened in numbers of spermatid and sporadically enlarged of giant cells.