• Toxicological Research
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• v.31 no.1
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• pp.25-32
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• 2015

The objectives of this study were to investigate the individual characteristics, lifestyle habits, exposure levels, and genetic diversity of xenobiotic-metabolizing enzymes involved in toluene metabolism in Korean and foreign workers exposed to toluene at a manufacturing plant. This study was conducted to determine the effects of culture or ethnicity on toluene metabolism. The results showed that blood and urinary toluene concentrations were dependent on the level of exposure to toluene. We analyzed the correlation between toluene metabolism and genetic diversity in glutathione S-transferase (GST) (M1), GSTT1, and cytochrome p-450 (CYP) $2E1^*5$ as well as lifestyle habits (smoking, drinking, and exercise habits). The results revealed significant correlations between toluene metabolism and GSTM1 and GSTT1 genetic diversity, as well as smoking and exercise.

• Asian-Australasian Journal of Animal Sciences
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• v.25 no.6
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• pp.794-799
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• 2012

The cytochrome P450c17-I (CYP17-I) is one of the enzymes critical to gonadal development and the synthesis of androgens. Two single nucleotide polymorphisms (SNPs) were detected within the coding region of the CYP17-I gene in a population of 75 male Japanese flounder (Paralichthys olivaceus). They were SNP1 (c.C445T) located in exon2 and SNP2 (c.T980C (p.Phe307Leu)) located in exon5. Four physiological indices, which were serum testosterone (T), serum $17{\beta}$-estradiol ($E_2$), Hepatosomatic index (HSI), and Gonadosomatic index (GSI), were studied to examine the effect of the two SNPs on the reproductive endocrines of Japanese flounder. Multiple comparisons revealed that CT genotype of SNP1 had a much lower T level than CC genotype (p<0.05) and the GSI of individuals with CC genotype of SNP2 was higher than those with TT genotype (p<0.05). Four diplotypes were constructed based on the two SNPs and the diplotype D3 had a significantly lower T level and GSI. In conclusion, the two SNPs were significantly associated with reproductive traits of Japanese flounder.

• Journal of the Korean Society of Food Science and Nutrition
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• v.40 no.8
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• pp.1099-1106
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• 2011

Cucumber fermentation has been used as a means of preservation. This study was performed to investigate the effects of fermented cucumber beverage (CF) containing beneficial materials for an ethanol hangover based on Hovenia dulcis (SKM) on ethanol-induced hepatotoxicity. Male Sprague-Dawley rats were randomly divided into three groups: ethanol control, ethanol plus SKM, and ethanol plus CF+SKM. SKM or CF+SKM was orally administered at a dose of 7 mL/kg body weight once per day for 5 weeks. Control rats were given an equal amount of water. CF+SKM significantly lowered plasma ethanol levels, whereas SKM tended to decrease the levels compared to the control. Both SKM and CF+SKM significantly lowered the plasma acetaldehyde levels and serum transaminase activities compared to those in the control. SKM and CF+SKM did not affect hepatic alcohol dehydrogenase activity; however, it significantly inhibited cytochrome P450 2E1 (CYP2E1) activity. Hepatic aldehyde dehydrogenase (ALDH) activity was significantly higher in the SKM and CF+SKM groups than that in the control group. Plasma acetaldehyde concentration was significantly correlated with hepatic CYP2E1 (r=0.566, p<0.01) activity and ALDH (r=-0.564, p<0.01) activity. Hepatic superoxide dismutase and catalase activities as well as glutathione content increased with the SKM and CF+SKM administration, whereas lipid peroxide content decreased significantly. Furthermore, SKM and CF+SKM lowered plasma and hepatic lipid content and lipid droplets compared to those in the control group. These results indicate that SKM and CF+SKM exhibit hepatoprotective properties partly by inhibiting CYP2E1 activity, enhancing ALDH activity and stimulating the antioxidant defense systems in ethanol-treated rats.

• Preventive Nutrition and Food Science
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• v.13 no.4
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• pp.269-275
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• 2008

Dandelion (Taraxacum officinale) has been widely used as an anti-inflammatory agent in oriental medicine. In the current study, we investigated the protective effect, and the possible mechanism, of dandelion extracts against ethanol-induced acute hepatotoxicity in C57BL/6 mice. Dandelion water and ethanol extract was administered at 2 g/kg body weight (BW) once daily for 7 consecutive days, whereas control and ethanol groups received water by gavage. Ethanol (50% ethanol; 6 g/kg BW) was administered 12 hr before sacrificing the mice in order to generate liver injury. Significantly increased serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities as well as liver triglyceride (TG) and cholesterol levels were attenuated by dandelion supplementation. In addition, dandelion extracts not only enhanced alcohol dehydrogenase (ADH) and anti-oxidative enzyme activities, but reduced lipid peroxidation. Cytochrome P450 2E1 (CYP 2E1), one of the critical enzymes xenobiotic metabolism, expression was lower with ethanol treatment but restored by dandelion supplementation. These results were confirmed by improved histopathological changes in fatty liver and hepatic lesions induced by ethanol. In conclusion, dandelion could protect liver against ethanol administration by attenuating of oxidative stress and inflammatory responses.

• The Korean Journal of Pharmacology
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• v.32 no.1
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• pp.75-82
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• 1996

The hypothesis that calcium provoke $O_2^-$ formation by Kupffer cells and may contribute to carbon tetrachloride $(CCl_4)$ induced liver injury was studied in SD rats. In $CCl_4-treated$ animals, hepatic malonaldehyde (nmole/gm liver) and plasma ALT (IU/ml) levels elevated significantly from $119.63{\pm}13.00$ to $268.97{\pm}14.82$ and from $17.3{\pm}0.18$ to $806.08{\pm}37.63$, respectively, compared to those in controls. Activation of Kupffer cells with high dose of retinol (250,000 IU/kg/day, po, for 7 day) significantly enhanced ALT levels, while inactivation of Kupffer cells with gadolinium chloride (7.5 mg/kg/day, ip, for 2 day) attenuated the increase of serum ALT level following $CCl_4$ treatment. Diltiazem (10 mg/kg/day, ip for 2 day) given in combination with retinol led to a marked decrease in ALT levels compare to the level in rats treated only with retinol against $CCl_4$ treatment. In order to determine any alterations in cytochrome P450 activities, the P450 content and the CYP2E1 activity were measured and all $CCl_4-treated$ rats showed significantly lower levels compared to those in controls and vehicle-treated animals. There were significant increases in glutathione peroxidase in all $CCl_4-treated$ rats except diltiazem treated groups. No difference was found among untreated and vehicle-treated rats. It is concluded that Kupffer cells contribute to $CCl_4-induced$ liver injury and that calcium antagonist attenuated the increased $CCl_4-induced$ liver injury due to activation of Kupffer cells.

• Food Science of Animal Resources
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• v.42 no.6
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• pp.1046-1060
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• 2022

This study aimed to investigate the effects of the metabolites of Latilactobacillus curvatus BYB3 and indole-activated aryl hydrocarbon receptor (AhR) to increase the tight junction (TJ) proteins in an in vitro model of intestinal inflammation. In a Western blot assay, the metabolites of L. curvatus BYB3 reduced the TJ demage in lipoploysaccharide (LPS) stimulated-Caco-2 cells. This reduction was a result of upregulating the expression of TJ-associated proteins and suppressing the nuclear factor-κB signaling. Immunofluorescence images consistently revealed that LPS disrupted and reduced the expression of TJ proteins, while the metabolites of L. curvatus BYB3 and indole reversed these alterations. The protective effects of L. curvatus BYB3 were observed on the intestinal barrier function when measuring transepithelial electrical resistance. Using high-performance liquid chromatography analysis the metabolites, the indole-3-latic acid and indole-3-acetamide concentrations were found to be 1.73±0.27 mg/L and 0.51±0.39 mg/L, respectively. These findings indicate that the metabolites of L. curvatus BYB3 have increasing mRNA expressions of cytochrome P450 1A1 (CYP1A1) and AhR, and may thus be applicable for therapy of various inflammatory gut diseases as postbiotics.

• YAKHAK HOEJI
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• v.54 no.6
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• pp.522-528
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• 2010

This study was designed to examine the effect of estrogen deficiency on the metabolism of ethanol in ovariectomized rats. Female rats were assigned to an ovariectomy (OVX) and a sham (SHAM) surgery group. Gain body weight was greater in incresed in OVX group and especially uterus weight significantly decrease depending on the concentration of estrogen after 3 month of ovariectomy. Ethanol at the tolerative dose (6 g/kg) was injected to rats by oral administration to measure the concentration of ethanol in blood. The area under the blood concentration time curve (AUC) was significantly lower in OVX group than SHAM group. The significant decrease in AUC in OVX group indicates that the estrogen deficiency leads to changes of the factors related to ethanol metabolism. Activity of hepatic alcohol dehydrogenase was not significantly influenced by the ovariectomy and also the ethanol elimination rate in vivo was not different. Cytochrome P450 isozymes did not show any changes except CYP 1A1 and 2E1. Level of hepatic glutathione in OVX group was higher after treatment of ethanol. Therefore the reduction of AUC appears not to be directly associated with the difference of ethanol metabolizing enzyme, but to be related with the physical factors like body weight.

• Korean Journal of Veterinary Research
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• v.60 no.4
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• pp.215-223
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• 2020

Sasa (S.) quelpaertensis Nakai (Korean name, Jeju-Joritdae), which has anti-oxidative and anti-inflammatory activities, is a type of bamboo grass distributed widely in Jeju Island, Korea. S. quelpaertensis leaves are used for therapeutic purposes in traditional Korean medicine. This study examined the hepatoprotective effects of the S. quelpaertensis ethyl acetate fraction (SQEA) in a mouse model to mimic alcoholic liver damage. The mice were administered orally with 30% alcohol (5 g/kg) once per day with or without SQEA treatments (100 and 200 mg/kg) for 14 days consecutively. Alcohol consumption increased the serum alcohol content and histopathological changes but reduced the liver weight. Moreover, the livers of the alcohol group exhibited the accumulation of malondialdehyde and cytochrome P450 2E1 (CYP2E1), and lipid droplet coating protein perilipin-2. On the other hand, SQEA dose-dependently attenuated the alcohol-induced serum ethanol content and liver histopathological changes but increased the liver weight. Moreover, SQEA attenuated the level of CYP2E1 and inhibited alcohol-induced lipogenesis in the liver via decreased perilipin-2 expression. These results suggest that SQEA can provide a potent way to reduce the liver damage caused by alcohol consumption.

• Environmental Analysis Health and Toxicology
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• v.31
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• pp.10.1-10.8
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• 2016

Objectives Aromatase inhibitors that block estrogen synthesis are a proven first-line hormonal therapy for postmenopausal breast cancer. Although it is known that standardized extract of Ginkgo biloba (EGb761) induces anti-carcinogenic effects like the aromatase inhibitors, the effects of EGb761 on steroidogenesis have not been studied yet. Therefore, the effects of EGb761 on steroidogenesis and aromatase activity was studied using a H295R cell model, which was a good in vitro model to predict effects on human adrenal steroidogenesis. Methods Cortisol, aldosterone, testosterone, and $17{\beta}$-estradiol were evaluated in the H295R cells by competitive enzyme-linked immunospecific assay after exposure to EGb761. Real-time polymerase chain reaction were performed to evaluate effects on critical genes in steroid hormone production, specifically cytochrome P450 (CYP11/ 17/19/21) and the hydroxysteroid dehydrogenases ($3{\beta}$-HSD2 and $17{\beta}$-HSD1/4). Finally, aromatase activities were measured with a tritiated water-release assay and by western blotting analysis. Results H295R cells exposed to EGb761 (10 and $100{\mu}g/mL$) showed a significant decrease in $17{\beta}$-estradiol and testosterone, but no change in aldosterone or cortisol. Genes (CYP19 and $17{\beta}$-HSD1) related to the estrogen steroidogenesis were significantly decreased by EGb761. EGb761 treatment of H295R cells resulted in a significant decrease of aromatase activity as measured by the direct and indirect assays. The coding sequence/Exon PII of CYP19 gene transcript and protein level of CYP19 were significantly decreased by EGb761. Conclusions These results suggest that EGb761 could regulate steroidogenesis-related genes such as CYP19 and $17{\beta}$-HSD1, and lead to a decrease in $17{\beta}$-estradiol and testosterone. The present study provides good information on potential therapeutic effects of EGb761 on estrogen dependent breast cancer.

• Journal of Periodontal and Implant Science
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• v.53 no.1
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• pp.20-37
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• 2023

Purpose: Our pilot study showed that a 3-dimensional dual drug delivery scaffold (DDDS) loaded with Chinese herbs significantly increased the regenerated bone volume fraction. This study aimed to confirm the synergistic anti-inflammatory and osteogenic preclinical effects of this system. Methods: The targets and pathways of parthenolide and naringin were predicted. Three cell models were used to assess the anti-inflammatory effects of parthenolide and the osteogenic effects of naringin. First, the distance between the cementoenamel junction and alveolar bone crest (CEJ-ABC) and the bone mineral density (BMD) of surgical defects were measured in a rat model of periodontitis with periodontal fenestration defects. Additionally, the mRNA expression levels of matrix metallopeptidase 9 (MMP9) and alkaline phosphatase (ALP) were measured. Furthermore, the number of inflammatory cells and osteoclasts, as well as the protein expression levels of tumor necrosis factor-alpha (TNF-α) and levels of ALP were determined. Results: Target prediction suggested prostaglandin peroxidase synthase (PTGS2) as a potential target of parthenolide, while cytochrome P450 family 19 subfamily A1 (CYP19A1) and taste 2 receptor member 31 (TAS2R31) were potential targets of naringin. Parthenolide mainly targeted inflammation-related pathways, while naringin participated in steroid hormone synthesis and taste transduction. In vitro experiments revealed significant antiinflammatory effects of parthenolide on RAW264.7 cells, and significant osteogenic effects of naringin on bone marrow mesenchymal stem cells and MC3T3-E1 cells. DDDS loaded with parthenolide and naringin decreased the CEJ-ABC distance and increased BMD and ALP levels in a time-dependent manner. Inflammation was significantly alleviated after 14 days of DDDS treatment. Additionally, after 56 days, the DDDS group exhibited the highest BMD and ALP levels. Conclusions: DDDS loaded with parthenolide and naringin in a rat model achieved significant synergistic anti-inflammatory and osteogenic effects, providing powerful preclinical evidence.