• Journal of Veterinary Science
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• v.22 no.3
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• pp.36.1-36.12
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• 2021

Background: Mouse hepatitis virus (MHV) A59 is a highly infectious pathogen and starts in the respiratory tract and progresses to systemic infection in laboratory mice. The complement system is an important part of the host immune response to viral infection. It is not clear the role of the classical complement pathway in MHV infection. Objectives: The purpose of this study was to determine the importance of the classical pathway in coronavirus pathogenesis by comparing C1qa KO mice and wild-type mice. Methods: We generated a C1qa KO mouse using CRISPR/Cas9 technology and compared the susceptibility to MHV A59 infection between C1qa KO and wild-type mice. Histopathological and immunohistochemical changes, viral loads, and chemokine expressions in both mice were measured. Results: MHV A59-infected C1qa KO mice showed severe histopathological changes, such as hepatocellular necrosis and interstitial pneumonia, compared to MHV A59-infected wild-type mice. Virus copy numbers in the olfactory bulb, liver, and lungs of C1qa KO mice were significantly higher than those of wild-type mice. The increase in viral copy numbers in C1qa KO mice was consistent with the histopathologic changes in organs. These results indicate that C1qa deficiency enhances susceptibility to MHV A59 systemic infection in mice. In addition, this enhanced susceptibility effect is associated with dramatic elevations in spleen IFN-γ, MIP-1 α, and MCP-1 in C1qa KO mice. Conclusions: These data suggest that C1qa deficiency enhances susceptibility to MHV A59 systemic infection, and activation of the classical complement pathway may be important for protecting the host against MHV A59 infection.

• Toxicological Research
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• v.35 no.2
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• pp.131-136
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• 2019

Ethylhexyl dimethyl para-aminobenzoic acid (PABA) is an oily yellow liquid derivative of water-soluble PABA commonly used in sunscreen. Ethylhexyl dimethyl PABA is widely used as an ingredient in many cosmetics at an average concentration of 1.25% (0.5-2.0%) in Korea. Previous studies, including those involving animals, have demonstrated that ethylhexyl dimethyl PABA is toxic to the following four organs: testis, epididymis, spleen, and liver. In addition, experiments using human keratinocytes found that ethylhexyl dimethyl PABA inhibits cell growth and DNA synthesis at low concentrations, and halted the cell cycle of MM96L cells (human melanoma cell line) at the G1 phase. Despite limited clinical data in humans, many studies have confirmed increased mutagenicity of ethylhexyl dimethyl PABA following exposure to sunlight, which suggests that this molecule is likely to contribute to onset of sun-induced cancer despite protecting the skin through absorption of UVB. For risk assessment, the no observed adverse effect level (NOAEL) chosen was 100 mg/kg bw/day in a 4 weeks oral toxicity study. Systemic exposure dosage (SED) was 0.588 mg/kg bw/day for maximum use of ethylhexyl dimethyl PABA in cosmetics. Based on the risk assessment and exposure scenarios conducted in this study, the margin of safety (MOS) was calculated to be 180.18 for a sunscreen containing 8% ethylhexyl dimethyl PABA, which is the maximum level allowed by the relevant domestic authorities.

• Korean Journal of Food Science and Technology
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• v.49 no.6
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• pp.676-684
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• 2017

The present study aimed to examine the hepatoprotective effects of ethanol extracts from steam-dried ginseng berry (SGBE) in both $\text\tiny{D}$-Galactosamine/Lipopolysaccharide ($\text\tiny{D}$-GalN/LPS)-sensitized mice and in vitro models. Our results clearly demonstrated that SGBE significantly reduced the level of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and lactate dehydrogenase in blood, and $TNF{\alpha}$ was normalized in 8 h after the treatment with $\text\tiny{D}$-GalN/LPS. Coincidently, major organs remained unimpaired when compared to $\text\tiny{D}$-GalN/LPS control group. Moreover, p38, which stimulates expression of NAFLD-associated cytokines, was markedly inhibited when treated with SGBE. In vitro analysis revealed that the main components of SGBE, linoleic acid and ginsenoside Re/Rd, may play a role in protecting liver from $\text\tiny{D}$-GalN/LPS-induced toxicity. Finally, we concluded that SGBE may be a promising therapeutic agent for preventing damage to the liver.

• Korean Journal of Medicinal Crop Science
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• v.7 no.2
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• pp.107-114
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• 1999

It has long been recognized that dropwort contains specific funtional subtances for protecting human liver and preventing and curing its diseases, and thus it has been widely utilized in traditional folk remedy. In the present study. fresh of fermented extract of dropwort shoots grown on dryland and fresh extract of those grown on flooded fie1d were fed to the rats suffering from acute, subacute or chronical toxication induced by alcohol administration, and their affects were investigated. Administration of alcohol to rats and mice for 2 days at 5ml of 30% EtOH/kg/day raised total cholesterol and total glyceride which were, however, great1y supressed when alcohol was administered to the laboratory animals previously fed on fresh or fermented extract of dryland dropwort, or fresh extract of flooded field-grown dropwort for 20 days, without significant differences among the extracts. The levels of alanine aminotransferase and aspartate aminotransferase which were raised by alcohol adminstration were also lowered by feeding dropwort extract, among which that of fermented dryland-grown one was more effective than the other two. Chronic alcohol toxication was induced to rats by administering 10% alcohol for 10 months and fermented dropwort extract or tap water was fed to the rats for 5 days. The rats fed on fermented dropwort extract were lower in total cholesterol by 40% and in tota1 glyceride by 60% than the control. Alanine aminotransferase and aspartate aminotransferase in the rats fed on fermented dropwort extract were decreased by 87.2% and 91.7%, respectively, compared to the control, and the rats recovered almost to normal. Activity of alkaline phosphatase, catalase, superoxide dismutase or glutathione peroxidase changed greatly by alcohol administration in the rats suffering from chronic as well as acute toxication. The extract of fermented dry land dropwort significantly lowed the activity of those enzymes, especially, alkaline phosphatase and superoxide dismutase. The present results suggesting the possible medicinal effect of fermented dropwort extract to liver diseases.

• The Journal of Internal Korean Medicine
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• v.29 no.4
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• pp.1000-1010
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• 2008

Objective : Hypothyroidism is a syndrome characterized by symptoms such as cold intolerance, or weight gain. Because of side effects of Western medicine treatment, interest in oriental medicine has been increasing. In this study, we examined the therapeutic effects of Evodiae fructus and histological modification in hypothyroidism rat model induced by PTU(6-propyl, 2-thiouracil). Methods : After inducing hypothyroidism in the rats by PTU injections, we divided the rats into four groups, the Evodiae fructus 100 500, control, and $LT_4$ (levothyroxine) groups. After 2 weeks Evodiae fructus and $LT_4$ were administered, respectively. The weight was measured once a week. After sampling the blood for biochemical analysis to check the levels of $T_3$, $T_4$ and TSH, the thyroid tissue was removed, stained with H&E, and an image was obtained using an optical microscope. Results : Compared with normals, controls showed low $T_4$ and high TSH. The Evodiae fructus group showed a statistically meaningful $T_3$ increase to be dose related. But the levels of TSH showed no meaningful difference between the Evodiae fructus group and normals. About the biochemical tests(liver, kidney etc) and weight change, there was no meaningful difference between the Evodiae fructus group and controls. In the biopsy, the Evodiae fructus group showed thyroid tissue improvement compared to controls. Conclusions : These results show that Evodiae fructus stimulates the decreased functions of the thyroid, and also has thyroid cell protecting effects. The lab results also showed that Evodiae fructus is a safe substance that doesn't cause hepatotoxicity or nephrotoxicity. Therefore it is an effective substance in the treatment of hypothyroidism.

• Korean Journal of Food Science and Technology
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• v.41 no.6
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• pp.706-711
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• 2009

Hepatoprotective effects of corn gluten hydrolysates (CGH) were investigated in rats orally treated with ethanol (30%(v/v), 3 g/kg body weight/day) for 4 weeks. Six-week old Sprague-Dawley male rats were divided into four dietary groups: normal diet (N), alcohol diet (E), E+CGH 1% diet (CGH-1%), and E+CGH 3% diet (CGH-3%). Body weights and liver indices were not significantly different among the four groups. However, food intakes were lower in the CGH groups than in the normal group (p<0.05). The administration of CGH significantly reduced serum alkaline phosphatase activity by 30% compared to the alcohol diet group. Among the antioxidative enzymes assessed, catalase activity was significantly decreased by 79% in the CGH diet groups compared to the alcohol diet group. In comparison to the alcohol-treated group, aldehyde dehydrogenase activity was increased by 20%, while microsomal ethanol oxidizing system activity was decreased by 20% in the CGH-treated groups. Furthermore, the area under the curve of the blood acetaldehyde concentration versus time profile after the administration of ethanol was significantly lower for the CGH rats than for the ethanol or asparaginic acid treated groups. Thus, CGH seems to offer beneficial effects by protecting against ethanol-induced hepatotoxicity by improving the acetaldehyde-related metabolizing system.

• Journal of Nutrition and Health
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• v.25 no.6
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• pp.476-484
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• 1992

The influence of selenuium deficiency and fish oil on lipid peoxidation status and fatty acid composition of tissues(plasma aorta and liver) was studied. Male Sprague Dawley rats were fed for eight weeks semipurified diets containing 7% corn oil(by weight) or 5, 5% fish oil(MaxEPA) plus 1.5% corn oil with oil with or without selenium status (glutathione peroxidase activity and selenium levels) were significantly lower in the rats given inadequate selenium in plasma aorta (p<0.02 and p<0.001 respectively) gut not that in plasma Selenium supplementation decreased hepatic MDA levels(p<0.02) Increases in the levels of 20:5(n-3) 22:5(n-3), 22:6(n-3) 20:3(n-6) and a decrease in the level of 20:4(n-6) were observed in plasma total lipids and aortic and hepatic phospholipids when fish oil was fed. Though selenium supplementation increased the level of n-3 fatty acids(such as 22:6(n-3)) in plsama and the aorta is overall effect was smaller than the effect of fish oil feeding. These data suggest that selenium may play a significant but minor role in protecting against lipid peroxide-tion even when vitamin E intakes are in excess of current recommendations in both corn oil and fish oil diets.

• The Journal of Korean Medicine
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• v.27 no.3 s.67
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• pp.107-131
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• 2006

Background and Aims: Dansamtongmek-tang (DSTMT) and Dansamsengmek-san (DSSMS) have been used for many years as therapeutic agents for the acute stage of cerebrovascular disease, hypertension and hyperlipidemia in Oriental medicine, but the effects of DSTMT and DSSMS on hyperlipidemia and safety for cell damage are not yet well-known. This study was done to investigate the effects of DSTMT and DSSMS on hyperlipidemia. Methods: In vivo test: after administering DSTMT and DSSMS to SHR and ICR occurred hyperlipidemia for 3 weeks, we analyzed body weight, cholesterol levels. TG, HDL-chol, LDL-chol, LDH in plasma, brain, liver and kidney tissue, and DNA by RT-PCR. In vitro test: after administering DSTMT and DSSMS to human hepatocellular carcinoma in hypoxia, we observed cell cohesion by light microscope, analyzed the inflow of Ca2+ by confocal laser scanning microscope and DNA by RT-PCR. Results: DSTMT significantly decreased the levels of triglyceride and increased the levels of HDL-cholesterol in SHR, and significantly decreased the levels of LDL-cholesterol and body weight and increased the levels of HDL-cholesterol in ICR. DSSMS significantly decreased body weight, total cholesterol levels, LDL-cholesterol, LDH and cardiac risk factor (CRE) in SHR and significantly decreased the levels of total cholesterol, triglyceride, LDL-cholesterol, LDH and CRF in ICR. DSTMT had an effect on protecting cells from damage by inhibiting production of p53 mRNA, and in DSSMS, by inhibiting production of p53 mRNA and p21 mRNA after hypoxia. DSTMT effectively blocked off Ca2+ at low density, but DSSMS effectively blocked off Ca2+ at high density. Both DSTMT and DSSMS had an effect on inhibiting lipid metabolism by blocking off production of apo B mRNA. Conclusions: These results suggest that DSTMT and DSSMS might be usefully applied for treatment of hyperlipidemia and suppression of brain damage.

• Food Science and Preservation
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• v.24 no.7
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• pp.1007-1016
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• 2017

Melania snail (Semisulcospira libertina) was traditionally used as the healthy food in Korea. It was generally known to improve liver function and heal a diabetes. The aim of this study was to elucidate the anti-diabetic mechanism of melanian snail hydrolysates treated with protamex (MPH) by investigating the inhibitory action on protein tyrosine phosphatase 1B (PTP1B), the improving effect on the insulin resistance in C2C12 myoblast and the protective effect for pancreatic beta-cell (INS-1) under the glucose toxicity. The melania snail hydrolysates treated with protamex (MPH), which showed the highest degree of hydrolysis (43%), and inhibited effectively PTP1B activity ($IC_{50}=15.42{\pm}1.1{\mu}g/mL$), of which inhibitory effect was higher than usolic acid, positive control ($IC_{50}=16.65{\mu}g/mL$). MPH increased the glucose uptake in C2C12 myoblast treated with palmitic acid. In addition, MPH increased insulin mRNA expression level by over 160% with enhanced cell viability in INS-1 cell under the high glucose concentration (30 mM). These results suggest that MHP may improve the diabetic symptom by the inhibiting the PTP1B activity, increasing the glucose uptake in muscle cell and protecting the pancreatic beta-cell from glucose toxicity.

• Journal of Food Hygiene and Safety
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• v.29 no.2
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• pp.85-91
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• 2014

Deoxynivalenol (DON) and related trichothecene mycotoxins are extensively distributed in the cereal-based food and feed stuffs worldwide. Recent climate changes and global grain trade increased chance of exposure to more DON and related toxic metabolites in poorly managed production systems. Monitoring the biological and environmental exposures to the toxins are crucial in protecting human and animals from toxicities of the hazardous contaminants in food or feeds. Exposure biomarkers including urine DON itself are prone to shift to less harmful metabolites by intestinal microbiota and liver metabolic enzymes. De-epoxyfication of DON by gut microbes such as Eubacterium strain BBSH 797 and Eubacterium sp. DSM 11798 leads to more fecal secretion of DOM-1. By contrast, most of plant-derived DON-glucoside is also easily catabolized to free DON by gut microbes, which produces more burden to body. Phase 2 hepatic metabolism also contributes to the glucuronidation of DON, which can be useful urine biomarkers. However, chemical modification could be very typical depending on the anthropologic or genetic background, luminal bacteria, and hepatic metabolic enzyme susceptibility to the toxins in the diet. After toxin exposure, effect biomarkers are also important in estimating the linkage and mechanisms of foodborne diseases in human and animal population. Most prominent adverse effects are demonstrated in the DON-induced immunological and behavioral disorders. For instance, acutely elevated interleukin-8 from insulted gut exposed to dietaty DON is a dominant clinical biomarker in human and animals. Moreover, subchronic exposure to the toxins is associated with high levels of serum IgA, a biological mediator of IgA nephritis. In particular, anorexia monitoring using mouse models are recently developed to monitor the biological activities of DON-induced feed refusal. It is also mechanistically linked to alteration of serotoin and peptide YY, which are promising biomarkers of neurological disorders by the toxins. As animal-alternative biomonitoring, huamn enterocyte-based assay has been developed and more realistic gut mimetic models would be useful in monitoring the effect biomarkers in resposne to toxic contaminants in the future investigations.