• Journal of Ginseng Research
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• v.45 no.2
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• pp.316-324
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• 2021

Background: Korea Red Ginseng (KRG) has been used as remedies with hepato-protective effects in liver-related condition. Microbiota related gut-liver axis plays key roles in the pathogenesis of chronic liver disease. We evaluated the effect of KRG on gut-liver axis in patients with nonalcoholic statohepatitis by the modulation of gut-microbiota. Methods: A total of 94 patients (KRG: 45 and placebo: 49) were prospectively randomized to receive KRG (2,000 mg/day, ginsenoside Rg1+Rb1+Rg3 4.5mg/g) or placebo during 30 days. Liver function test, cytokeraton 18, and fatigue score were measured. Gut microbiota was analyzed by MiSeq systems based on 16S rRNA genes. Results: In KRG group, the mean levels (before vs. after) of aspartate aminotransferase (53 ± 19 vs. 45 ± 23 IU/L), alanine aminotransferase (75 ± 40 vs. 64 ± 39 IU/L) and fatigue score (33 ± 13 vs. 26 ± 13) were improved (p < 0.05). In placebo group, only fatigue score (34 ± 13 vs. 31 ± 15) was ameliorated (p < 0.05). The changes of phyla were not statistically significant on both groups. In KRG group, increased abundance of Lactobacillus was related with improved alanine aminotransferase level and increased abundance of Clostridium and Intestinibacter was associated with no improvement after KRG supplementation. In placebo group, increased abundance of Lachnospiraceae could be related with aggravation of liver enzyme (p < 0.05). Conclusion: KRG effectively improved liver enzymes and fatigue score by modulating gut-microbiota in patients with fatty liver disease. Further studies are needed to understand the mechanism of improvement of nonalcoholic steatohepatitis. ClnicalTrials.gov: NCT03945123 (www.ClinicalTrials.gov).

• Toxicological Research
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• v.14 no.2
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• pp.129-141
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• 1998

Toxic effects of 2-bromopropane (2-BP) on the hematopoietic system and testis were investigated in male Srague-Dawley (SD) rats. 80 male SD rats, 5 weeks old, were treated with 2-BP in corn oil at levels of 0, 100, 330 and 1,000 mg/kg/day for 4 weeks orally. 10 animals from each group were maintained for additional 8 weeks following the treatment. In addition, 60 male SD rats were divided into 2 groups and administered 2-BP in corn oil at levels of 0 and 1,000 mg/kg/day orally and sacrificed after 1. 2 and 3 weeks of treatment. Clinical observation. body weight changes, food consumption, organ weight changes. hematology, serum chemistry and histopathology of the testis were performed in the study. No clinical sign and mortality were observed in the study. The body weights were significantly reduced with the treatment but gradually recovered. The relative organ weights of the testis and thymus significantly decreased in both of the groups treated with 1,000 mg/kg/day for 3 and 4 weeks. In the recovery groups, organ weights of the testis and epididymis were significantly reduced in both of the groups treated with 330 and 1,000 mg/kg/day. Platelets and reticulocytes were significantly reduced in both of the group treated with 1.000 mg/kg/day for 3 and 4 weeks. While red blood cells were de-creased but mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) were increased in the recovery group. Significant increase of chloride was observed in all of the treatment groups except the recovery groups, and calcium was significantly increased in both of the groups treated with 1,000 mg/kg/ day for 3 and 4 weeks. On the other hand. there were significant decreases in alanine aminotransferase (ALT) and aspatate aminotransferase (AST) in most of groups treated with 1.000 mg/kg/day. In the testis. the spermatogonia in stages I-VI were mostly depleted and the spermatocytes in stages VII-VIII were de-generated or necrotized at week 1 after treatment of 2-BP. The degeneration of germ cells and the a-trophy of seminiferous tubules became more severe in time-dependent and dose-dependent manners. The damaged tubules showed regeneration in part. however. they did not appear to be completely recovered within 8 weeks of the recovery period. On the basis of the results. it is suggested that 2-BP would cause toxicities in hematopoiesis by possibly interfering the production of red blood cells and platelets and in spermatogenesis by the destruction oj spermatogonia in SD male rats.

• Korean Journal of Environmental Biology
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• v.35 no.2
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• pp.128-133
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• 2017

To determine the optimum water temperature (a temperature which minimizes metabolic activities and stress in fish) for long distance transportation of red-spotted grouper (Epinephelus akaara), by evaluating the behavior, survival and physiological and hematological responses to variable water temperature conditions (9, 12, 15, 18 and $21^{\circ}C$) for 48 hours. Fish exposed to $9^{\circ}C$ died at 48 hours exposure, but those exposed to 12, 15, 18 and $21^{\circ}C$ treatment groups all survived. Fish in the 15, 18 and $21^{\circ}C$ exposure groups exhibited normal swimming, while those exposed to $12^{\circ}C$ were observed to be stationary at the bottom of the tank. The plasma cortisol and glucose concentration were higher in fish exposed to $12^{\circ}C$ than at other temperature conditions. The fish in the 12 and $15^{\circ}C$ groups had significantly higher hematocrit (Ht) and hemoglobin (Hb) than those in the 18 and $21^{\circ}C$ groups (P<0.05). Levels of aspartate aminotransferase (AST), $NH_3$ and osmolality showed a pattern similar to the levels of plasma cortisol, while alanine aminotransferase (ALT) and total protein did not significantly vary among the experimental groups. These results indicate that the optimum water temperature for long distance transportation of the red-spotted grouper is $15^{\circ}C$.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.5
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• pp.1789-1794
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• 2015

Background: Non-alcoholic fatty liver disease (NAFLD), the most common liver problem in diabetes, is a risk factor for liver cancer. Diabetes, high body mass index (BMI) and old age can all contribute to NAFLD progression. Transient elastography (TE) is used for non-invasive fibrosis assessment. Objectives: To identify the prevalence of NAFLD and significant hepatic fibrosis in diabetic patients and to assess associated factors. Materials and Methods: One hundred and forty-one diabetic and 60 normal subjects were screened. Fatty liver was diagnosed when increased hepatic echogenicity and vascular blunting were detected by ultrasonography. Liver stiffness measurement (LSM) representing hepatic fibrosis was assessed by TE. LSM ${\geq}7$ kPa was used to define significant hepatic fibrosis. Results: Four cases were excluded due to positive hepatitis B viral markers and failed TE. Diabetic patients had higher BMI, systolic blood pressure, waist circumference and fasting glucose levels than normal subjects. Fatty liver was diagnosed in 82 (60.7%) diabetic patients but in none of the normal group. BMI (OR: 1.31; 95%CI: 1.02-1.69; p=0.038) and alanine aminotransferase (ALT)(OR: 1.14; 95%CI: 1.05-1.23; p=0.002) were associated with NAFLD. Diabetic patients with NAFLD had higher LSM than those without [5.99 (2.4) vs 4.76 (2.7) kPa, p=0.005)]. Significant hepatic fibrosis was more common in diabetic patients than in normal subjects [22 (16.1%) vs 1 (1.7%), p=0.002]. Aspartate aminotransferase (AST)(OR: 1.24; 95%CI: 1.07-1.42; p=0.003) was associated with significant hepatic fibrosis. Conclusions: Sixty and sixteen percent of diabetic patients were found to have NAFLD and significant hepatic fibrosis. High BMI and ALT levels are the predictors of NAFLD, and elevated AST level is associated with significant hepatic fibrosis.

• Journal of Nutrition and Health
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• v.48 no.5
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• pp.390-397
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• 2015

Purpose: In this study, we investigated the effects of chronic alcohol and excessive iron intake on mitochondrial DNA (mtDNA) damage and the progression of alcoholic liver injury in rats. Methods: Twenty-four Sprague-Dawley male rats were divided into four groups (Control, EtOH, Fe, and EtOH + Fe), and fed either control or ethanol (36% of total calories) liquid diet with or without 0.6% carbonyl iron for eight weeks. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, liver malondialdehyde concentrations were measured by colorimetric assays. Liver histopathology was examined by Hematoxylin-eosin staining of the fixed liver tissues. The integrity of the hepatic mtDNA and nuclear DNA was measured by long-range PCR. The gene expression levels of cytochrome c oxidase subunit 1 (Cox1) and NADH dehydrogenase subunit 4 (Nd4) were examined by real-time PCR. Results: Serum ALT and AST activities were significantly higher in the EtOH+Fe group, as compared to the Control group. Similarly, among four groups, liver histology showed the most severe lipid accumulation, inflammation, and necrosis in the EtOH + Fe group. PCR amplification of near-full-length (15.9 kb) mtDNA showed more than 50% loss of full-length product in the liver of the EtOH + Fe group, whereas amounts of PCR products of a nuclear DNA were unaffected. In addition, the changes in the mtDNA integrity showed correlation with reductions in the mRNA levels of mitochondrial gene Cox1 and Nd4. Conclusion: Our data suggested that the liver injury associated with excessive iron and alcohol intake involved mtDNA damage and corresponding mitochondrial dysfunction.

• Journal of Pharmacopuncture
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• v.2 no.1 s.2
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• pp.111-133
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• 1999

These studies were carried out to investigate the effect of Herbal-acupuncture with Inzinsammultang extract on the recovery from liver injury of rats. The liver injury of rats induced with 0.3ml/ea carbon tetrachloride. The Herbal-acupunture with Inzinsam multang extract solution inserted into corresponding focus of Kansu(BL18) in rats. In this study, SD-Rats(Sprague-Dawley) were divided into 4 groups ; Normal group (None treated group), Control-group(The group not treated after $CCI_4$-intoxication), Treated group; Example I-group(Saline-injected groups after $CCl_4$-intoxication) and Example II-group(Inzinsammultang-injected groups after $CCl_4$-intoxication). Through histological observation, Example II-group sho-ws that liver injury is weaker than Control group.(p<0.05) Biochemical assays for each serum enzyme activities of AST, ALT and LDH, levels of albumin, ${\gamma}$-GT, TG, total cholesterol were performed. The results were summarized as follows 1. AST(Aspartate aminotransferase) activity in serum significantly decreased in the Inzinsammultang-injected groups after $CCl_4$-intoxication. Inzinsammultang-injected groups after $CCl_4$-intoxication showed significantly higher AST activities, compared with the Saline-injected groups after $CCl_4$-intoxication.(p<0.05) 2. ALT(Alanine aminotransferase) activity in serum significantly decreased in the Inzinsammultang-injected groups after $CCl_4$-intoxication. The Inzinsammultang-injected groups after $CCl_4$-intoxication showed significantly higher AST activities, compared with the Saline-injected groups after $CCl_4$-intoxication(p<0.05) 3. Level of Albumin in serum significantly increased in the Inzinsarnmultang-injected groups after $CCl_4$-intoxication. 4. LDH(Lactate dehydrogenase) activities in serum significantly decreased in the Inzinsammultang-injected groups after $CCl_4$-intoxication.(p<0.05) 5. ${\gamma}$-GT(Glutamyl transferase) in serum significantly decreased in the Inzinsammultang-injected groups after $CCl_4$-intoxication(p<0.05) 6. As for the TG(Triglyceride) levels in serum, Inzinsammultang-injected groups after $CCl_4$-intoxication is no significant differences compared with the Saline-injected groups after $CCl_4$-intoxication.(p<0.05) 7. Total cholesterol in serum significantly increased in the Inzinsarnmultang-injected groups after $CCl_4$-intoxication.(p<0.05) Those results indicate that the Inzinsammultang Herbal-acupuncture have significant effects on the liver injury induced by $CCl_4$. So it is expected that the Inzinsammultang Herbal-acupuncture can be used to cure inflammations and recover the functions of damaged liver cells.

• Journal of the Korean Society of Food Science and Nutrition
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• v.31 no.1
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• pp.124-130
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• 2002

The present study was carried out to investigate the pretreatment of effects of water extract obtained from Eucommia ulmoides leaf (ELE) on hepatotoxicity of carbon tetrachloride ($CCl_4$) -treated rats. Thirty two healthy male Sprague-Dawley rats were divided into four groups, i.e. normal group (N), $CCl_4$-treated group (T), ELE-treated group (E), and ELE-treated group after injection of $CCl_4$(TE). The administration of $CCl_4$increased the activities of aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase in serum, but their activities were significantly decreased by the addition of ELE. Alkaline phosphatase activity in serum was significantly decreased in $CCl_4$-treated group, while the activity was not decreased by the extracts. Higher levels of HDL cholesterol was found in E and TE group which showed lower levels of total and LDL-cholesterol. Histopathologic findings by light microscopic examination showed fatty change, ballooning degeneration, acidophilic degeneration, spotty necrosis and zonal necrosis in $CCl_4$treated liver tissue. But the degree of liver damage was not identified in liver tissue of the TE group. These results indicated that Eucommia ulmoides leaf water extracts led migtigation of liver demage induced with $CCl_4$.

• Journal of Food Hygiene and Safety
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• v.18 no.4
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• pp.177-182
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• 2003

Saururus chinensis Baill (Saururaceae) is a perennial plant that has been used for therapy of edema, jaundice and gonorrhea in Korean folk medicine. This study was carried out to investigate the inhibitory effects of Saururus chinensis Baill(SCB) on hepatoprotective effects in accutely Carbone Tetrachloride ($CCl_4$) treated rats. Saururus chinensis Baill (100 mg/kg) was administered into rats intraperitoneally for 2 weeks, after the injection of CCl4 (3.3 ml/kg). We dxamined the biochemical parameters by measuring the levels of Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Total cholesterol, Triglyceride (TG), HDL-cholesterol, and LDL-cholesterol in serum and Malonedialdehyde (MDA) in liver tissue of rats. cholesterol was siginificantly elevated in $CCl_4$-treated abnormal group (CTA). The higher level of HDL-cholesterol was found is Saururus chinensis Baill and CCl4 administered group (SCT), which showed the lower levels of Total-cholesterol and LDL-cholesterol. TG content in the SCT was decreased compared to CTA by 0.93 times. MDA content in the SCT was inhibited compared to CTA by 33.00%. These findings indicate that Saururus chinensis. Baill may have a protective effect against CCl4-treated hepatotoxicity in rats.

• Food Science and Preservation
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• v.23 no.2
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• pp.275-282
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• 2016

STAR of STAR (SS 01-04) is a series of drinks that consist of various extracts obtained from Coriolus versicolor, Artemisia capillaris Thunb., Hovenia dulcis, Acanthopanax sessiliflorus, Lycium chinense, Citrus reticulata, Saururus chinensis, Pueraria lobata, Pyrus pyrifolia, and Oenanthe javanica. A purpose of this study was to investigate the hepatoprotective effect of SS 01-04. Antioxidant activity of the drinks was evaluated by conducting a hydroxyl radical-scavenging assay. Cytotoxicity and hepatoprotective potential were determined using HepG2 cells in vitro, while protective effects against acute hepatotoxicity was evaluated in vivo. The antioxidant activity of the SS 01-04 at concentration of 100 and 250 mg/mL was similar to that of $50{\mu}M$ vitamin C. tert-Butyl hydroperoxide (tBHP)-induced production of reactive oxygen species (ROS) was blocked by SS 01, 03 and 04 in a dose-dependent manner. Treatment with SS 04 significantly lowered the serum levels of alanine aminotransferase and aspartate aminotransferase in an animal model of carbon tetrachloride $(CCl_4)-induced$ hepatotoxicity (p<0.05). In addition, SS04 increased glutathione level while decreased malondialdehyde level in the liver considerably (p<0.05). It also inhibited the $CCl_4-induced$ increase in the levels of triglyceride and cholesterol in serum and the liver. These findings indicated that SS 01-04 possessed antioxidant activity and protect against ROS. In particular, SS 04 is potentially highly beneficial in treating liver damage as it scavenges reactive free radicals and boosts the endogenous antioxidant system.

• Clinical and Experimental Pediatrics
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• v.58 no.6
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• pp.211-217
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• 2015

Purpose: Mycoplasma pneumoniae (MP) infection is a major cause of respiratory infection in school-aged children. Extrapulmonary manifestations of MP infection are common, but liver involvement has been rarely reported. The aim of this study was to determine the clinical characteristics of MP-associated hepatitis. Methods: This prospective study included 1,044 pediatric patients with MP infection diagnosed serologically with MP IgM at one medical center from January 2006 to December 2012. Eighty of these patients had elevated levels of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT), each greater than 50 IU/L, without any other specific liver disorder and were compared with the 964 children without liver disorders. Results: In total, 7.7% of patients with MP infection had a diagnosis of hepatitis, especially in fall and winter. The ratio of male to female patients was 1.7:1, and the mean age of the patients was 5 years and 5 months. The most common symptoms were cough, fever, and sputum. Anorexia was the most common gastrointestinal symptom, followed by nausea/vomiting, diarrhea, and abdominal pain. Mean levels of AST and ALT were 100.65 IU/L and 118.73 IU/L, respectively. Serum AST/ALT level was normalized within 7.5 days on average without complications. The mean duration of hospitalization (11.3 days) was longer for children with hepatitis than for those without hepatitis (P=0.034). Conclusion: MP-associated hepatitis is not uncommon and has a relatively good prognosis. Therefore, clinicians should be concerned about liver involvement in MP infection but avoid further unnecessary evaluation of hepatitis associated with MP.