• Yonsei Medical Journal
• /
• v.59 no.9
• /
• pp.1064-1071
• /
• 2018

Purpose: To explore the influence of S100 calcium binding protein A4 (S100A4) knockout (KO) on methionine-choline-deficient (MCD) diet-induced non-alcoholic fatty liver disease (NAFLD) in mice. Materials and Methods: S100A4 KO mice (n=20) and their wild-type (WT) counterparts (n=20) were randomly divided into KO/MCD, Ko/methionine-choline-sufficient (MCS), WT/MCD, and WT/MCS groups. After 8 weeks of feeding, blood lipid and liver function-related indexes were measured. HE, Oil Red O, and Masson stainings were used to observe the changes of liver histopathology. Additionally, expressions of S100A4 and proinflammatory and profibrogenic cytokines were detected by qRT-PCR and Western blot, while hepatocyte apoptosis was revealed by TUNEL staining. Results: Serum levels of aminotransferase, aspartate aminotransferase, triglyceride, and total cholesterol in mice were increased after 8-week MCD feeding, and hepatocytes performed varying balloon-like changes with increased inflammatory cell infiltration and collagen fibers; however, these effects were improved in mice of KO/MCD group. Meanwhile, total NAFLD activity scores and fibrosis were lower compared to WT+MCD group. Compared to WT/MCS group, S100A4 expression in liver tissue of WT/MCD group was enhanced. The expression of proinflammatory ($TGF-{\alpha}$, $IL-1{\beta}$, IL-6) and profibrogenic cytokines ($TGF-{\beta}1$, COL1A1, ${\alpha}-SMA$) in MCD-induced NAFLD mice were increased, as well as apoptotic index (AI). For MCD group, the expressions of proinflammatory and profibrogenic cytokines and AI in KO mice were lower than those of WT mice. Conclusion: S100A4 was detected to be upregulated in NAFLD, while S100A4 KO alleviated liver fibrosis and inflammation, in addition to inhibiting hepatocyte apoptosis.

• Animal Bioscience
• /
• v.34 no.3_spc
• /
• pp.405-416
• /
• 2021

Objective: This study evaluated the effects of feeding diets naturally contaminated with deoxynivalenol (supplemental 2 mg/kg) on health, growth, and the effects of a mycotoxin-detoxifying additive in newly-weaned pigs. Methods: Thirty-six pigs (27 day-old) were housed individually and assigned to 3 treatments for 5 weeks: CON (diet containing minimal deoxynivalenol), MT (diet with supplemental 1.9 mg/kg of deoxynivalenol), and MT+D (MT + mycotoxin-detoxifying additive, 0.2%, MegaFix, ICC, São Paulo, Brazil). The mycotoxin-detoxifying additive included bentonite, algae, enzymes, and yeast. Blood was taken at week 2 and 5. Jejunal tissue were taken at week 5. Data were analyzed using the MIXED procedure of SAS. Results: Pigs fed MT+D tended to have decreased (p = 0.056) averaged daily feed intake during week 1 than MT. At week 2, serum aspartate aminotransferase/alanine aminotransferase in MT tended to be lower (p = 0.059) than CON, whereas it was increased (p<0.05) for MT+D than MT, indicating hepatic damages in MT and recovery in MT+D. Pigs fed MT had lower (p<0.05) blood urea nitrogen/creatinine than CON, supporting hepatic damage. At week 5, pigs fed MT tended to have reduced (p = 0.079) glucose than CON, whereas it was increased (p<0.05) for MT+D than MT, indicating impaired intestinal glucose absorption in MT, which was improved in MT+D. Pigs fed CON tended to have increased (p = 0.057) total glutathione in jejunum than MT, indicating oxidative stress in MT. Pigs fed MT+D had a reduced (p<0.05) proportion of Ki-67-positive cells in jejunum than MT, indicating lower enterocyte proliferation in MT+D. Conclusion: Feeding supplemental 1.9 mg/kg of deoxynivalenol reduced growth and debilitated hepatic health of pigs, as seen in leakage of hepatic enzymes, impaired nitrogen metabolism, and increase in oxidative stress. The mycotoxin-detoxifying enhanced hepatic health and glucose levels, and attenuated gut damage in pigs fed deoxynivalenol contaminated diets.

• The Korea Journal of Herbology
• /
• v.36 no.1
• /
• pp.1-8
• /
• 2021

Objective : Citri Unshius Pericarpium (Citrus unshiu peel) has been used in Korean medicine to treat indigestion, vomiting, coughing and phlegm. This study investigated the hepatoprotective effect of ethanol extract of Citrus unshiu peel (CEE) in cadmium (CdCl2)-treated mouse model. Methods : CEE was dissolved in water and administered orally to mice once a day for 7 consecutive days. The mice were then exposed to a single intraperitoneal (i.p.) injection of cadmium (4 mg/kg body weight) to induce acute hepatotoxicity. At the end of the experiment, blood and liver tissue samples were collected, analyzed for alanine aminotransferase (ALT), aspartate aminotransferase (AST), and histopathological evaluation. Liver damage was assessed as the percentage of degenerative areas of the hepatic parenchyma, the number of degenerative hepatocytes, and the number of infiltrated inflammatory cells. Results : In cadmium-treated rats, pretreatment with CEE significantly reduced the serum ALT and AST levels associated with liver damage. Histopathologically, CEE prevented degenerative changes on the hepatic tissues including confluent necrosis, congestions and infiltration of inflammatory cells. CEE also reduced the elevation of oxidative stress markers (nitrotyrosine and 4-hydroxynonenal) and apoptosis markers (cleaved caspase-3 and cleaved PARP) positive cells. PARP protein expression in liver tissue was also restored by CEE. Conclusion : This study showed that CEE exerted antioxidant and anti-apoptotic effects against cadmium-induced liver injury. Thus, it can be concluded that CEE can be used to prevent liver damage caused by cadmium.

• Journal of Gastric Cancer
• /
• v.21 no.1
• /
• pp.74-83
• /
• 2021

Purpose: No consensus exists on whether to preserve or ligate an aberrant left hepatic artery (ALHA), which is the most commonly encountered hepatic arterial variation during gastric surgery. Therefore, we aimed to evaluate the clinical effects of ALHA ligation by analyzing the perioperative outcomes. Materials and Methods: We retrospectively reviewed the data of 5,310 patients who underwent subtotal/total gastrectomy for gastric cancer. Patients in whom the ALHA was ligated (n=486) were categorized into 2 groups according to peak aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels: moderate-to-severe (MS) elevation (≥5 times the upper limit of normal [ULN]; MS group, n=42) and no-to-mild (NM) elevation (<5 times the ULN; NM group, n=444). The groups were matched 1:3 using propensity score-matching analysis to minimize confounding factors that can affect the perioperative outcomes. Results: The mean operation time (P=0.646) and blood loss amount (P=0.937) were similar between the 2 groups. The length of hospital stay was longer in the MS group (13.0 vs. 7.8 days, P=0.022). No postoperative mortality occurred. The incidence of grade ≥ IIIa postoperative complications (19.0% vs. 5.1%, P=0.001), especially pulmonary complications (11.9% vs. 2.5%, P=0.003), was significantly higher in the MS group. This group also showed a higher Comprehensive Complication Index (29.0 vs. 13.9, P<0.001). Conclusions: Among patients with a ligated ALHA, those with peak AST/ALT ≥5 times the ULN showed worse perioperative outcomes in terms of hospital stay and severity of complications. More precise perioperative decision-making tools are needed to better determine whether to preserve or ligate an ALHA.

• The Korea Journal of Herbology
• /
• v.36 no.2
• /
• pp.11-17
• /
• 2021

Objective : This study was conducted to investigate the effects of Effects of Akebia quinata (AQ) extract on alcohol-induced damage of liver, spleen and thymus in rats. Method : Experimental animals were divided in to 4 groups; Normal group, Alcohol group, AQ50 group and AQ200 group. All rats, except for Normal group, were fed 25 % ethanol for 55 days. During experimental period, Normal group and Alcohol group were administrated saline, and AQ50 group and AQ200 group were administrated AQ extract at dose of 50 and 200 mg/kg/day, respectively. We measured organ weight, liver triglyceride contents, and alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and triglycerid levels in serum. Also, we conducted histomorphometry and histopathological observation of liver, spleen and thymus. Results : AQ significantly decreased the level of AST, ALT and triglyceride in serum and the liver triglyceride contents induced by ethanol. Also, AQ significantly inhibited lipid droplets accumulation in hepatocytes. The decreased relative organ weight of spleen and thymus by ethanol were increased by AQ administration. In histopathological analysis of spleen, the rats administrated AQ 200 mg/kg presented significantly increased mean diameters of white pulps, numbers of white pulps and splenic thicknesses. The administration of 200 mg/kg AQ improved decreased lobular thickness and cortex thickness of thymus, which were decreased by ethanol. Conclusions : The results of present study indicated that AQ has an ameliorating effect for fatty degeneration of liver and damage of spleen and thymus.

• Nutrition Research and Practice
• /
• v.15 no.2
• /
• pp.173-186
• /
• 2021

BACKGROUD/OBJECTIVES: Alzheimer's disease (AD) is the most common cause of dementia in the elderly. Due to the increased incidence of dementia, there is a corresponding increase concerning the importance of AD. In this study, we investigated the protective effects conferred by Zizyphus jujuba (Zj) and Zizyphus jujuba fermented by yeast (Zj-Y), on cognitive impairment in an AD mouse model. MATERIALS/METHODS: AD was induced by injecting amyloid beta25-35 (Aβ25-35) in ICR mice, and subsequently 200 mg/kg Zj or Zj-Y was administered daily for 14 days. The cognitive ability of AD mice was observed through behavioral experiments in T-maze, novel object recognition, and Morris water maze tests. We subsequently measured the levels of malondialdehyde (MDA), nitric oxide (NO), aspartate aminotransferase, and alanine aminotransferase in either tissues or serum. RESULTS: In behavioral tests, deterioration was revealed in the short- and long-term learning and memory functions in the Aβ25-35-injected control group compared to the normal group, indicating that Aβ25-35 injection impairs cognitive functions. However, administration of Zj and Zj-Y improved cognitive function in mice, as compared to the Aβ25-35-injected control mice. In addition, the Aβ25-35 induced elevations of MDA and NO in the brain, kidney, and liver were suppressed after exposure to Zj and Zj-Y. Especially, Zj-Y showed stronger scavenging effect against MDA and NO, as compared to Zj. CONCLUSIONS: Results of the present study indicate that Zj-Y exerts a protective effect on cognitive impairment and memory dysfunction, which is exerted by attenuating the oxidative stress induced by Aβ25-35.

• The Korea Journal of Herbology
• /
• v.28 no.2
• /
• pp.17-23
• /
• 2013

Objectives : To investigate the hepatoprotective effect of Gardeniae Fructus (Ga) and Glycine semen preparatum (Gl) aqueous extract against D-galactosamine (D-GalN, 300mg/kg body weight) was administered to the male Sprague Dawley (SD) rats. Materials and Methods : The study was carried out on male SD rats (age matched, weight $250{\pm}10$ g). Experimental groups (Exp) divided four : Normal group (Nor) was administered saline, Control (Con) group was only received D-GalN (300 mg/kg) intraperitoneally. Exp was orally administered Ga (200 mg/kg; Ga group), Gl (700 mg/kg; Gl group), and Chizadochi-Tang (200 mg/kg+700 mg/kg, GG group) after D-GalN treatment during 14 days (n=6). Results : D-GalN administration induced hepatotoxicity in rats which was manifested by increased levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) but decreased total cholesterol (HDL C) and triglyceride (TG). The serum TG concentrations were significantly increased ($^{\sharp}p$ <0.05) in the Ga group compared with Con. AST and ALP activities were significantly decreased ($^{\sharp}p$ <0.05) in the all experimental groups compared with Con. ALT activities were significantly decreased ($^{\sharp}p$ <0.05) in the Ga group compared with Con. LDH activities were significantly decreased ($^{\sharp}p$ <0.05) in the GG group compared with Con. On the light microscopic study, a number of vacuole were observed in the Con, but decreased in experimental groups. Conclusion : Ga aqueous extract and Chizadochi-Tang extract possesses hepatoprotective potential, thus validating its use in alleviating toxic effects of D-GalN.

• Nutrition Research and Practice
• /
• v.16 no.3
• /
• pp.344-353
• /
• 2022

BACKGROUND/OBJECTIVES: Hydrolyzed formula is often fed to infants with gastrointestinal or immune issues, such as malabsorption or cow's milk allergy, because enzymatic treatment has rendered it more digestible and less allergenic than standard cow's milk formula (SF). Partially hydrolyzed formula (PHF) should be considered for those infants who are intolerant to extensively hydrolyzed formula. However, there are concerns about the nutritional insufficiencies of PHF. We aimed to evaluate the effects of PHF on the growth and health indicators in infants who were at high-risk of allergic disease and potential candidates for consuming PHF. SUBJECTS/METHODS: A total of 83 infants aged 0-2 mon with a family history of allergies were assigned to consume either PHF or SF until 24 weeks of age. Anthropometric measures were obtained at baseline, 12 weeks, and 24 weeks; blood samples were drawn and evaluated at the end of the study. RESULTS: No significant differences were observed in weight, height, and weight-for-height at any time point in each sex between the PHF and SF groups. At 24 weeks of age, the weight-for-age and height-for-age z-scores of the SF group were higher than those of the PHF group, but there was no significant difference in the weight-for-height z-score. There were no significant differences in levels of white blood cells, hemoglobin, ferritin, protein, albumin, aspartate aminotransferase, alanine aminotransferase, eosinophil cationic protein, and immunoglobulin E. CONCLUSIONS: In this study, there were no differences in growth and blood panels between the infants consuming PHF or SF. Therefore, infants who are unable to tolerate SF can be fed PHF without nutritional concerns about growth.

• Nutrition Research and Practice
• /
• v.17 no.6
• /
• pp.1113-1127
• /
• 2023

BACKGROUND/OBJECTIVES: Excessive alcohol consumption has harmful health effects, including alcohol hangovers and alcohol-related liver disease. Therefore, methods to accelerate the alcohol metabolism are needed. Laurus nobilis is a spice, flavoring agent, and traditional herbal medicine against various diseases. This study examined whether the standardized aqueous extract of L. nobilis leaves (LN) accelerates the alcohol metabolism and protects against liver damage in single-ethanol binge Sprague-Dawley (SD) rats. MATERIALS/METHODS: LN was administered orally to SD rats 1 h before ethanol administration (3 g/kg body weight [BW]) at 100 and 300 mg/kg BW. Blood samples were collected 0.5, 1, 2, and 4 h after ethanol administration. The livers were excised 1 h after ethanol administration to determine the hepatic enzyme activity. The alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities in the liver tissue were measured. RESULTS: LN decreased the serum ethanol and acetaldehyde levels in ethanol-administered rats. LN increased the hepatic ADH and ALDH activities but decreased the alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transferase activities in the ethanol-administered rats. In addition, LN inhibited lipid peroxidation and increased the activities of SOD and GPx. CONCLUSIONS: LN modulates the mediators of various etiological effects of excessive alcohol consumption and enhances the alcohol metabolism and antioxidant activity, making it a potential candidate for hangover treatments.

• Journal of Veterinary Clinics
• /
• v.41 no.1
• /
• pp.30-36
• /
• 2024

A 3-year-old, 20.6 kg, neutered male German Shepherd dog was referred to Kyungpook National University Veterinary Medicine Teaching Hospital. Clinical examination revealed chronic diarrhea for 6 weeks and a non-tender, distended abdomen without lethargy, anorexia, and vomiting. Diarrhea was watery and had a waxing and waning course despite symptomatic treatment. A complete blood count identified mild leukocytosis and mild anemia. Serum biochemistry analysis showed elevated alanine aminotransferase and aspartate aminotransferase levels, and mild hypoalbuminemia. Abdominal ultrasound examination revealed mixed echogenicity with absent blood flow at the caudate process of the caudate liver lobe and a small amount of ascites. Computed tomography revealed torsion of the caudate process of the caudate liver lobe and spleen and gas dilatation of the intestine. After establishing a diagnosis of organ torsion on imaging, we deemed the condition an emergency and immediately performed surgery. Given that laparotomy confirmed organ torsion, liver lobectomy, total splenectomy, and prophylactic gastropexy were conducted. The patient was discharged 11 days after surgery without complications. In general, liver lobe torsion and splenic torsion are uncommon in dogs and present with nonspecific clinical signs, such as abdominal pain, lethargy, anorexia, and vomiting. In the current case, torsion of the caudate liver lobe and spleen occurred without other clinical signs except for a distended abdomen. Moreover, no reports in dogs have demonstrated the simultaneous occurrence of both diseases.