• The Journal of Korean Medicine
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• v.31 no.5
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• pp.124-135
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• 2010

Background and Objective: Atherosclerosis is a diffuse, systemic disease that affects the coronary, cerebral, and peripheral arterial trees. Clopidogrel is widely used antiplatelet agent and its efficacy has been proven in cardiac and extracardiac vascular diseases, but it has several side effects. Therefore we investigated whether Sopunghwalhyeoltang, which is widely used for treating the blood stasis syndrome in traditional medicine, could decrease the side effect of antiplatelets and have a synergic effect. Methods & Materials: Male $ApoE^{(-/-)}$ mice were randomly divided into three different experimental groups, non-treated group (Control group), clopidogrel-treated group (CP group) and clopidogrel with Sopunghwalhyeol-tang treated group (CPS group). The control group was fed with only an atherogenic diet, the CP group an atherogenic diet plus clopidogrel 25mg/kg and the CPS group an atherogenic diet plus clopidogrel 25mg/kg with Sopunghwalhyeol-tang 100 mg/kg. We investigated plasma lipids with liver function test, and performed a histological investigation of liver and abdominal aorta. Results: 1. Photomicrographs of liver and abdominal aorta tissue showed lower histological injury and lipid accumulation in the CP and CPS groups than those in the Control group. 2. In the CPS group, plasma triglyceride level was significantly lower than in the Control and CP groups. 3. In the CPS group, the plasma aspartate aminotransferase (AST) level was significantly lower than in the CP group. Conclusions: The above results shows that a combined treatment of Sopunghwalhyeol-tang and clopidogrel have a synergic effect through inhibiting vessel injury and decrease the side effects of clopidogrel alone.

• Applied Microscopy
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• v.33 no.4
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• pp.299-313
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• 2003

The aim of the present study was to assess the role of protein kinase C (PKC) in the development of cardiac injury following scald burn. Sprague-Dawley rats were induced a scald burn a 15% total body surface area. Phorbol 12-myristate 13-acetate (PMA, 2 mg/kg) and bisindolylmaleimide (BIS, 0.05 mg/kg) were immediately administered i.p. after burn injury. 5 h and 24 h later, heart was removed and examined biochemical assay, ultrastructural changes and stereological analysis. The activity of serum aspartate aminotransferase was significantly increased at 5h (p<0.01) and 5h+BIS (p<0.001) after burn compared with that of control. The activity of serum creatinine was significantly decreased in PMA-treated groups after burn compared with postburn 5 h. PMA caused a decrease in MPO activity and induced wavy fibers in cardiac myocytes at postburn 5 and 24h. BIS induced contraction band, separation of intercalated disk and abnormal mitochondria in cardiac myocytes at postburn 5 and 24h. In stereological analysis, treatment of rats with PMA increased volume density of myofibril and mitochondria compared with postburn 5 and 24h. Our data suggest that the activation of PKC in scald burned heart decreases inflammation and protects the myocardium.

• Korean Journal of Veterinary Service
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• v.40 no.2
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• pp.107-117
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• 2017

This study was conducted to investigate of hepatoprotective effect of dandelion water extract (DWE) according to repeated administration of thioacetamide (TAA) induced hepatotoxicity in Spraque-Dawley rats. Thirty rats were randomly assigned to 5 groups; normal control, DWE-control, TAA-control (TAA injection during the feeding of normal diet), TAA&DWE600 (TAA repeated injection during the feeding of DWE 600 mg/kg BW), TAA&DWE1200 (TAA repeated injection during the feeding of DWE 1,200 mg/kg BW). Rats in DWE-control and TAA&DWE groups were treated with DWE (600 or 1,200 mg/kg BW daily) by gavage for 20 days (twice a day). All the rats in the TAA-control and TAA&DWE groups were repeated injection of TAA (100 mg/kg BW) into the abdominal cavity 3 days interval and 12 hrs later, all rats were sacrificed. At the same time, normal control and DWE-control groups were injected normal saline. In TAA&DWE groups, serum alanine and aspartate aminotransferase (ALT, AST) were significantly decreased and triglyceride (TG) synthesis was significantly increased compared to TAA group. As well as total billilubin and GGT were slightly decreased by the treatment of DWE. Lipid peroxidation (MDA) concentration was significantly decreased and hepatic GSH content was slightly or significantly increased in the TAA&DWE groups compared to TAA group. Hepatic anti-oxidative enzyme activities, such as GSH, GST, SOD and catalase were slightly or significantly elevated by the treatment of DWE. According to these results, When dandelion extract was long term supplied, it could be used as a potential protective material for a longer time liver damage by repeated adminstration of the TAA.

• Journal of Gastric Cancer
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• v.17 no.2
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• pp.132-144
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• 2017

Purpose: To identify baseline prognostic factors for survival in patients with disease progression, during or after chemotherapy for the treatment of advanced gastric or gastroesophageal junction (GEJ) cancer. Materials and Methods: We pooled data from patients randomized between 2009 and 2012 in 2 phase III, global double-blind studies of ramucirumab for the treatment of advanced gastric or GEJ adenocarcinoma following disease progression on first-line platinum- and/or fluoropyrimidine-containing therapy (REGARD and RAINBOW). Forty-one key baseline clinical and laboratory factors common in both studies were examined. Model building started with covariate screening using univariate Cox models (significance level=0.05). A stepwise multivariable Cox model identified the final prognostic factors (entry+exit significance level=0.01). Cox models were stratified by treatment and geographic region. The process was repeated to identify baseline prognostic quality of life (QoL) parameters. Results: Of 1,020 randomized patients, 953 (93%) patients without any missing covariates were included in the analysis. We identified 12 independent prognostic factors of poor survival: 1) peritoneal metastases; 2) Eastern Cooperative Oncology Group (ECOG) performance score 1; 3) the presence of a primary tumor; 4) time to progression since prior therapy <6 months; 5) poor/unknown tumor differentiation; abnormally low blood levels of 6) albumin, 7) sodium, and/or 8) lymphocytes; and abnormally high blood levels of 9) neutrophils, 10) aspartate aminotransferase (AST), 11) alkaline phosphatase (ALP), and/or 12) lactate dehydrogenase (LDH). Factors were used to devise a 4-tier prognostic index (median overall survival [OS] by risk [months]: high=3.4, moderate=6.4, medium=9.9, and low=14.5; Harrell's C-index=0.66; 95% confidence interval [CI], 0.64-0.68). Addition of QoL to the model identified patient-reported appetite loss as an independent prognostic factor. Conclusions: The identified prognostic factors and the reported prognostic index may help clinical decision-making, patient stratification, and planning of future clinical studies.

• Journal of Animal Science and Technology
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• v.52 no.6
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• pp.505-511
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• 2010

Thirty six Hanwoo steers (average BW, $564.5\;{\pm}\;25.7\;kg$; average age, approximately 23 months) were used to evaluate the effects of a mixture of eugenol (14%), thymol (1%) and malate (85%) on growth performance, beef quality and liver function in Hanwoo finishing steers fed a high-concentrate diet. A feeding trial was conducted for 7 months in National Agricultural Cooperative Federation farm located in Anseong, Korea. Steers were assigned randomly to one of three treatments: control (without additive supplementation), treatment 1 (0.05% additive of concentrate), treatment 2 (0.1% additive of concentrate). The results of this study showed that initial and final BW averaged 564 and 755 kg, respectively, and BW gain was significantly higher (P<0.05) for steers fed the additive mixture than for those fed no mixture (0.78 and 0.79 vs. 0.69 kg/d, respectively). Serum aspartate aminotransferase in the T2 treatment was decreased during the 24 to 31 months of age. Although supplementation of additives resulted in no substantial effect on carcass characteristics, it had a potential effect to improve feed efficiency and AST concentration in Hanwoo finishing steers fed a high-concentrate diet. In conclusion, a mixture of eugenol, thymol and malate has shown promise in improving feed efficiency and liver function in the finishing phase of Hanwoo steers.

• Journal of Veterinary Clinics
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• v.30 no.2
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• pp.142-145
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• 2013

Equine motor neuron disease (EMND) is a spontaneous neurologic disorder of horses, which results from the degeneration of motor neurons in the spinal cord and brain stem. An 8-year-old Jeju pony gelding presented with weight loss, muscle tremors, frequent recumbence, low head carriage, sweating, and standing with four limbs close together. The gelding has been on the same stable and limited access to pasture for several years. The gelding has been fed with dried hays and commercial concentrated feeds. Laboratory test revealed very low serum vitamin E level (0.14 ${\mu}g/mL$; reference range > 1.5 ${\mu}g/mL$), mildly elevated creatine kinase (402 IU/L; reference range 119-287 IU/L) and aspartate aminotransferase (876 IU/L; reference range 226-336 IU/L). Oral glucose absorption test showed decreased glucose absorption. Histopathologic examination using a biopsy specimen from sacrocaudalis dorsalis medialis muscle revealed atrophic and hypertrophic muscle fiber, centralization of nucleus, degenerating and necrotic muscle fibers. Taken together, the gelding was diagnosed as EMND. After oral vitamin E administrated for 5 weeks, the gelding showed normally improved stance, decreased periods of recumbency, improved head carriage and weight gain except consistent tremors. This is the first report that successfully treated EMND case occurred in a Jeju pony in Korea.

• Journal of the Korean Society of Food Science and Nutrition
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• v.35 no.7
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• pp.828-834
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• 2006

We investigated whether two-kinds of mixture (NHDT-1 and NHDT-2) mainly composed of Hovenia dulcis Thunb had beneficial actions for alcohol and acetaldehyde degradation in acute alcohol treatment and liver protection from fatty liver induced by chronic alcohol administration. In acute alcohol degradation experiment, serum alcohol and acetaldehyde concentrations exhibited lower 1, 3 and 5 hours after taking 3 g ethanol per kg body weight in NHDT-1 treated rats, but not NHDT-2 including ginseng. On the contrast to the acute effect on alcohol degradation, the long-term alcohol administration revealed that NHDT-2, not NHDT-1, protected the increase in serum concentration of aspartate aminotransferase, alanine aminotrasferase and ${\gamma}-triglyceride$ metabolism similar to the rats not consuming alcohol, leading to decreased triglyceride accumulation in blood and liver. In liver morphological study, NHDT-1 preserved the regular hepatocyte morphology, decreased fat accumulation and reduced sinusoidal leukocyte infiltration in hepatocytes. In conclusion, NHDT-1 plays an important role in alcohol and acetaldehyde degradation without protecting liver damage while NHDT-2 works as hepatocyte protector from alcohol mediated damage.

• The Journal of Korean Obstetrics and Gynecology
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• v.27 no.1
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• pp.41-64
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• 2014

Objectives: This study was to evaluate the effect of Jaeumkanghwa-tang (JEKHT) on the propylthiouracil (PTU)-induced rat hypothyroidism. Methods: Six groups, each of 8 rats per group were used in the present study - intact vehicle control, PTU control, Levothyroxine ($LT_4$), JEKHT 500, 250 and 125 mg/kg treated groups. JEKHT were administered once a day for 42 days as an oral dose of 500, 250 and 125 mg/kg, and hypothyroidism was induced by daily subcutaneous treatment of PTU 10 mg/kg for 28 days. The changes on the body and organ weight, serum hormone and lipid profiles, liver and testis antioxidant defense factors were observed with histopathology of organs. Results were compared with $LT_4$ 0.5 mg/kg intraperitoneally treated rats in this experiment. Results: PTU treatment, marked decrease of body weight, increases of thyroid weight, decreases of liver, testis, epididymis and prostate weights, decreases of serum Tri-iodothyronine ($T_3$), and Thyroxine ($T_4$) level with increase of serum Thyroid-stimulating hormone (TSH) level, decreases of serum testosterone and dihydrotestosterone (DHT) level with increases of serum Follicular stimulating hormone (FSH) level, increases of serum High density lipoprotein (HDL), decrease of triglyceride content, increase of serum Aspartate aminotransferase (AST) level, decreases of liver and testis antioxidant defense factors were observed. In addition, marked hyperplasia of follicular cells with decreases of follicular colloid contents and diameters was additionally demonstrated with the decrease of hepatocyte numbers per unit area due to hypertrophy of hepatocytes related to lipid droplet depositions, increase of a/oligospermatic epididymal tubules with epididymal atrophic changes, seminiferous tubular atrophy with decrease of stage I~II seminiferous tubules in testis, prostate tubular atrophic changes at histopathological inspections. However, these PTU induced hypothyroidism and related hepatic and male reproductive organ damages were favorably and dose-dependently inhibited by treatment of JEKHT 500, 250 and 125 mg/kg, and JEKHT also effectively regulated the PTU-induced abnormal antioxidant defense factor changes in the both liver and testis. Conclusions: JEKHT 500, 250 and 125 mg/kg dose-dependently inhibited PTU-induced hypothyroidism and related liver and male reproductive organ damages in rats.

• The Korean Journal of Pharmacology
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• v.32 no.3
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• pp.407-416
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• 1996

The reactive intermediates formed during the metabolism of therapeutic agents, toxicants and carcinogens by cytochromes P450 are frequently capable of covalently binding to tissue macromolecules and causing tissue damage. It has been shown that YH439, a congener of malotilate, is effective in suppressing hepatic P450 2E1 expression. The present study was designed to further establish the mechanistic basis of YH439 protection against toxicant by assessing its effects against chemical-mediated potentiated hepatotoxicity. Retinoyl palmitate (Vit-A) pretreatment of rats for 7 days substantially enhanced carbon tetrachloride hepatotoxicity, as supported by an ${\sim}5-fold$ increase in serum alanine aminotransferase (ALT) activity, as compared to $CCl_4$ treatment alone. The elevation of ALT activity due to Vit-A was completely blocked by the treatment of $GdCl_3$ a selective inhibitor of Kupffer cell activity. Concomitant pretreatment of rats with both YH439 and Vit-A resulted in a 94% decrease in Vit-A-potentiated $CCl_4$ hepatotoxicity. YH439 was also effective against propyl sulfide-potentiated $CCl_4-induced$ hepatotoxicity. Whereas propyl sulfide (50 mg/kg, 7d) enhanced $CCl_4-induced$ hepatotoxicity by >5-fold, relative to $CCl_4$ treatment alone, concomitant treatment of animals with both propyl sulfide and YH439 at the doses of 100 and 200 mg/kg prevented propyl sulfide-potentiated $CCl_4$ hepatotoxicity by 35% and 90%, respectively. Allyl sulfide, a suppressant of hepatic P450 2E1 expression, completely blocked the propyl sulfide-enhanced hepatotoxicity, indicating that propyl sulfide potentiation of $CCl_4$ hepatotoxicity was highly associated with the expression of P450 2E1 and that YH439 blocked the propyl sulfide-enhanced hepatotoxicity through modulation of P450 2E1 levels. Propyl sulfide- and $CCl_4-induced$ stimulation of lipid peroxidation was also suppressed by YH439 in a dose-related manner, as supported by decreases in malonedialdehyde production. The role of P450 2E1 induction in the potentiation of $CCl_4$ toxicity and the effects of YH439 were further evaluated using pyridine as a P450 2E1 inducer. Pyridine pretreatment substantially enhanced the $CCl_4$ hepatotoicity by 23-fold, relative to $CCl_4$ alone. YH439, however, failed to reduce the pyridine-potentiated toxicity, suggesting that the other form(s) of cytochroms P450 inducible by pyridine, but not suppressible by YH439 treatment, may play a role in potentiating $CCl_4-induced$ hepatotoxicity. YH439 was capable of blocking cadmium chloride-induced liver toxicity in mice. These results demonstrated that YH439 efficiently blocks Vit-A-enhanced hepatotoxiciy through Kupffer cell inactivation and that the suppression of P450 2E1 expression by YH439 is highly associated with blocking of propyl sulfide-mediated hepatotoxicity.

• Journal of the Korean Society of Food Science and Nutrition
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• v.44 no.5
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• pp.657-663
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• 2015

Ionizing radiation induces cell damage through formation of reactive oxygen species. The present study was designed to evaluate the protective effects of post-treatment with hesperetin against ${\gamma}$-irradiation-induced cellular damage and oxidative stress in BALB/c mice. Healthy female BALB/c mice were exposed to ${\gamma}$-irradiation and administered hesperetin (25 mg/kg and 50 mg/kg, b.w., orally) for 7 days after 6 Gy of ${\gamma}$-irradiation. Exposure to ${\gamma}$-irradiation resulted in hematopoietic system damage manifested as decreases in spleen indexes and WBC count. In addition, hepatocellular damage characterized by increased levels of aspartate aminoransferase (AST) and alanine aminotransferase (ALT) in plasma. However, post-irradiation treatment with hesperetin provided significant protection against hematopoietic system damage and decreased AST and ALT levels in plasma. The results indicate that ${\gamma}$-irradiation induced increases in lipid peroxidation and xanthine oxidase (XO) as well as decreases in antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase) and glutathione (GSH) in the liver. These effects were also attenuated by post-treatment with hesperetin, which decreased lipid peroxidation and XO as well as increased antioxidant enzymes and GSH. These results show that post-treatment with hesperetin offers protection against ${\gamma}$-irradiation-induced tissue damage and oxidative stress and can be developed as an effective radioprotector during radiotherapy.