• Archives of Pharmacal Research
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• 제21권5호
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• pp.508-513
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• 1998

The hepatoprotective effect of DA-9601, a quality-controlled extract of artemisisa asiatica, on liver damage induced by acetaminophen (APAP) and carbon tetrachloride ($CCI_{4}$) was investigated by means of serum-biochemical, hepatic-biochemical, and histopathological examinations. Doses of Da-9601 (10, 30, or 100 mg/kg) were administered intragastrically to each rat on three consecutive days i.e. 48 h, 24 h and 2 h before a single administration of APAP (640 mg/kg, i.p.) or $CCI_{4}$ (2 ml/kg, p.o.). Four h and 24 h after hepatotoxin treatment, the animals were sacrificed for evaluation of liver damage. Pretreatment of Da-9601 reduced the elevation of serum ALT, AST. LDH and histopathological changes such as centrilobular necrosis, vacuolar degeneration and inflammatory cell infiltration dose-dependently. Da-9601 also prevented APAP- and $CCI_{4}$-induced hepatic glutathione (GSH) depletion and $CCI_{4}$-induced increase of hepatic malondialdehyde (MDA), a parameter of lipid peroxidation, in a chemically induced liver injury by complex mechanisms which involve prevention of lipid peroxidation and preservation of hepatic GSH.

• 동의생리병리학회지
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• 제24권3호
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• pp.439-445
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• 2010

Pretreatment with Taraxacum Mongolicum H(TMH) prior to the administration of on $CCl_4$ significantly prevented the increased serum enzymatic activity of aminotransferase(ALT, AST), gamma-glutamyl transpeptidase(GGT) and bilirubin concentration in dose-dependent manner. In addition, pretreatment with TMH also significantly restored the elevation of hepatic malondialdehyde formation and the depletion of reduced glutathione content in the liver $CCl_4$-intoxicated rats. The restoration of microsomal aniline hydroxylase and aminopyrine N-demethylase activities indicated the improvement in functional status of endoplasmic reticulum. $CCl_4$-induced hepatotoxicity was also essentially prevented, as indicated by a liver histopathologic study. TMH showed antioxidant effects in $FeCl_2$-ascorbate-induced lipid peroxidation in rat liver homogenate and in superoxide radical scavenging activity. Our results suggest that the protective effect of TMH against $CCl_4$-induced hepatotoxicity possibly involve mechanisms related to its ability to block p450-mediated $CCl_4$ bioactivation and free radical scavenging effects.

• 약학회지
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• 제42권6호
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• pp.598-606
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• 1998

The liver expresses a considerable amount of nitric oxide (NO) upon induction with cytokines or/and endotoxin. The NO synthesized by inducible NO synthase (NOS) of the liver see ms to play a role in various hepatic physiological processes. Here we investigate the effects of NO on acetaminophen (AA)-induced liver injury. The treatment of S-nitros-N-acetyl penicillamine (SNAP, exogenous NO donor) at the dose of 0.1mM decreased AA-induced hepatotoxicity suggesting the possibility of NO to play a role in protection from the hepatotoxicity induced by AA. On the other hand, the excessive NO produced by NO donor (SNAP: 0.5, 2.5, 6.25mM) has been shown to cause a concentration dependent hepatotoxicity, and such damages was decreased by Superoxide and increased by superoxide dismutase, indicating that the hepatotoxicity induced by excessive NO depends on balancing between NO and superoxide. Taken together, the results indicate that NO has biphasic effects on hepatotoxicity.

• Environmental Analysis Health and Toxicology
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• 제11권1_2호
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• pp.41-47
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• 1996

1, 2, 4-Trichlorobenzene (1, 2, 4-TCB) is used as a dye carrier, as an intermediate in the synthesis of herbicides, as a flame retardant, and for other purpose. After a single oral administration of 1, 2, 4-TCB (200 mg/kg, 400 mg/kg) in rats, toxic effects were studied by means of serum biochemical and heatological analysis, and liver calcium concentration. Administration of 1, 2, 4-TCB resulted in dose-dependent liver and kidney damage as estimated by increased serum alanine aminotransferase (ALT) activities, liver calcium concentration and blood urea nitrogen (BUN). Pretreatment with DL-buthionine sulfoximine (BSO, 2 mmol/kg, i.p. ) considerably decreased liver glutathione concentration, which was accompanied by markedly elevated serum ALT activites. It is well-known that toxicity of halogenated benzene such as bromobenzene, 1, 4-dichlorobenzene is increased by pretreatment of henobarbital (PB), and protected by pretreatment of cytochrome P450 inhibitor including metyrapone (MP). However, there was no obvious alterations in toxicity of 1, 2, 4-TCB by pretreatment of phenobarbital or metyrapone. In comparison with control group, treatment groups exhibited significant changes in some parameters of hematological analysis but all hematological values remined within normal ranges.

• 한국식품조리과학회지
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• 제13권1호
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• pp.23-29
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• 1997

The hypoglycemic effect of fractions of methanol extract of Cassia tora was investigated in diabetic rats. Sprague-Dawley male rats weighing 180∼230 g were divided into 6 groups. Diabetes was induced in the male rats by intravenous injection of streptozotocin at a dose of 45 mg/kg dissolved in citrate buffer (pH 4.5). The diabetic animals then had plasma glucose concentration of above 300 mg/㎗. Fractions of methanol extract of Cassia tora were administered orally into the diabetic rats for 14 days after streptozotocin injection. The food intake and body weight gain were monitored and plasma levels of glucose, triglyceride, free fatty acid, HDL-cholesterol, cholesterol and ALT activity were determined. Levels of glycogen, cholesterol and triglyceride in liver were analysed. Weights of liver and kidney were lighter in all the fraction-administered groups than streptozotocin-control group. Plasma glucose level was significantly decreased by the administration of butanol fraction at 14 days. Plasma triglyceride levels were lower in chloroform, butanol and H$_2$O fraction-administered groups compared to streptozotocin-control group. Plasma cholesterol and HDL-cholesterol levels were not significantly different in all groups. Administrations of each of the four fractions have decreased plasma free fatty acid level, ALT activity and liver triglyceride levels in the diabetic rats. Liver glycogen levels in chloroform, butanol and H$_2$O fraction-administered groups were higher than streptozotocin-control group. It is suggested from the results that butanol fraction of methanol extract of Cassia tora may contain the antihyperglycemic compounds.

• 고려인삼학회:학술대회논문집
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• 고려인삼학회 1990년도 Proceedings of International Symposium on Korean Ginseng, 1990, Seoul, Korea
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• pp.58-64
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• 1990

The effects of ginseng saponins, G-Rbl and G-Rc on the rat liver LDH A-gene transcnptional activity was investigated during pro-replicative phase of rat liver after partial hepatectomy. Changes in LDH A-mRNA levels in regenerating rat liver after intraperitoneal administrations of G-Rbl of G-Rc were tested by slot blot hybridization methods. The results showed that G-Rbl (1 mg/100g B.W) and G-Rc (1 ma/100g B.W) caused marked increases of LDH A-mRNA contents by respectively 1.9- and 1.5-fold in rat liver at 5·hours after partial hepatectomy. Dose dependent effect of G-Rbl and G-Rc (1-25 mg/100g B.W) on the LDH A-mRNA levels on regenerating rat liver were also analyzed. The maximal in- creases of liver LDH A-mRNA levels were observed with the doses of 1 mg for G-Rbl and 5 mg for G-Rc However, when the administration doses of G-Kbl and G-Rc were increased to 20 mg, G-Rbl caused a marked decrease of LDH A-mRNA level to 61% of those in sham-operated rat liver In contrast, G-Rc slightly decreased the liver LDH A-mRNA contents by 30% as compared to those of the maximum value but still maintained 22% higher LDH A-mRNA levels then those of sham-operated rate liver. On the basis of these experimental results, we conclude that ginseng saponin, G-Rb 1 and G·Rc have stimulatory effect at the lower concentration (1 mg/100g B.W) and inhibitory effect at the higher concentration (20 moi loos 5.W) on the LDH A-gene transcription during regeneration of rat liver, Additionally we also investigated the stimulatory effects of ginsenosides on the protein and DNA synthetic activities in hepatocyte primary cell cultures isolated from regenerating rat liver. Both of G·Rc and -Re increased the synthetic rates of hepatocytes proteins and DNA at the administration doses of 50 ug and 100 ug/3 ml/dish respectively representing 1.3-1.6 fold increases. From these results we postulate that G-Rc and -Re may have a mitogen enhancer activity for the hepatocyte proliferation during rat liver regeneration period. Keywords Inductive effects of ginsenosides, G-Rb, -Rc, and -Re, rat LDH A-gene transcription, the sin thetic rate of proteins and DNA in regeneration rat liver.

• Toxicological Research
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• 제23권4호
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• pp.391-403
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• 2007

The study was conducted to assess the repeated dose and reproduction and developmental toxicities of acetanilide, an intermediate for drug production, as a part of OECD Screening Information Data Set (SIDS) program. The test agent was administered by gavage at dose levels of 0, 22, 67, 200 and 600 mg/kg to Sprague-Dawley rats (12/group/sex) during pre-mating and mating period for males(up to 30 days) and females and pregnancy and early lactation period for females (up to 39-50 days). At 22 mg/kg, decreases in HGB, HCT (males) and MCHC (females), hyperplasia of spleen red pulp, hyperplasia of femur bone marrow (both sexes) were observed. At 67 mg/kg, salivation (males), reduced food consumption (both sexes), decreases in RBC, HGB, HCT and MCHC (males), increases in MCV (males) and spleen weight (males), hyperplasia of spleen red pulp and femur bone marrow (both sexes) were observed. At 200 mg/kg, decreases in locomotor activity and salivation (both sexes), reduced food consumption (both sexes), decreases in RBC, HGB, HCT and increases in MCV, MCH, BUN, T-BIL (males), enlargement of spleen (both sexes), increased weight of spleen (males), hyperplasia of spleen red pulp and femur bone marrow and extramedullary hematopoiesis of liver (both sexes), atrophy of thymus and corpus luteum hyperplasia of ovary (females) were observed. At 600 mg/kg, decreases in locomotor activity, cyanosis (both sexes), reddish tear, and salivation (males), mortality (4 out of 12 females), decreased body weight (females), reduced food consumption (both sexes), decreases in RBC, HGB, HCT and MCHC and increases in WBC, MCV, MCH, reticulocyte, neutrophil, lymphocyte, monocyte, AST, ALT, BUN, T-BIL, ALB, Ca and A/G ratio (males), enlargement of spleen, increased weights of spleen (both sexes), liver (males), kidney and ovary, decreased weights of thymus (females), hyperplasia of spleen red pulp, hyperplasia of femur bone marrow and extramedullary hematopoiesis of liver (both sexes), and atrophy of thymus and corpus luteum hyperplasia of ovary (females) were observed. Regarding the reproduction and development toxicities, there were no treatment-related changes in precoital time, mating index, fertility index and pregnancy index at all doses tested. At 22 and 67 mg/kg, there were no adverse effects on all the parameters observed. At 200 mg/ kg, decreased body weight of pups (day 4 p.p.) were observed. At 600 mg/kg, decreased body weight of pups (day 0 and 4 p.p.) and viability index (day 4 p.p.), increased incidence of newborns dead or with abnormal clinical signs were observed. The results suggest that the NOAELs for general toxicity are < 22 mg/kg, LOAELs are 22 mg/kg and the NOAELs for reproductive toxicity are 67 mg/kg.

• Clinical and Experimental Reproductive Medicine
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• 제14권1호
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• pp.61-70
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• 1987

This study was carried out to investigate the effects of the antiestrogens, LY-117018 and tamoxifen on reproductive organ of ovariectomized immature rats and also to elucidate the mechanism of action of said compounds by bioassay. Each of LY-117018, tamoxifen and estradiol-17${\beta}$ was administered to ovariectomized immature rats at various dose levels. Forty hours after drug administration, tested rats were sacrificed and uterine wet weight, DNA and RNA contents in uterine and liver tissues were investigated. At the same time, uterine wet weight was also investigated with some other rats treated with 125${\mu}g$ of LY-117018 together with increasing doses of tamoxifen. Ovariectomized immature rats given 25${\mu}g$ single dose of each drug were sacrificed on Day 1, 2, 3, 4, and 5 after drug administration and uterine was weighed to estimate the duration of action of LY-117018 and tamoxifen. The results were summarized as follows: 1. The administration of LY-117018 or tamoxifen to ovariectomized rats increased uterine wet weight and DNA and RNA contents in uterine tissues with more increase in tamoxifen groups, but significant differences between groups treated at dose levels of 5${\beta}$ or more of both drugs were observed. Estradiol-17${\beta}$ groups showed significant increases in each group(P<0.01). 2. The administration of LY-117018 or tamoxifen to each group significantly increased DNA and RNA contents in liver tissues with more increase in tamoxifen groups. Estradiol-17${\beta}$ groups showed no significant differences between treatment groups of 5${\beta}$ or more. 3. Treatment with 125${\beta}$ of LY-117018 together with various doses of tamoxifen resulted in more increase of uterine wet weight than treatment with a single dose of LY-117018 or tamoxifen. 4. Treatment with 0.2${\beta}$ of LY-117018 or tamoxifen in ovariectomized rats decreased uterine wet weight,DNA and RNA contents in liver and uterine tissues compared with ovariectomized control. 5. The duration of effective action of LY-1l7018 and tamoxifen was 4 days or more. 6. There was significant difference(P<0.001) in uterine wet weight between Day 9after ovariectomy (two days after LY-117018 or tamoxifen treatment) and Day 10(63.7${\pm}$3.5mg, 39.2${\pm}$9.9mg, respectively).

• 대한방사선치료학회지
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• 제13권1호
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• pp.38-46
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• 2001

Purpose : The aim of this study is to investigate the effect of tissue inhomogeneities when appling to contrast medium among Homogeneous, Batho and ETAR dose calculation method in RTP system. Method and Material : We made customized heterogeneous phantom it filled with water or contrast medium slab. Phantom scan data have taken PQ 5000 (CT scanner, Marconi, USA) and then dose was calculated in 3D RTP (AcQ-Plan, Marconi, USA) depends on dose calculation algorithm (Homogeneous, Batho, ETAR). The dose comparisons were described in terms of 2D isodose distribution, percent depth dose data, effective path length and monitor unit. Also dose distributions were calculated with homogeneous and inhomogeneous correction algorithm, Batho and ETAR, in each patients with different clinical sites. Results : Result indicated that Batho and ETAR method gave rise to percent depth dose deviation $1.5{\sim}2.7\%,\;2.3{\sim}3.5\%$ (6MV, field size $10{\times}10cm^2$) in each status with and without contrast medium. Also show that effective path lengths were more increase in contrast status (23.14 cm) than Non-contrast (22.07 cm) about $4.9\%$ or 10.7 mm (In case Hounsfield Unit 270) and these results were similary showned in each patient with different clinical site that was lung. prostate, liver and brain region. Concliusion : In conclusion we shown that the use of inhomogeneity correction algorithm for dose calculation in status of injected contrast medium can not represent exact dose at GTV region. These results mean that patients will be more irradiated photon beam during radiation therapy.

• 대한의생명과학회지
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• 제25권1호
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• pp.83-91
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• 2019

This study was undertaken to investigate the therapeutic effect of Angelica acutiloba on allergic dermatitis, which Angelica acutiloba is traditionally known to have antiinflammatory effects. Sprague-Dawley (SD) rats were divided into five groups: normal control group, experimental allergic dermatitis group (vehicle group), low dose of Angelica acutiloba extract (low-dose group), high dose of Angelica acutiloba extract (high-dose group), and antihistamine treated group with experimental dermatitis (antihistamine group). Total leukocyte, neutrophil, lymphocyte, monocyte and eosinophil counts were significantly higher in the vehicle group than in the control group, but these variables were significantly lower in the low- and high-dose groups than in the vehicle group. The platelet/lymphocyte ratio in the red blood cell index was significantly lower in the low- and high-dose groups than in the vehicle group. Low and high doses of the Angelica acutiloba extract did not have toxic effects on liver and kidney. Serum NO, iNOS and levels were highest in the vehicle group but significantly lower in the low- and high-dose groups, especially in the high-dose group. The results of this study suggested that the Angelica acutiloba extract had the effect of alleviating or treating the experimental allergic dermatitis, and it was concluded that the high dose was more effective.