• Toxicological Research
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• v.25 no.2
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• pp.85-92
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• 2009

4,4'-Methylenedianiline (MDA) is an aromatic amine that is widely used in the industrial synthetic process. Genotoxic MDA forms DNA adducts in the liver and is known to induce liver damage in human and rats. To elucidate the molecular mechanisms associated with MDA-induced hepatotoxicity, we have identified genes differentially expressed by microarray approach. BALB/c male mice were treated once daily with MDA (20 mg/kg) up to 7 days via intraperitoneal injection (i.p.) and hepatic damages were revealed by histopathological observation and elevation of serum marker enzymes such as AST, ALT, ALP, cholesterol, DBIL, and TBIL. Microarray analysis showed that 952 genes were differentially expressed in the liver of MDA-treated mice and their biological functions and canonical pathways were further analyzed using Ingenuity Pathways Analysis (IPA). Toxicological functional analysis showed that genes related to hepatotoxicity such hyperplasia/hyperproliferation (Timp1), necrosis/cell death (Cd14, Mt1f, Timp1, and Pmaip1), hemorrhaging (Mt1f), cholestasis (Akr1c3, Hpx, and Slc10a2), and inflammation (Cd14 and Hpx) were differentially expressed in MDA-treated group. This gene expression profiling should be useful for elucidating the genetic events associated with aromatic amine-induced hepatotoxicity and for discovering the potential biomarkers for hepatotoxicity.

• YAKHAK HOEJI
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• v.42 no.6
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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.

• Journal of Ginseng Research
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• v.22 no.1
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• pp.1-10
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• 1998

In the present study, to determine whether the antioxidative components of Korean red ginseng protect against radiation damage and the possible relationship among the radioprotective effects and antioxidant actions, the effects of total saponin (200 mg/kg, ip) and lipophilic fraction (200 mg/kg, oral) preferment of mice on the survival ratio, major antioxidant enzymes (SOD, catalase and glutathione peroxidase) activities, glutathione levels and lipid peroxidation in the liver were exiled for 2 weeks after whole ${\gamma}$-body ${\gamma}$-irradiation (6.5 Gy). The 30-day survival ratio increased from 10% to 57% and 40% for mice treated with total saponin and lipophilic fraction, respectively. On day 14 after ${\gamma}$-irradiation, the ginseng total saponin pretreatment produced a slight increase of antioxidant enzymes activities and significantly Increased reduced glutathione (GSH) contents (p<0.05) in the liver compared with non-treated group. Pretreatment with ginseng total saponin significantly deceased GSSG/total GSH ratio (p<0.05) without change of GSSG in the liver and inhibited the radiation-induced incense in the hepatic malondialdehyde levels. (p<0.05) In these results, GSH plays an important role in the liver in several detoxifications and the reduction of lipid peroxides. Thus, it appears that total saponin of red ginseng exerts its radioprotective effect by accelerating the production of endogenous antioxidants, such as glutathione from radiation induced damages and thereby oxygen free radicals.

• Applied Biological Chemistry
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• v.48 no.4
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• pp.358-363
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• 2005

Effects on the feeds of streptozotocin-induced diabetic rats with a giant embryonic rice on lipid peroxides level and antioxidative enzyme activites in plasma and liver tissues were investigated. Along with the experimental periods, all animals in diabetic groups had a lower increase rate in body weight than the normal control group. A giant embryonic rice-fed group showed a inhibition in the decrease of body weight, and a increase in feed intake compared to the normal control group. The organ weights of the diabetic control group were heavier than those of the normal control while rice-fed groups including the giant embryonic rice-fed group were found to have lower organ weights, and its blood sugar level was found to be lower than those of the normal group. Lipid peroxides of the giant embryonic rice-fed animals showed a lower lipid peroxidation values compared to that of the diabetic control group. Plasma vitamin A and E concentrations of the diabetic control group were significantly decreased compared to the normal control while those of the giant embryonic rice-fed group were found to be significantly higher than those of the diabetic control. Of the hepatic antioxidative enzymes, SOD activity of the giant embryonic rice-fed group was higher than that of the diabetic control group. Taken these together, low lipid peroxidation values and, in contrast, high antioxidative enzyme activities were thought to be a cause for decreasing hepatic oxidative damages.

• Asian-Australasian Journal of Animal Sciences
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• v.24 no.10
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• pp.1425-1434
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• 2011

This experiment was designed to evaluate the effects of the processing method of common vetch seed (CVS) (Vicia sativa) on laying performance, egg quality, metabolic parameters and liver histopatology during the peak production period in hens. Lohman layers, 46 wk of age in 6 replicate cages each containing 4 hens, were allocated randomly to one of four dietary treatments. Diets were control (C) diet containing no common vetch and experimental diets containing 25% raw common vetch (RCV), 25% soaked in water for 72 h with exchange of water every 24 h (SCV) and 25% soaked&boiled at $100^{\circ}C$ for 30 minute common vetch (SBCV). Inclusion of RCV into the diet deteriorated all laying performance variables. SCV did not alleviate the adverse effect of raw common vetch on feed intake, egg weight, feed conversion, final weight and weight change. SCV partially alleviated egg production (p<0.001). SBCV diminished the adverse effect on feed intake, egg weight, feed conversion, final weight and weight change compared to raw vicia sativa (p<0.001). No significant difference was detected between SBCV and the control group in terms of egg production, feed conversion, final weight and weight change. Regardless of the processing method, all the common vetch groups had lower shell strength compared to the control group. Haugh units did differ between all groups (p<0.001). Inclusion of RCV and SCV into the basal diet decreased triglyceride, cholesterol, total protein and serum glucose concentrations (p<0.001). Hovewer, inclusion of SBCV into the basal diet increased these parameters. Liver samples were stained with Hematoxylin and eosin (HE) and evaluated by light microscopy. A biopsy of native liver tissue was used as a control. No histopathologic finding was present in the control group. Raw V. sativa compared with the control caused lipid accumulations in hepatocytes, severe congestion of hepatic blood vessels, inflammation, increased numbers of Kupffer cells and sinusoidal dilatations. Whereas, the livers from groups given treated V. sativa showed only different degrees of sinusoidal dilatations. Findings from the present study point out the risk of increased hepatic damage due to use of raw Vicia sativa. Increasing treatment of V. sativa lead to a decrease of liver damages. Inclusion of raw and soaked vetch seeds in rations affected adversely all parameters examined in laying hens. But alleviation was observed when soaked and boiled vetch seeds (SBCV) were fed. The results of these experiments indicated that soaked&boiled Vicia sativa seeds may safely be used at a 25% level in rations of laying hens.

• The Korea Journal of Herbology
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• v.31 no.1
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• pp.33-40
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• 2016

Objectives : Liver is one of the largest organs in the human, and has a function of detoxification and energy sensing to prevent severe disease. Paeoniae radix has been used to treat a variety of liver diseases such as hepatitis and chronic hepatic failure. Although P. radix has been used as an medicinal herb for a long time, the effects of P. radix on severe oxidative stress and its action mechanism on the liver was not clearly verified.Methods : This study investigated the protective effects of P. radix extract (PRE), and the underlying mechanism of its action in the liver. tert-butyl hydroperoxide (t-BHP) and carbon tetrachlroride (CCl₄) were used to induce oxidative stress in the HepG2 hepatocyte cell line and Sprague-Dawley rats, respectively.Results : t-BHP significantly induced cell death and ROS production in HepG2 cell, as indicated by MTT and FACS analysis. However, pretreatment of PRE inhibited a decrease in cell viability and H₂O₂ production in the HepG2 cells. PRE also blocked the ability of t-BHP to damage in mitochondrial membrane transition. More importantly, PRE induced Nrf2 activation and antioxidant Phase II enzyme, which may have a role in the effects of PRE. In mice, PRE inhibited the liver damage induced by CCl₄.Conclusions : PRE inhibited oxidative stress and hepatic damages as mediated with Nrf2 activation. This study unveil, in part, the effect and mechanism of old medicinal herb, P. radix.

• Korean Journal of Food Science and Technology
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• v.34 no.4
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• pp.684-687
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• 2002

Water and methanol extracts of cricket were examined for their liver protective effects against $CCl_4-intoxication$ in ICR-mice. Serum transaminases (S-GOT and S-GPT), lactate dehydrogense (LDH) and glutathione-S-transferase (GST) activities and TBARS (Thiobarbiturate-reactive substances) content were measured for evaluation of liver protective effects. The activities of GOT, GPT, LDH and hepatic content of lipid peroxide after $CCl_4-treatment$ were higher than normal control but those levels decreased th 74, 50, 101 and 40%, respectively, by the treatment of cricket methanol extract. The anti-fatigue effects of water and methanol extracts investigated by an acute weight-loaded forced swimming test showed significantly prolonged swimming time in the mice administered cricket extracts. These results suggest us that water/alcohol extract of G. bimaculatus may be used as a liver protective food.

• Nutritional Sciences
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• v.9 no.4
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• pp.267-272
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• 2006

The effect of methanol extract from Agaricus blazei Murill on the hepatotoxicity was investigated $CCl_4$ is one of the oldest and most widely used toxins for the induction of hepatic damages and fibrosis in experimental animals. In this study, male Sprague-Dawley(SD) rats were randomly divided into 6 groups of the control(C), $CCl_4(T),\;CCl_4$ and high fat group(TL) with matching sub-groups of Agaricus blazei Murill extract-fed groups of CA, TA and TLA. Methanol extracts of Agaricus blazei Murill were fed 50 mg/kg B.W daily via drinking water. A 1.2 mL of $CCl_4/kg$ body weight was administered by oral intubation twice a week for total of six times. The levels of total-cholesterol, TG, LDL and LDL-phospholipids were elevated by $CCl_4$ treatment as compared to the control(C). However, Agaricus blazei Murill methanol extract feeding in the group of TA and TLA significantly(p<0.05) decreased TG by 53.1 % and 17.9% compared to the internal control of T and TL, respectively. Triglyceride of TL was increased by 3.33 times(p<0.05) compared to the control(C) with $CCl_4$ and high fat administration from 3.78 mg/g to 12.60 mg/g liver. The extract(CA) also reduced kidney weight compared to the control(C). With the administration of high fat and $CCl_4$(TLA), the extract reduced the organ weight of both liver and kidney and further, significantly reduced TG, total cholesterol and GTP activity. Hepatoprotective effects of Agaricus blazei Murill on GOT, GPT, AP and LDH activities were enhanced by the extract feeding. Electronmicrograph showed that $CCl_4$ deteriorated the structure of cytoplasmic matrix with its uneven distribution. However, the extract reconstituted the damaged cytoplasm and stimulated mitochondriogenesis. The above results suggest that Agaricus blazei Murill may have a possible protective effect against chemically induced liver damage and further help to reduce the symptoms of fatty liver.

• YAKHAK HOEJI
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• v.30 no.5
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• pp.253-265
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• 1986

Among 230 species of herbal drugs screened, thirty one show the anthelmintic activities in vitro against Clonorchis sinensis, the chinese liver fluke. The active substances have been isolated and their structures identified. Some of the active substances and their derivatives have been synthesized, followed by anthelmintic activity tests. The extracts from the active drugs cause damages in organs of the adult worm in the hepatic duct of rabbit. Some fresh water fish, which function as bad hosts for the fluke, excrete defense substances against the cercaria of the fluke. The defense substances have been isolated from Cyprinus carpio and Cyprinus carpio nudus, followed by structural identification. The results are summarized as follows: l) The bark of Machilus thunbergii as well as the seed of Schizandra chinensis contain meso-dihydro-guaiaretic acid as the anthelmintic component. Among derivatives synthesized, 4-phenyl-1-((3, 4-dihydroxyphenyl)-, 4-phenyl-1-(3-hydroxy-4-methoxy phenyl)-and 4-phenyl-1-(4-hydroxy-3-methoxy phenyl)-2, 3-dimethyl butanes show considerable activities. Administration of the bark extract mainly damages the bladder of the adult worm. 2) The active substance from the roasted fruit of Prunus mume is 2-hydroxymethylfurfural. This substance is produced during the roasting process. Administration of the fruitextract causes a damage of the bladder of the adult worm. 3) The active substance from the root of Scutellaria baicalensis is 5.2'-dihydroxy-6, 7, 8, 6'-tetramethoxyflavone. 4) Beside alantolactone, a very strong anthelmintic component is contained in the root of Inula helenium. Administration of the root extract causes irreversible damage on the worm, affecting mainly the reproductive organs. 5) The cercaricidal substances from the epidermis of C. carpio and C. carpio nudus are ethyl linoleate and linoleic acid, respertively. 6) The cercaricidal substances from various kinds of fresh water fish have different $R_f$ values, implying that the defense substances are species-specific. Unexpectedly, the fish with good host function, for example Pseudorasbora parva, excrete the defense substances, too. The defense substances are possibly organ-specific in individual species; the organs essenstial for the existence of the species excrete the defense substances, allowing other parts to be invaded by the cercaria. 7) The cercaricidal fraction of Carassius carassius is detected only in the fish which have been collected during the summer time from May to September, Its secretion is not dependent on water temperature. Thus, it seems to be possible that the secretion of the defense substance would be stimulated through a contact between the fish and cercaria.

• 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.