• Archives of Pharmacal Research
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• v.26 no.9
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• pp.763-767
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• 2003

The differences in pharmacokinetic behavior and tissue distribution of verapamil and its enantiomers were investigated in rats. In high-performance liquid chromatographic method, an achiral ODS column (150 mm $\times$ 4.6 mm i.d.) with the mobile phase consisting of methanol-water (73:30, v/v) was used for the determination of the concentration for racemic verapamil, and a Chiralcel OJ column (250 mm$\times$4.6 mm i.d.) with the mixture of n-haxane-ethanol-triethylamine (85:15:0.2, v/v/v) as mobile phase was used to determine the concentrations of verapamil enantiomers. A fluorescence detector in the analytical system was set at excitation and emission wavelengths of 275 nm and 315 nm. The differences between enantiomers were apparent in the pharmacokinetics in rats. The area under the concentration-time curve (AUC) of S-(-) verapamil was higher than that of R-(+) verapamil. The half-distribution time ($T_{1/2(\alpha)}$) of S-(-) verapamil which distributing to tissue from blood was shorter than that of R-(+) verapamil, but the elimination half-time ($T_{1/2(\beta)}$) was longer in rat following oral administration of racemic verapamil. At 1.3 h after oral administration of racemic verapamil, however, there were no significant differences between enantiomers for the distributions in major tissues such as heart, cerebrum, cerebellum, liver, spleen and kidney.

• Korean Journal of Acupuncture
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• v.25 no.2
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• pp.211-224
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• 2008

Objectives : To investigate the effect of electro-acupuncture (EA) at GB34 on hepatotoxicity in $CCl_4$-intoxicated rats. Methods : Rats were injected with $CCl_4$ and treated with acupuncture or 2 Hz electro-acupuncture (EA) at left GB34 three times a week for 10 weeks. A non-acupoint in left gluteal area was selected as a sham point. To estimate the effects of EA on hepatotoxicity in rats, body weight, liver weight and liver index were measured, and biochemical assays for serum ALT, AST, ALP and total cholesterol, and hematological analysis for RBC, WBC, PLT, hemoglobin, lymphocytes, neutrophils and monocytes, and histology analysis of liver tissue were performed. Results : 1. Lymphocyte level in blood was significantly decreased by $CCl_4$-intoxication and significantly increased by acupuncture and 2 Hz EA at left GB34. 2. Neutrophill and monocyte level in blood was increased by $CCl_4$-intoxication and significantly reduced by acupuncture and 2 Hz EA at left GB34. 3. Acupuncture and 2 Hz EA at left GB34 significantly reduced serum ALT and AST which were increased by $CCl_4$-intoxication. 4. EA at GB34 significantly reduced serum ALT and AST as compared with EA at sham point in $CCl_4$-intoxicated rat. 5. No significant difference was found between the effects of acupuncture and that of 2 Hz EA on $CCl_4$-induced liver damage in rats. Conclusions : 2 Hz EA at GB34 has hepatoprotective effects on $CCl_4$-induced liver damage in rats and the point-specificity of GB34 may be involved in these effects.

• The Journal of Korean Medicine
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• v.33 no.2
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• pp.47-55
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• 2012

Objectives: This study aimed to investigate the preventive effect of red ginseng (RG) on 5-fluorouracil (5-FU)-induced side effects focusing on myelosuppression. Methods: Rats (n = 50) were divided into five groups, nave, control (ip, 5-FU injection of 150 mg/kg), and RG pre-treatment (po, 25, 50 and 100 mg/kg for 5 days before 5-FU injection). On the $7^{th}$ day after 5-FU injection, we evaluated the effects using peripheral hematological parameters, colony-forming assay, cytokine levels and histopathological finding. Results: The peripheral white blood cell and the differential count were dramatically suppressed by 5-FU, while RG (50 and 100 mg/kg) treatment significantly improved total white blood cell, neutrophil, lymphocyte and platelet counts. Also, RG (100 mg/kg) pre-treatment significantly increased the number of CFU-GM colony compared with the control group. RG pre-treatment also ameliorated the histopathological damage in bone marrow, spleen, stomach and small intestine tissue. Conclusions: These results demonstrate that Korean RG has preventive effects against 5-FU-induced myelotoxicity and gastrointestinal damage.

• The Korea Journal of Herbology
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• v.36 no.2
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• pp.31-42
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• 2021

Objectives : This study was undertaken to investigate the hepatoprotective effect of Spatholobi Caulis water extract (SC) to thioacetamide (TAA)-induced acute liver injury (ALI) in rats. Methods : The rats were injected intraperitoneally with TAA (200 mg/kg body weight) and orally administered SC (100 or 200 mg/kg b.w.) daily for 3 days. Liver biomarkers were assessed by serum glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), and ammonia levels. Malondialdehyde (MDA) was measured both serum and liver tissue. In addition, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, anti-oxidant, and inflammation-related proteins were investigated by western blot analysis. Histological examination further confirmed though hematoxylin and eosin stain. Results : The SC treatment reduced liver function markers like GOT and GPT and also remarkably decreased ammonia level. Moreover, the elevated MDA level in TAA-induced group was significantly reduced by SC treatment. NADPH oxidase expression associated with oxidative stress including NOX2, NOX4, and p47phox markedly inhibited by SC administration. SC treatment exerted anti-oxidant effect through the increase of anti-oxidant enzyme including superoxide dismutase (SOD), Catalase, and heme oxygenase-1 (HO-1). The protein expressions of inflammatory cytokines such as tumor necrosis factor-�� (TNF-��), IL-6, and IL-1�� induced by nuclear factor-kappa B (NF-��B) activation were modulated through blocking the phosphorylation of inhibitor of nuclear factor ��B�� (I��B)��. SC treatment also improved histological alterations. Conclusion : These findings suggested that SC administration may be a potential candidate for the prevention or treatment of ALI.

• Biomedical Science Letters
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• v.12 no.1
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• pp.23-27
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• 2006

The rate of metallothionein synthesis on cadmium-poisoned rats reflects the level of toxicity, and also it reduces the toxicity which is caused by the uptake of cadmium. Chlorella supplementation in the diets of the cadmium-poisoned rats decreased the concentration of cadmium in blood and urine compared with the control group. Although the liver and kidneys of rats are major target organs of cadmium and coherence of metallothionein and cadmium, no previous study has determined the correlation between the rate of metallothionein synthesis in the liver and kidneys of rats and dietary supplementation of chlorella with cadmium uptake. This study analyzed total metallothionein level on the tissue of the liver and kidneys, the concentration of cadmium bound to the metallothionein, and the total concentration of cadmium on the tissue of the liver and kidneys after dietary supplementation with 1%, 5%, and 10% dried chlorella and 40 ppm of cadmium to 46 male SD rats (mean weight: $150\pm20\;g$) for 4 weeks. According to the data analysis of the total rate of metallothionein synthesis in the liver and kidneys, the group of SD rats on the supplementation with 1% chlorella and 40 ppm of cadmium showed a rate of $93.2\pm8.9\;ng/g$, a significant decrease of 58.8% compared to that of the control group of SD rats on the supplementation with cadmium only, which showed a rate of $227.3\pm32.5 ng/g$ (P=0.0001). In contrast, no significant difference was observed through the changing of chlorella concentrations between 5% and 10% chlorella supplementation with cadmium. The group supplemented with 1% or greater chlorella levels represented a greater decrease in the total cadmium concentration of the kidney and liver tissues, the amount of total metallothionein synthesis, the amount of metallothionein with binding to cadmium, and the concentration of free cadmium without binding to metallothionein. Consequently, the supplementation of 1% and 5% chlorella was effective in reducing the synthesis of metallothionein for cadmium uptake, but increased the rate of binding of cadmium to metallothionein.

• Journal of Nutrition and Health
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• v.6 no.1
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• pp.15-29
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• 1973

Albio rats right after weaning, weighing $50{\sim}55g$, were divided into the control, high-carbohydrate-, high-lipid-, and high-protein-fed groups. and were fed for 12 weeks with the respective diets to observe the increase in body weights as well as changes in the chemical constituentes and enzyme activities in the liver tissue, with the following results. (1) There was little difference in the rate of increase in the body weights among the groups, showing normal growth, except the high-protein-fed group which showed decrease in rate of body weight increase from the 7th week after feeding. (2) The liver weight was either increased after 12 weeks of feeding with the high-carbohydrate and high-Lipid diets, or showed no difference with the high-protein diet, as compared to the control weight. (3) The liver cytosol protein content was increased when fed with the high-protein diet, but decreased when fed with the high-carbohydrate and high lipid diets, as compared to the control content. (4) The triglyceride and cholesterol contents in the liver were decreased in the high-protein-fed group, but increased markedly in the high-carbohydrate- and high-lipid-fed groups as compared to the control values. (5) The hepatic glucokinase, G6PD, LDH, and fatty acid synthetase activities were increased in the high-carbohydrate and high-lipid-fed groups, and GOT and CPT activities were increased in the high-protein-fed group. From the above results. it was known that the high-carbohydrate and high-lipid diets stimulated the hepatic lipid metabolism, giving rise to lipogenesis, but the high- protein diet could prevent the lipogeuesis leading to the body weight increase.

• The Korean Journal of Physiology and Pharmacology
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• v.1 no.2
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• pp.151-159
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• 1997

In an attempt to investigate whether hemorrhage affects the gene expression of the renin-angioteusin system (RAS) components in the brain and peripheral angiotensin-generating tissues, changes in mRNA levels of the RAS components in response to hemorrhage were measured in conscious unrestrained rats. Wistar rats were bled at a rate of 3 ml/kg/min for 5 min, and then decapitated 7 h after hemorrhage. Levels of mRNA for renin, angiotensinogen and angiotensin $II-AT_1$ receptor subtypes ($AT_{1A}$ and $AT_{1B}$) were determined with the methods of northern blot and reverse transcriptase-polymerase chain reaction (RT-PCR). Hemorrhage produced a profound hypotension with tachycardia, but blood pressure and heart rate recovered close to the basal level at 7 h. Plasma and renal renin levels were significantly increased at 7 h. Hemorrhage induced rapid upregulation of gene expression of both $AT_{1A}$ and $AT_{1B}$ receptor subtypes in the brainstem and hypothalamus, downregulation of them in the adrenal gland and liver. However, renin mRNA level increased in the brainstem, decreased in the liver, but was not changed in the hypothalamus, kidney and adrenals after hemorrhage. Angiotensinogen mRNA level was not significantly changed in any of the tissue except a slight increase in the liver. The kidney and liver did not show any significant change in gene expression of the RAS components. These results suggest that gene expression of the RAS in central and peripheral tissues are, at least in part, under independent control and the local RAS in each organ plays specific physiologic role.

• Journal of the Korean Society of Food Science and Nutrition
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• v.30 no.3
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• pp.521-527
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• 2001

The effects of dietary restriction (DR) on antioxidant enzymes were studied in liver, lung and erythrocytes of diabetic rats. Experimental animals used Sprague-Dawley (SD; body weight 350$\pm$20g) male rats and Otsuka Long Evans Tokushima fatty (OLETE; body weight 5--$\pm$30g) male rats, as a model of type 2 diabetes mellitus. Type I diabetes was induced in SD rats by intramuscular injection of alloxan (80 mg/kg BW). Animals were randomly assigned either to continue the ad libitum diet or 40% DR (60% intake of ad libitum diet) groups. The body weight was measured at every 2 weeks to 4 months following DR. The activities of antioxidant enzymes (superoxide dismutase (SOD), catalase, glutathione peroxidase (GSHPx) were measured in liver, lung and erythrocytes and the concentration of TBARS as a marker of reactive oxygen species-induced tissue injry was also measured in rats after 4 months 40% DR. The body weight 4 months after 40% DR of control SD, alloxian-diabetid SD and OLETE rats were 80%, 98% and 75% of each control groups, respectively. The activities of SOD, catalase and GSHPx in lung and erythrocytes of rats were not change by 40% DR but in 4 month 40% DR rat liver, the activities of SOD and catalase were increased in control SD, alloxan-diabetic SD, and OLETF groups. The concentration of TBARS in lung and erythrocytes was also not changed by 40% DR, while liver TBARS concentration was decreased in OLETF and control SD rats compared to each non-DR control rats. These results suggested that the body weight changes in diabetic rats by DR was more prominent in type 2 diabetes and changes of antioxidant enzymes is most prominent in liver by DR either type 1 and 2 diabetic rats.

• Journal of Ginseng Research
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• v.44 no.2
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• pp.267-273
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• 2020

Background: Continuous exposure to high temperatures can lead to heat stress. This stress response alters the expression of multiple genes and can contribute to the onset of various diseases. In particular, heat stress induces oxidative stress by increasing the production of reactive oxygen species. The liver is an essential organ that plays a variety of roles, such as detoxification and protein synthesis. Therefore, it is important to protect the liver from oxidative stress caused by heat stress. Korean ginseng has a variety of beneficial biological properties, and our previous studies showed that it provides an effective defense against heat stress. Methods: We investigated the ability of Korean Red Ginseng and Korean black ginseng extracts (JP5 and BG1) to protect against heat stress using a rat model. We then confirmed the active ingredients and mechanism of action using a cell-based model. Results: Heat stress significantly increased gene and protein expression of oxidative stress-related factors such as catalase and SOD2, but treatment with JP5 (Korean Red Ginseng extract) and BG1 (Korean black ginseng extract) abolished this response in both liver tissue and HepG2 cells. In addition, JP5 and BG1 inhibited the expression of inflammatory proteins such as p-NF-κB and tumor necrosis factor alpha-α. In particular, JP5 and BG1 decreased the expression of components of the NLRP3 inflammasome, a key inflammatory signaling factor. Thus, JP5 and BG1 inhibited both oxidative stress and inflammation. Conclusions: JP5 and BG1 protect against oxidative stress and inflammation induced by heat stress and help maintain liver function by preventing liver damage.

• Journal of Pharmaceutical Investigation
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• v.27 no.3
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• pp.173-179
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• 1997

A water-soluble DDB derivative (Bis{2-(methylamino)ethyl}-4,4-dimethoxy-5,5',6,6'-dimethylenedioxy-biphenyl-2,2'-dicarboxylate, DDB-S) was synthesized and its therapeutic effects on the liver damage induced by carbon tetrachloride in rats were evaluated. Oral administration of DDB-S reduced the aspartate aminotransferase(AST) and alanine aminotransferase(ALT) activities and increased total protein and albumin contents in the serum of the carbon tetrachloride intoxicated rat. Therapeutic effects of DDB-S by intravenous injection was also investigated using carbon tetrachloride intoxicated rats. Histological studies showed that IV injection of DDB-S had improved the typical necrosis around centrilobular area in liver tissue due to the carbon tetrachloride intoxication and also prevented the elevation of liver weigh/body weight ratio. IV administration of DDB-S to $CCl_4-treated$ rats significantly decreased AST & ALT activities and also prevented the decrease of aniline hydroxylation activity of the liver. These results indicate that i.v. administration of DDB-S is very effective in recovering the liver function in $CCl_4-treated$ rats.