• Natural Product Sciences
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• v.12 no.2
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• pp.94-100
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• 2006

The essential oil (EC-oil) obtained from the buds of Eugenia caryophyllata (Myrtaceae) was examined for its free radical-scavenging activity, cytotoxicity, and in vivo toxicity. To find the xenobiotic properties of EC-oil, serum thiobarbituric acid reactive substances (TBARS) level and hepatic drug-metabolizing enzyme activities were measured. It was found that EC-oil displayed xenobiotic properties like bromobenzene. The cytotoxicities of eugenol and of the EC-oil were greatly attenuated by the sulfhydryl-containing N-acetyl-L-cysteine (NAC), suggesting that eugenol was susceptible to nucleophilic sulfhydryl. In addition, eugenol also showed potent free radical-scavenging activity in the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. Moreover, methyleugenol considerably exhibited less cytotoxicity and less potent free radical-scavenging activity than eugenol, and the cell viability of the methyleugenol was more increased with NAC treatment than the eugenol. These results indicate that the phenolic OH in eugenol may play a crucial role in both cytotoxicity and free radical-scavenging activity. The fashion on oxidative stress and hepatic drug-metabolizing enzyme activities of eugenol resembled those of bromobenznene.

• Korean Journal of Pharmacognosy
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• v.17 no.3
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• pp.189-194
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• 1986

The single acute treatment of mice with the steam distillate, non-volatile ether extract and methanol extract from mace, arils of Myristica fragrans(Myristicaceae) caused a significant prolongation of hexobarbital-induced narcosis, an increase in strychnine toxicity as well as a significant decrease in hepatic microsomal drug metabolizing enzyme activities. On seven daily consecutive administrations, however, the duration of narcosis was markedly shortened and significant increases in the hepatic enzyme activities were shown. From the non-volatile ether fraction, macelignan, a new lignan, mp $70{\sim}72^{\circ}$ was isolated as an active principle.

• The Journal of Korean Medicine
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• v.31 no.3
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• pp.128-132
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• 2010

Objectives: This study aimed to review the general features of drug induced liver injury (DILI) and the important factors in consideration of herbal drugs and DILI. Methods: We reviewed general aspects of DILI such as classification, inducible factors, diagnosis methods, prevention, and the status of herbal drug-associated DILI via literature. Results: Besides the drug itself, genetic and environmental factors affect hepatic toxicity. There is a lack of definitive diagnoses of DILI by drugs, including herbal remedies. The possibility of herbal drug-associated DILI is exaggerated, and majority of herbal drug-derived hepatic injury could be easily prevented if Oriental doctors pay attention to this issue. Conclusion: This study can provide Oriental doctors an overview and be helpful in minimizing the episodes of hepatotoxicity in use of herbal drugs.

• Applied Microscopy
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• v.26 no.1
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• pp.1-9
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• 1996

This paper aims to probe the effect of SQ in the rat liver which pretreated with CP was examined by transmission electron microscope. In the A group, the difference between the normal and the treated groups were not detected at 24 hours, but the few mitochondria were expanded at the 72 hours. In the B group, the cisternae of rough-surfaced endoplasmic reticulum were partially destructed and attached ribosomes were remarkably decreased at 24 hours. A number of the mitochondria were dilated and increased in number, the filamentous materials also detected at 72 hours. These results suggest that SQ is not only concerned with construction of the membrane of the cell organelles but also decreased the cellular toxicity in the hepatic cells.

• Korean Journal of Pharmacognosy
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• v.23 no.2
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• pp.81-88
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• 1992

The effects of scoparone, one of coumarin derivative on the hepatic bromobenzene metabolizing enzyme system was estimated in rats. Scoparone pretreatment revealed dose-dependently the recovery of decrease in epoxide hydrolase activity due to the bromobenzene(310 mg/kg, i.p.) treatment. And also scoparone and scopoletin (each 5mg/kg, p.o.) pretreatments showed two times increase in the $V_{max}$ values compared to those of bromobenzene-treated group which were calculated from tripartite reciprocal plots. The mode of protective effect of scoparone against bromobenzene induced toxicity is considered to be due to the induction of microsomal enzyme activity by scopoletin, the intermediate metabolite of scoparone. The changes in cytochrome P-450 activity, aminopyrine N-demethylation, aniline hydroxylation and glutathione S-transferation in scoparone-treated group were not significantly different from those of the control group.

• Radiation Oncology Journal
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• v.33 no.4
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• pp.276-283
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• 2015

Purpose: We evaluated the efficacy and toxicity of repeated high dose 3-dimensional conformal radiation therapy (3D-CRT) for patients with unresectable hepatocellular carcinoma. Materials and Methods: Between 1998 and 2011, 45 patients received hepatic re-irradiation with high dose 3D-CRT in Samsung Medical Center. After excluding two ineligible patients, 43 patients were retrospectively reviewed. RT was delivered with palliative or salvage intent, and equivalent dose of 2 Gy fractions for ${\alpha}/{\beta}=10Gy$ ranged from $31.25Gy_{10}$ to $93.75Gy_{10}$ (median, $44Gy_{10}$). Tumor response and toxicity were evaluated based on the modified Response Evaluation Criteria in Solid Tumors criteria and the Common Terminology Criteria for Adverse Events (CTCAE) ver. 4.0. Results: The median follow-up duration was 11.2 months (range, 4.1 to 58.3 months). An objective tumor response rate was 62.8%. The tumor response rates were 81.0% and 45.5% in patients receiving ${\geq}45Gy_{10}$ and $<45Gy_{10}$, respectively (p = 0.016). The median overall survival (OS) of all patients was 11.2 months. The OS was significantly affected by the Child-Pugh class as 14.2 months vs. 6.1 months (Child-Pugh A vs. B, p < 0.001), and modified Union for International Cancer Control (UICC) T stage as 15.6 months vs. 8.3 months (T1-3 vs. T4, p = 0.004), respectively. Grade III toxicities were developed in two patients, both of whom received ${\geq}50Gy_{10}$. Conclusion: Hepatic re-irradiation may be an effective and tolerable treatment for patients who are not eligible for further local treatment modalities, especially in patients with Child-Pugh A and T1-3.

• Journal of the Korean Society of Food Science and Nutrition
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• v.21 no.3
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• pp.231-240
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• 1992

Effects of dietary protein levels on the manifestations of the toxicity of gramoxone, a bipyridine herbicide, in the liver of rats were investigated. The addition of gramoxone, with regard to the body weight and feed efficiency ratio of rats, had a move dramatic effect on animals fed a low or intermediate protein diet than for those similarly treated among rats fed a relatively high protein diet. Lipid content in the rat liver tended to increase with the addition of gramoxone into each protein diet, with the exception of the high protein-gramoxone diet. The addition of gramoxone tended to increase hepatic TBA value significantly in rats, especially among those fed the low protein-gramoxone diet or the control-gramoxone diet. Significant morphological changes, including fat changes of hepatic cells and increases in the number of Kupffer cells, were found both in rats fed the low protein diet and those fed any of the gramoxone-treated diets. fat changes within hepatic cells were found to be especially severe in rats fed the low protein-gramoxone diet. Distributions of glycogen in rat liver appeared to increase in rats fed any of the diets to which gramoxone had been added.

• Molecular & Cellular Toxicology
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• v.3 no.3
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• pp.177-184
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• 2007

As a possible feasibility of the extrapolation between in vivo and in vitro systems, we investigated the global gene expression from both mouse liver and mouse hepatic cell line treated with hepatotoxic chemical, acetaminophen (APAP), and compared between in vivo and in vitro genomic profiles. For in vivo study, mice were orally treated with APAP and sacrificed at 6 and 24 h. For in vitro study, APAP were administered to a mouse hepatic cell line, BNL CL.2 and sampling was carried out at 6 and 24 h. Hepatotoxicity was assessed by analyzing hepatic enzymes and histopathological examination (in vivo) or lactate dehydrogenase (LDH) assay and morphological examination (in vitro). Global gene expression was assessed using microarray. In high dose APAPtreated group, there was centrilobular necrosis (in vivo) and cellular toxicity with the elevation of LDH (in vitro) at 24 h. Statistical analysis of global gene expression identified that there were similar numbers of altered genes found between in vivo and in vitro at each time points. Pathway analysis identified glutathione metabolism pathway as common pathways for hepatotoxicty caused by APAP. Our results suggest it may be feasible to develop toxicogenomics biomarkers or profiles by comparing in vivo and in vitro genomic profiles specific to this hepatotoxic chemical for application to prediction of liver toxicity.

• Journal of Haehwa Medicine
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• v.22 no.1
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• pp.171-184
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• 2013

Single-and repeated-dose toxicities of Compound K (CK) were evaluated according to Toxicity Test Guidelines of Korea Food and Drug Administration using Sprague-Dawley rats. For single-dose toxicity study, CK was dissolved in drinking water, orally administered and examined for 14 days. As results, CK up to a dose of 5,000 mg/kg, the limited dose, neither induced death, clinical signs and necropsy findings, nor affected body weight gain and organ weights, in which 10% lethal dose could not be estimated. Based on the results of single-dose toxicity test, CK was administered at doses of 500, 1,000 or 2,000 mg/kg for 28 days for the evaluation of repeated-dose toxicity. All doses including the limited dose (2,000 mg/kg) of CK did not cause any abnormalities of rats, including mortality, clinical signs, body weight gain, feed/water consumption, necropsy findings, organ weights, hematology, blood biochemistry. Rather, high doses (1,000 - 2,000 mg/kg) of CK reduced the serum levels of alanine transaminase (ALT), aspartate transaminase (AST), creatinine phosphokinase (CPK), lactate dehydrogenase (LDH) and triglycerides, in addition to an increase in glucose, indicative of protective effects on hepatic and muscular injuries. Thus, both maximum tolerable dose (MTD) and no observed adverse effect level (NOAEL) were not determined. The results indicate that long-term intake of high-dose CK might not induce general adverse effects.

• Proceedings of the Ginseng society Conference
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• 1990.06a
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• pp.132-136
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• 1990

The metabolic disturbance and nephrotoxicity induced by sodium dichromate (20 mg/kg, SC) have been diminished by the administration of Korean red ginseng extract (100 mg/kg, PO). Red ginseng has a powerful potency on the blood urea nitrogen (BUN) increment shown in the early 2h after dichromate intoxication. It normalized the dichromate induced hepatic glycogenolysis. The effect of red ginseng on dichromate induced nephrotoxicity was investigated by hematological analysis, and urinalysis. Ginseng treatment significantly reduced the increases in the urinary excretion of protein and glucose. These effects were dose dependent. Ginseng protected the accumulation of BUN and cretonne in the blood, caused by dichromate intoxication. Unlike CaEDTA, ginseng did not change the urinary excretion chromium. And it could not convert htxavalent chromium to trivalent chromium. These results suggest that ginseng treatment is effective in decreasing the metabolic disturbance, one of the earliest signs of dichromate toxicity, resulting in the protective effect of dichromate induced renal damage.