• Biomolecules & Therapeutics
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• v.16 no.3
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• pp.197-202
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• 2008

In our previous publication we compared the gene expression profiles on hepatotoxicants exposure to assess the comparability between in vivo and in vitro test systems. We investigated global gene expression from both mouse liver and mouse hepatic cell line treated with thioacetamide (TAA) and identified several common genes. In this study, we selected genes to validate them as potential biomarkers for hepatotoxicity on the relevance of in vitro and in vivo system. Three up-regulated, aquaporin 8 (Aqp8), glutathione peroxidase 1 (Gpx1), succinate-CoA ligase, GDP-forming, alpha subunit (Suclg1) and two down-regulated, DnaJ (Hsp40) homolog subfamily C member 5 (Dnajc5) and tumor protein D52 (Tpd52) genes were tested for their effects in vitro. For characterization of gene function, short interfering RNA (siRNA) for each gene was synthesized and transfected in mouse hepatic cell line, BNL CL.2. Cell viability, mRNA expression level and morphological alterations were investigated. We confirmed siRNA transfection against selected five genes induced down-regulation of respective mRNA expression. siRNA transfection in general decreased cell viability in different degrees and induced morphological changes such as membrane thickening and alterations of intracellular structures. This suggests that these genes could be associated with TAA-induced toxicity. Furthermore, these genes may be used in the investigation of hepatotoxicity for better understanding of its mechanism.

• Journal of the Korean Society of Food Science and Nutrition
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• v.37 no.5
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• pp.548-554
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• 2008

The aim of this study was to identify the inhibitory effect of hepatic toxicity and liver lipid metabolism after the administration of Artemisia capillaris and Paecilomyces japonica. SD rats were divided into $CCI_4$ treated group with subgroups of 6% Artemisia capillaries (6A), 4% Artemisia capillaris＋2% Paecilomyces japonica (4A2P), 3% Artemisia capillaris＋3% Paecilomyces japonica (3A3P), 2% Artemisia capillaris＋4% Paecilomyces japonica (2A4P) and 6% Paecilomyces japonica (6P). In this study we also intended to verify the optimum ratio of Artemisia capillaris and Paecilomyces japonica which can reduce hepatotoxicity. Artemisia capillaris and Paecilomyces japonica reduced cholesterol and triglyceride levels which were increased by the treatment of $CCI_4$. HDL-cholesterol level was the most enhanced in the group of 4A2P. On the other hand, athrogenic index (AI) was reduced statistically (p<0.05). When the ratio of Artemisia capillaris and Paecilomyces japonica was 2:1, the improvement of rat serum and liver lipid metabolism and the alleviation of hepatic damage induced by $CCI_4$ were shown to be the most effective in this study. It is considered that the symptoms of severe chemically induced hepatotoxicity could be lessened by Artemisia capillaris and Paecilomyces japonica administration.

• Applied Microscopy
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• v.38 no.1
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• pp.1-10
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• 2008

Dandelion has been frequently used as a remedy for women's disease, inflammatory diseases and disorders of the liver and gallbladder. Dandelion extracts water extract, an herbal medication, may have an effect on the activity of hepatic antioxidant enzymes in diabetic rat. This study aims demonstrate the effect of dandelion extracts, one of the natural chelator, on the biochemical and enzyme activity changes in the mouse liver caused by $HgCl_2$. Mice approximately 30 gm in weight were grouped into the control, mercury chloride-treated, and the dandelion extracts-treated after mercury chloride groups. $HgCl_2$ (5 mg/kg) and dandelion extracts (3 g/kg) were delivered orally. Serum AST and ALT were measured, enzyme activity of liver were examined by spectrophotometer and ultrastructural alteration of liver were examined by light and electron microscopy. Dandelion extracts were decreased the increase of serum AST and ALT level induced by mercury. The catalase activity was decreased in the dandelion extracts group. The activity of SOD was dereased, but did not show significant differences. Mercury chloride-treated hepatic cell were irregular nucleus, enlarged and reduced number of mitochodria, enlarged rough endoplasmic reticulum, loss of ribosomes. Cells treated with dandelion extracts were similar to those of the control group. In conclusion, dandelion extracts may protect the mercury-induced toxicity on Liver.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.6
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• pp.805-811
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• 2016

This study was conducted to investigate the protective effects of water extract from Crassostrea gigas (CGW) against ethanol-induced hepatic toxicity in rats. Seventy-two male Wistar rats (6-week-old) were divided into six groups of 12 animals each: control group (1 mL saline/d), ethanol-treated group, positive control group (ethanol+Hovenia dulcis Thunb extract), CGWL group (ethanol+low dosage of CGW), CGWM group (ethanol+medium dosage of CGW), and CGWH group (ethanol+high dosage of CGW). All groups except the control group received ethanol (40% ethanol 5 g/kg) orally. CGW administration with ethanol resulted in prevention of ethanol-induced hepatotoxicity by increasing levels of serum alanine aminotransferase and ${\gamma}-glutamyltransferase$. CGW supplementation significantly reduced formation of malonaldehyde and inhibited reduction of hepatic glutathione and peroxidase levels, as compared with the ethanol-administration group. Further, CGW suppressed expression of CYP2E1, which was elevated by ethanol administration. Consequently, our results indicate that Crassostrea gigas may exert hepatoprotective effects against alcohol-induced hepatocyte injury by intensifying the anti-oxidative defense system.

• Korean Journal of Food Science and Technology
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• v.31 no.3
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• pp.831-837
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• 1999

Ochratoxin A (OA), a naturally occurring mycotoxin, has been known to cause renal and hepatic lesion in human and animals. This study was carried out to investigate the modulation effects of antioxidant vitamins on OA-induced lipid peroxidation associated with oxidative damage. Vitamin C (10 mg/kg/day) and vitamin E (63.8 mg/kg/day) were administered by intraperitoneal (i.p.) injection to male ICR mice, and 1 hr later, OA which was dissolved in 0.1 M $NaHCO_3$, treated 4 mg/kg/day by i.p. injection. During 4 days repeated, and then measured superoxide dismutase (SOD) activity, catalase activity and malondialdehyde (MDA) formation in microsomes of liver and kidney. Additionally, the relationship between cell damage and modulation effects of antioxidant vitamins was evaluated by comet assay. Results were as followed; i) SOD, catalase activity and MDA level were significantly increased by OA treated, ii) SOD, catalase activity and MDA formation were significantly decreased by antioxidant vitamins combine treated, iii) blood cell damage associated with lipid peroxidation, induced by OA, also modulated by antioxidant vitamins. These results indicated that antioxidant vitamins might be used for prevention of renal and hepatic damage due to ochratoxicosis.

• The Korean Journal of Pharmacology
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• v.11 no.1 s.17
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• pp.47-53
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• 1975

The metabolism of many drugs and also of steroid hormones is mediated by enzymes located in the microsomal fraction in smooth surfaced endoplasmic reticulum of mammalian liver. The duration and intensity of action of many drugs are largely determined by the speed at which they are metabolized in the body. Repeated administration of phenobarbital results in the induction of enzymes that metabolize a number of drugs. Lee et al. reported that daily administration of phenobarbital in rats significantly increased the activities of amylase in the pancreatobiliary juice, but the concentration of cholate in the bile was significantly lower in the treated group than that in the control group. After animals were treated with $CCl_4$, histological changes were shown in the endoplasmic reticulum, decreased microsomal enzyme activity and decreased hepatic protein synthesis were apparent. The purpose of the present report was to study the interaction between a 'microsomal-stimulating' agent such as phenobarbital and a 'microsomal- depressing' agent such as $CCl_4$ on hepatic and pancreatic functions in rats. The results obtained are summarized as follows: 1. The mortality rate of $CCl_4$ treated group was 34% and was decreased this figure to 15% with phenobarbital pretreatment. 2. In animals treated with phenobarbital the volume of biliary-pancreatic secretion was markedly elevated but the volume was decreased significantly in animals treated with $CCl_4$. 3. Total bilirubin output was elevated markedly in the $CCl_4$ treated group of rats pretreated with phenobarbital. The bilirubin concentration was increased in $CCl_4$ treated group and decreased in the group treated phenobarbital alone. 4. The concentration and total output of cholate in the bile were significantly lower in the all experimental group than control group. 5. In the animals treated with phenobarbital alone and phenobarbital plus $CCl_4$, the activity of lipase in pancreatobiliary juice was elevated, while in the animals treated with $CCl_4$ alone no change was observed. 6. The activity of amylase in the pancreatobiliary juice was decreased in the $CCl_4$ treated group, but elevated markedly in phenobarbital group and also elevated in phenobarbital-$CCl_4$ group. By the above results, it is concluded, when the liver was damaged by $CCl_4$, the exocrine function of pancreas and liver was decreased simultaneously. However, in the animals pretreated with phenobarbital, the toxicity of $CCl_4$ on the liver and pancreas was reduced.

• Journal of Ginseng Research
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• v.23 no.3 s.55
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• pp.182-189
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• 1999

For the determination of anti oxidative effects of Korean red ginseng extracts, 100 mg/kg body weight of paraquat(1,1-dimethyl-4,4-bipyrimidinium dichloride) was injected to peritoneal cavity of 6 weeks 23-27 g of ICR mail mice which were pretreated with 200 mg/kg body weight of korean red ginseng extracts(total saponin, water extracts, alcohol extracts, lipophilic extracts) and ascorbic acid for 5 days. Most of mice died of paraquat toxicity within 4 days except only $30\%$ of ascorbic acid group. The hepatic total-SOD activity in liver was highest in ascorbic acid group and lipophilic ginseng extracts group next (p<0.0l). The level of hepatic hydroperoxide was lowest in the order of in alcohol extracts group, lipophilic extracts group and ascorbic acid group (p<0.0l). The highest catalase activity was induced by ascorbic acid followed by water extracts and lipophillic extracts (p<0.01). Finally, the lipid peroxidation level (malondialdehyde:MDA) was the lowest in water extracts group and ascorbic acid next (p<0.01). The highest MDA level was appeared in praquat group and next total saponin group next. In conclusion, the order of effectiveness of antioxidants was found to be ginseng water extracts> ascorbic acid> lipophillic extracts> other ginseng extracts. It was also found that any predominant antioxidant was not effective evenly to all of antioxidant test.

• Journal of Ginseng Research
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• v.26 no.3
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• pp.139-144
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• 2002

Pregnancy is a physiological state accompained by a high energy demand of many bodily functions and an increased oxygen requirement. Because of the increased intake and utilization of oxygen, increased levels of oxidative stress would be expected. So we observed the activities of the hepatic antioxidant enzymes from rat treated with total saponin from the red ginseng against free raicals produced in pregnant rats. The activity of superoxide dismutase (SOD) in the control group was slightly decreased during pregnancy, and SOD activity in total saponin treated group was not observed any siginificant change compared with the control group. The activities of glutathione peroxidase (GPX), glutathione reductase (GRD) and catalase in the control group have shown the decreasing tendency during pregnancy, whereas the activities of GRD and catalase in total saponin treated group showed significant increased tendency compared with the control group. GPX activity in total saponin treated group was slightly decreased tendnency compared with the control group. The activity of glutathione-S-transferase (GST) in the control group was increased to keep the state of homaeostasis tendency in pregnant rats. On the other hand, the activity of GST after total saponin treatment was increased than control group. Activity of all enzymes in the control group and total saponin treated group recovered the normal level after delivery of rats. In spite of the physiological changes in vivo, the inflaunce of total saponin on activaties of hepatic antioxidant enzyme in pregnant rats seems to be regulated the biological homeostatic adaptation mechanism which protects the maternal liver aganist oxygen induced toxicity

• Journal of The Korean Society of Clinical Toxicology
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• v.17 no.2
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• pp.58-65
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• 2019

Purpose: Alpha-amanitin induces potent oxidative stress and apoptosis, and may play a significant role in the pathogenesis of hepatotoxicity. This study examined the mechanisms of α-amanitin-induced apoptosis in vitro, and whether green tea extract (GTE) offers protection against hepatic damage caused by α-amanitin (AMA) induced apoptosis in vivo. Methods: The effects of GTE and SIL on the cell viability of cultured murine hepatocytes induced by AMA were evaluated using an MTT assay. Apoptosis was assessed by an analysis of DNA fragmentation and caspase-3. In the in vivo protocol, mice were divided into the following four groups: control group (0.9% saline injection), AMA group (α-amanitin 0.6 mg/kg), AMA+SIL group (α-amanitin and silibinin 50 mg/kg), and AMA+GTE group (α-amanitin and green tea extract 25 mg/kg). After 48 hours of treatment, the hepatic aminotransferase and the extent of hepatonecrosis of each subject was evaluated. Results: In the hepatocytes exposed to AMA and the tested antidotes, the cell viability was significantly lower than the AMA only group. An analysis of DNA fragmentation showed distinctive cleavage of hepatocyte nuclear DNA in the cells exposed to AMA. In addition, the AMA and GTE or SIL groups showed more relief of the cleavage of the nuclear DNA ladder. Similarly, values of caspase-3 in the AMA+GTE and AMA+SIL groups were significantly lower than in the AMA group. The serum AST and ALT levels were significantly higher in the AMA group than in the control and significantly lower in the AMA+GTE group. In addition, AMA+GTE induced a significant decrease in hepatonecrosis compared to the controls when a histologic grading scale was used. Conclusion: GTE is effective against AMA-induced hepatotoxicity with its apoptosis regulatory properties under in vitro and in vivo conditions.

• The Journal of Internal Korean Medicine
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• v.44 no.3
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• pp.439-454
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• 2023

Objectives: As Korea transitions into an aging society, the incidence of cerebrovascular disease is expected to increase. Herbal medicine is commonly used in Oriental medicine to treat cerebrovascular disease. However, there is insufficient clinical evidence to actively support the safety of herbal medicine in clinical practice. Therefore, the aim of this study was to determine the toxicity and safety of four herbal medicines (Cheongsimyeonja-tang, Dodam-tang, Hyeolbuchukso-tang, and Boshiniknai-tang) in patients with cerebrovascular disease. Methods: This study used electronic medical records to analyze patients admitted to an oriental medicine hospital from April 1, 2017, to December 31, 2020. Liver and renal function values at the time of admission and discharge were compared. Results: A total of 25 patients were included in this study. We found no significant differences in various variables, such as complete blood count, liver-renal function test, and urine, before and after the administration of the four herbal medicines. Additionally, no significant adverse events related to herbal medicine were observed. Conclusions: This study confirmed the safety of the four herbal medicines in patients with cerebrovascular disease who were hospitalized in a single Oriental medicine hospital.