• 한국식품영양과학회지
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• 제20권2호
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• pp.121-125
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• 1991

This study designs to investigate effects of onion diet on carbon tetrachloride toxicity of rats. Experiments were performed with week's feeding, body weight, food intake, ratio of orgen weight/dody weight, serum lipid levels, superoxide dismutase and catalase activity and malondialdehyde(MDA) content in liver and kidney were determined. The content of serum total cholesterol in each group were lower than those of control group(p<0.05), especially at onion juice treated group. Serum HDL-cholesterol level of CBB and CBJ groups was significantly lower than that of control group (p<0.05). Superoxide dismutase activities of liver and kidney were significantly increased by carbon tetrachloride treatment and decreased by onion feeding. MDA contents in liver and kidney of CCl4 treated rats were significantly decreased by boiled and fresh onion fed group, compared with CCl4 treated control group. This result suggested that onion diet has a protective effect of CCl4 induced hepatotoxicity and nephrotoxicity of rat.

• Molecular & Cellular Toxicology
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• 제1권3호
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• pp.203-208
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• 2005

Thioacetamide (TA) is potent haptotoxincant that requires metabolic activation by mixed-function oxidases. Micrcarray technology, which is massive parallel gene expression profiling in a single hybridization experiment, has provided as a powerful molecular genetic tool for biological system related toxicant. In this study we focus on the use of toxicogenomics for the determination of gene expression analysis associated with hepatotoxicity in rat liver epithelial cell line WB-F344 (WB). The WB cells was used to assess the toxic effects of TA. WB cells were exposed to two concentrations of TA-doses which caused 20% and 50% cell death were chosen and the cells exposed for periods of 2 and 24 h. Our data revealed that following the 2-h exposure at the both of doses and 24-h exposure at the low doses, few changes in gene expression were detected. However, after 24-h exposure of the cells to the high concentration, multiple changes in gene expression were observed. TA treatment gave rise predominantly to up-regulation of genes involved in cell cycle and cell death, but down-regulation of genes involves in cell adhesion and calcium ion binding. Exposure of WB cells to higher doses of the TA gave rise to more changes in gene expression at lower exposure times. These results show that TA regulates expression of numerous genes via direct molecular signaling mechanisms in liver cells.

• Genomics & Informatics
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• 제8권1호
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• pp.41-49
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• 2010

Statins are competitive inhibitors of hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase and used most frequently to reduce plasma cholesterol levels and to decrease cardiovascular events. However, statins also have been reported to have undesirable side effects such as myotoxicity and hepatotoxicity associated with their intrinsic efficacy mechanisms. Clinical studies recurrently reported that statin therapy elevated the level of liver enzymes such as ALT and AST in patients suggesting possible liver toxicity due to statins. This observation has been drawn great attention since statins are the most prescribed drugs and statin-therapy was extended to a larger number of high-risk patients. Here we employed rat primary hepatocytes and microarray technique to understand underlying mechanism responsible for statin-induced liver toxicity on cell level. We isolated genes whose expressions were commonly modulated by statin treatments and examined their biological functions. It is of interest that those genes have function related to response to stress in particular immunity and defense in cells. Our study provided the basic information on cellular mechanism of statin-induced cytotoxicity and may serve for finding indicator genes of statin -induced toxicity in rat primary hepatocytes.

• 한국식품위생안전성학회지
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• 제18권3호
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• pp.166-170
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• 2003

삼백초가 TCDD 투여로 유발된 rat의 지질대사에 미치는 효과를 알아보기 위해 NTT, TTA, STT군으로 각각 10마리씩 나누어 TCDD를 투여하고 4주 동안 물질을 투여하였다. 4주 후 희생시켜서 혈청과 간의 지질대사를 관찰한 결과는 다음과 같다. 1. Total Cholesterol에서 삼백초를 투여한 STT군은 NTT군 비교해서 14.46% 증가하였으며, 혈청 중의 HDL-Cholesterol은 SST군이 TTA군과 비교하여 21.29% 증가하였고 94.98%로 엑제되었다. LDL-Cholesterol에서는 STT군이 TTA군 보다 12.86% 감소하였으며, 48.34%로 억제되었다. 2. 혈청중의 TG의 함량은 TTA군이 NTT군에 비해 34.84% 증가하였다. TTA 군에 비해 STT군은 7.06% 감소하였으며, 18.9% 억제시킨다 3. 간조직 중의 MDA량은 STT군이 TTA군에 비해 17.14% 감소하였고, 32.72%의 억제율을 보였다.

• Biomolecules & Therapeutics
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• 제4권3호
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• pp.244-250
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• 1996

In this study, the anti-lipidperoxidative effects of G009, a polysaccharide extracted from Ganoderma lucidum IY009, was determined in ascorbic acid-$Fe^{2+}$-adenosine 5-diphosphate-intoxicated rat. In a model of ascorbic acid-Fe$^{2+}$-adenosine 5-diphosphate-induced hepatotoxicity in rat, G009 exhibited anti-lipidperoxidative effect in rat liver homogenate, and that malondialdehyde values of the liver homogenate inhibited from 48.1% to 74.8% in comparison to controls (p<0.05). The malondialdehyde formation in serum inhibited 66.5% at 100 mg/kg of G009. Also, serum levels of glutamic oxaloacetic transaminase and glutamic pyruvic transaminase in peroxidizer-induced rats treated with G009 was decreased compared with control. Especially, the formation of lipid peroxides in serum was related to glutamic pyruvic transaminase levels. These results suggest that G009 has a protective effect on ascorbic acid-$Fe^{2+}$-adenosine 5-diphosphate-induced hepatic injury through an inhibition of lipid peroxidation in liver.r.

• 한국자원식물학회지
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• 제19권6호
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• pp.649-654
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• 2006

The objective of present study was to investigate the anti oxidative and hepatoprotective effects of tomato extracts. Total antioxidant capacity and total antioxidant response were 5.5 and $19.8{\mu}g$ Trolox equivalent per mg of tomato extract, respectively. DPPH radical scavenging activity of tomato extracts ($10mg\;ml^{-1}$) was 70% as compared to 100% by pyrogallol solution as a reference. The effect of the tomato extracts on lipid peroxidation was examined using rat liver mitochondria induced by iron/ascorbate. Tomato extracts at the concentration of $0.5mg\;ml^{-1}$ significantly decreased TBARS concentration. Tomato extracts prevented lipid peroxidation in a dose-dependent manner. The effect of the tomato extracts on reactive oxygen species (ROS) generation was examined using cell-free system induced by $H_2O_2/FeSO_4$. Addition of $1mg\;ml^{-1}$ of tomato extracts significantly reduced dichlorofluorescein (DCF) fluorescence. Tomato extracts caused concentration-dependent attenuation of the increase in DCF fluorescence, indicating that tomato extracts significantly prevented ROS generation in vitro. The effect of tomato extracts on cell viability and proliferation was examined using hepatocyte culture. Primary cultures of rat hepatocytes were incubated with 1mM tert-butyl hydroperoxide (t-BHP) for 90 min in the presence or absence of tomato extracts. MTT values by addition of tomato extracts at the concentration of 2, 10, and $20mg\;ml^{-1}$ in the presence of t-BHP were 13, 33 and 48%, respectively, compared to 100% as control. Tomato extracts increased cell viability in a dose-dependent manner. These results demonstrate that tomato extracts suppressed lipid peroxidation and t-BHP-induced hepatotoxicity and scavenged ROS generation. Thus antioxidant and hepatoprotective effects of tomato extracts seem to be due to, at least in part, the prevention from free radicals-induced oxidation, followed by inhibition of lipid peroxidation.

• Archives of Pharmacal Research
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• 제22권5호
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• pp.474-478
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• 1999

Modulation of unscheduled DNA synthesis by dehydroepiandrosterone (DHEA) after exposure to various chemical carcinogens was investigated in the primary rat hepatocytes. Unscheduled DNA synthesis was induced by treatment of such direct acting carcinogens as methly methanesulfonate (MMS) and ethyl methanesulfonate (EMS) or procarcinogens including benzo(a)pyrene (BaP) and 7, 12-dimethylbenz(a)anthracene (DMBA). Unscheduled DNA synthesis was determined by measuring [methyl-3H]thymidine radioactivity incorporated into nuclear DNA of hepatocytes treated with carcinogens in the presence or absence of DHEA. Hydroxyurea $(5{\times}10^{-3} M)$was added to growth medium to selectively suppress normal replication. DHEA at concentrations ranging from $(1{\times}10^{-6} M)$ to$(5{\times}10^{-4} M)$ did not significantly inhibit unscheduled DNA synthesis induced by either MMS $(1{\times}10^{-4} M)$ or EMS $(1{\times}10^{-2} M)$. In contrast, DHEA-significantly inhibited unscheduled DNA synthesis induced by BaP $(6.5{\times}10^{-5} M)$ and DMBA.$(2{\times}10^{-5} M)$. DHEA-induced hepatotoxicity in rats was examined using lactate dehydrogenase (LDH) release as an indicator of cytotoxicity. DHEA exhibit no significant increase in LDH release compared with the control at 18 h. These data suggest that nontoxic concentration of DHEA does not affect the DNA excision repair process, but it probably influence the enzymatic system responsible for the metabolic activation of procarcinogens and thereby decreases the amount of the effective DNA adducts formed by the ultimate reactive carcinogenic species.

• Bulletin of the Korean Chemical Society
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• 제27권9호
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• pp.1386-1392
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• 2006

Kahweol and cafestol significantly reduced t-BHP-induced oxidative injuries in cultured rat hepatocytes, as determined by cell cytotoxicity, intracellular glutathione (GSH) content and lipid peroxidation in a dose-dependent manner. In addition, kahweol and cafestol provided good protection from the t-BHPinduced production of intracellular reactive oxygen species and DNA damage. The in vivo study showed that pretreatment with kahweol and cafestol prior to the administration of t-BHP significantly prevented the increase in serum levels of hepatic enzyme markers (alanine aminotransferase and aspartate aminotransferase) and reduced oxidative stress, such as GSH content and lipid peroxidation, in the liver in a dose-dependent manner. The histopathological evaluation of the livers also revealed that kahweol and cafestol reduced the incidence of liver lesions induced by t-BHP. Taken together, these results support the anti-oxidative role of kahweol and cafestol and demonstrate that kahweol and cafestol can protect hepatocytes from oxidative stress.

• Biomolecules & Therapeutics
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• 제17권4호
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• pp.455-460
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• 2009

Foods of plant origin, especially fruits and vegetables, have attracted attention because of their potential benefits to human health. In this report, Rubi Fructus (RF), the dried unripe fruit of Rubus coreanus Miq (Rosaceae) and ellagic acid (EA) purified from RF were used to test their potential hepatoprotective effect against acetaminophen (AAP)-induced hepatotoxicity in rats. RF extract (RFext) and EA reduced the elevated levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) in serum and the content of lipid peroxide in liver by AAP administration, while the increment of the cellular glutathione (GSH) content and the induction of glutathione S-transferase (GST) and glutathione peroxidase (GSH-PX) which were decreased by AAP administration. RFext and EA from RFext did not affect the two major form of cytochrome P450s, cytochrome P450 2E1 (CYP2E1) and cytochrome P450 1A2 (CYP1A2), but downregulated the cytochrome P450 3A4 (CYP3A4) related to the conversion of AAP to N-acetyl-P-benzoquinone imine (NAPQI). These results suggest that RFext and EA from RF exhibit a hepatoprotective effect not only by increasing antioxidant activities but also by down-regulating CYP3A4 in the AAP-intoxicated rat.

• Korean Journal of Acupuncture
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• 제25권2호
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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.