• BMB Reports
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• v.46 no.10
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• pp.513-518
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• 2013

We investigated the protective effects of Gymnaster koraiensis against oxidative stress-induced hepatic cell damage. We used two different cytotoxicity models, i.e., the administration of tert-butyl hydroperoxide (t-BHP) and acetaminophen, in HepG2 cells to evaluate the protective effects of G. koraiensis. The ethyl acetate (EA) fraction of G. koraiensis and its major compound, 3,5-di-O-caffeoylquinic acid (DCQA), exerted protective effects in the t-BHP-induced liver cytotoxicity model. The EA fraction and DCQA ameliorated t-BHP-induced reductions in GSH levels and exhibited free radical scavenging activity. The EA fraction and DCQA also significantly reduced t-BHP-induced DNA damage in HepG2 cells. Furthermore, the hexane fraction of G. koraiensis and its major compound, gymnasterkoreayne B (GKB), exerted strong hepatoprotection in the acetaminophen-induced cytotoxicity model. CYP 3A4 enzyme activity was strongly inhibited by the extract, hexane fraction, and GKB. The hexane fraction and GKB ameliorated acetaminophen-induced reductions in GSH levels and protected against cell death.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.7
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• pp.4441-4446
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• 2013

Cholangiocarcinoma (CCA) is a tumor of biliary ducts, which has a high mortality rate and dismal prognosis. Constitutively activation of the transcription factor nuclear factor kappa-B (NF-${\kappa}B$) has been previously demonstrated in CCA. It is therefore a potential target for CCA treatment. Effects of diethyldithiocarbamate (DDTC) on NF-${\kappa}B$-dependent apoptosis induction in cancer have been reported; however, anti-metastasis has never been addressed. Therefore, here the focus was on DDTC effects on CCA migration and adhesiond. Anti-proliferation, anti-migration and anti-adhesion activities were determined in CCA cell lines, along with p65 protein levels and function. NF-${\kappa}B$ target gene expression was determined by quantitative RT-PCR. DDTC inhibited CCA cell proliferation. Suppression of migration and adhesion were observed prior to anti-CCA proliferation. These effects were related to decreased p65, reduction in NF-${\kappa}B$ DNA binding, and impaired activity. Moreover, suppression of ICAM-1 expression supported NF-${\kappa}B$-dependent anti-metastatic effects of DDTC. Taken together, DDTC suppression of CCA migration and adhesion through inhibition of NF-${\kappa}B$ signaling pathway is suggested from the current study. This might be a promising treatment choice against CCA metastasis.

• Archives of Pharmacal Research
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• v.27 no.3
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• pp.340-345
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• 2004

Our work in this study was made in the microsomal fraction to evaluate the lipid peroxidation by measuring superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and malondialdehyde (MDA) and to elucidate the preventive role of CS in the $CCl_4$-induced oxidative stress. The excessive lipid peroxidation by free radicals derived from $CCl_4$ leads to the condition of oxidative stress which results in the accumulation of MDA. MDA is one of the end-products in the lipid peroxidation process and oxidative stress. MDA, lipid peroxide, produced in this oxidative stress causes various diseases related to aging and hepatotoxicity, etc. Normal cells have a number of enzymatic and nonenzymatic endogenous defense systems to protect themselves from reactive species. The enzymes in the defense systems, for example, are SOD, CAT, and GPx. They quickly eliminate reactive oxygen species (ROS) such as superoxide anion free radicalㆍO$^{[-10]}$ $_2$, hydrogen peroxide $H_2O$$_2$ and hydroxyl free radicalㆍOH. CS inhibited the accumulation of MDA and the deactivation of SOD, CAT and GPx in the dose-dependent and preventive manner. Our study suggests that CS might be a potential scavenger of free radicals in the oxidative stress originated from the lipid peroxidation of the liver cells of $CCl_4$-treated rats.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.13
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• pp.5515-5519
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• 2015

The single nucleotide polymorphism (SNP) ss469415590 in the interferon lambda-4 (IFNL4) gene has recently been reported to have an association with treatment response in chronic hepatitis C. However, any importance of the SNP in association with response to pegylated interferon (PEG-IFN) therapy in patients with chronic hepatitis B (CHB) is unclear. We retrospectively analyzed data for Thai patients with CHB treated with PEG-IFN for 48 weeks. Virological response (VR) for HBeAg-positive CHB was defined as HBeAg seroconversion plus HBV DNA level <2,000 IU/mL at 24 weeks post-treatment. VR for HBeAg-negative CHB was defined as an HBV DNA level <2,000 IU/mL at 48 weeks. The SNP was identified by real time PCR using the TaqMan genotyping assay with MGB probes. A total 254 patients (107 HBeAg-positive and 147 HBeAg-negative) were enrolled in the study. The distribution of TT/TT, ${\Delta}G/TT$ and ${\Delta}G/{\Delta}G$ genotypes was 221 (87.0%), 32 (12.6%) and 1 (0.4%), respectively. Patients with non-TT/TT genotypes had significantly higher baseline HBV DNA levels than patients with the TT/TT genotype. In HBeAg-positive CHB, 41.2% of patients with TT/TT genotype versus 50.0% with non-TT/TT genotype achieved VR (P=0.593). In HBeAg-negative CHB, the corresponding figures were 40.3% and 43.5%, respectively (P=0.777). There was no significant correlation between the SNP genotypes and HBsAg clearance in both groups of patients. In summary, ss469415590 genotypes were not associated with response to PEG-IFN in Thai patients with HBeAg-positive and HBeAg-negative CHB.

• Biomedical Science Letters
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• v.11 no.3
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• pp.417-420
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• 2005

To investigate the anti-obesitic effect of FD extract which consisted of Mori radicis Cortex, Hoelen, Pueraria radix, Schizonepetae spica, Carthami Flos, Bupleuri radix and Saposhnikoviae radix in high-fat diet-fed female lean Zucker rats. Obesity was induced by feeding high-lipid diet contained $3\%$ corn oil and $1\%$ cholesterol for 8 weeks, in which FD extract was added to the diet for treatment group. The rats fed on the high fat diet showed increased gain of body weights, leading to enhanced feed efficiency ratio. Moreover high-fat diet induced hepatic lipid peroxidation and hyperlipemia. The body weight, food efficiency ratio and lipid peroxidation in the liver was decreased as compared with the rats fed on the high fat diet by FD extract. With all such changes, the blood biochemistry about lipid was, if anything, risen. These results suggest that FD extract was supposed to have effective ingredients for improving obesity for controlling adipose tissue.

• BMB Reports
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• v.34 no.4
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• pp.316-321
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• 2001

Dehydroascorbate (DHA) reductase (DHAR, EC 1.8.5.1) catalyzes the reduction of DHA to reduced ascorbate (AsA) using glutathione (GSH) as the electron donor in order to maintain an appropriate level of ascorbate in plant cells. To analyze the physiological role of DHAR in environmental stress adaptation, we developed transgenic tobacco (Nicotiana tabacum cv. Xanthi) plants that express a human DHAR gene isolated from the human fetal liver cDNA library in the chloroplasts. We also investigated the DHAR activity, levels of ascorbate, and GSH. Two transgenic plants were successfully developed by Agrobacterium-mediated transformation and were confirmed by PCR and Southern blot analysis. DHAR activity and AsA content in mature leaves of transgenic plants were approximately 1.41 and 1.95 times higher than in the non-transgenic (NT) plants, respectively In addition, the content of oxidized glutathione (GSSG) in transgenic plants was approximately 2.95 times higher than in the NT plants. The ratios of AsA to DHA and GSSG to GSH were changed by overexpression of DHAR, as expected, even though the total content of ascorbate and glutathione was not significantly changed. When tobacco leaf discs were subjected to methyl viologen at $5\;{\mu}M$, $T_0$ transgenic plants showed about a 50% reduction in membrane damage compared to the NT plants.

• BMB Reports
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• v.34 no.5
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• pp.434-439
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• 2001

The effects of regular endurance exercise, or acute-exercise and rest on the levels of lipids, carnitines and carnitine palmitoyltransferase-I (CPT-I) were investigated in male Sprague-Dawley rats. The rats were exercise trained on a treadmill for 60 min per day for 60 days (long-term trained, LT), or non-trained for 59 days (NT) and exercised for 60 min on the 60th day. In NT rats, the levels of serum nonesterified carnitine (NEC), acidsoluble acylcarnitine (ASAC), and total carnitine (TONE) increased significantly during the post-exercise recovery period (PERP). In LT rats, ASAC, and TCNE, which increased right after the 60 min running session decreased to the levels of pre-exercise during the PERP. The levels of skeletal muscle ASAC in NT rats, which increased significantly by the acute-exercise, decreased to the pre-exercise levels during the PERP. However, the ASAC level in LT rats reached its peak at 4 h after running for 60 min. Liver triglyceride (TG) and total lipids (TL), which increased by the acute-exercise, decreased to the pre-exercise levels during the PERP in both NT and LT rats. CPT-I activity in NT rats increased significantly after 1 h of a 60-min exercise and slowly decreased to pre-exercise levels during the PERP. However, the CPT-I activity in LT rats, which increased significantly by the 60 min exercise, decreased slowly and reached its pre-exercise level within 8 h of the PERP. Northern blot analysis showed that the changes of CPT-I activities during the PERP coincided with changes in CPT-I mRNA levels. This study shows that both regular endurance exercise, and acute-exercise and rest, can influence differently the levels of carnitines, lipids and CPT-I in rats. The results suggest that regular endurance exercise, rather than the acute-exercise, can change effectively the distributions of carnitines, lipids and CPT-I in rats during exercise and rest.

• BMB Reports
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• v.41 no.2
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• pp.158-163
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• 2008

Hepatitis B virus X protein (HBx) is essential for hepatitis B virus infection and exerts a pleiotropic effect on various cellular machineries. HBx has been also demonstrated as an indirect transcriptional transactivator of various different viral and cellular promoters. In addition, HBx is involved in the development of various liver diseases including hepatocellular carcinoma. However the mechanism of HBx in hepatocellular carcinogenesis remains largely unknown. In this study, to identify possible new cellular proteins interacting with HBx, we carried out yeast two-hybrid assay. We obtained several possible cellular partners including VBP1, a binding factor for VHL tumor suppressor protein. The direct physical interaction between HBx and VBP1 in vitro and in vivo was confirmed by immunoprecipitation assay. In addition, we found that VBP1 facilitates HBx-induced $NF{\kappa}B$ activation and cell proliferation. These results implicate the important role of HBx in the development of hepatocellular carcinoma through its interaction with VBP1.

• Asian-Australasian Journal of Animal Sciences
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• v.1 no.2
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• pp.89-98
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• 1988

Three experiments were conducted to determine whether cobalt (Co) or nickel (Ni) could prevent zinc (Zn) deficiency signs in pigs fed a high calcium (Ca) corn-soybean diet. The basal diet contained 1.3% Ca, .93% phytic acid and means of 34 to 48 ppm Zn. After weanling, pigs in experiment I were fed the basal diet for 9 weeks, and was found that 50 ppm Co or Ni for 5 weeks increased average daily weight gain (ADG) and reversed skin lesions toward normal. These effects were similar to those of 100 ppm supplemental Zn. The Zn content and alkaline phosphatase activity of serum from pigs supplemented with Co or Ni were higher at 2 weeks and 4 weeks (P<.05) than those of the basal group. Zn content of bone, liver and kidney, and alkaline phosphatase activity in bone were increase after 5 weeks of supplementation with Co or Ni. In experiments 2 and 3, addition of 54 ppm and 27 ppm of either Co or Ni increased (P<.05) ADG and decreased incidence of skin lesions except in one group supplemented with 27 ppm Ni. Supplemental Co or Ni increased Zn in serum and alkaline phosphatase activity in serum and bone in both experiments. Over all experiments, supplemental Co or Ni decreased Zn deficiency signs in the following order of effectiveness: 54 ppm Co, 54 ppm Ni, 27 ppm Co and 27 ppm Ni. The alleviation of signs of Zn deficiency by Co or Ni may have been the result of increased availability of dietary Zn.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.8
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• pp.3559-3563
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• 2015

The aim of the present study was to evaluate the relative contribution of CYP1A2 isoforms (-3860 G/A, -2467T/delT and -163C/A) in control subjects and breast cancer patients to the metabolism of caffeine in human liver. Restriction fragment length polymorphism analysis of PCR-amplified Fragments (PCR-RFLP) was used for the genotyping of CYP1A2 SNPs and HPLC allowed the phenotyping through the measurement of CYP1A2 activity using the 17X + 13X + 37X/137X urinary metabolite ratio (CMR) and plasma caffeine half life (T1/2). The CYP1A2 -3860A genotype was associated with a decreased risk of breast cancer. In contrast, distributions of the CYP1A2 -2467T/delT or -2467delT/delT and -163A/C or A/A genotypes among breast cancer patients and controls were similar. When the genotype and phenotype relationship was measured by comparing the mean CMR ratios and caffeine half life within the genotype groups between subjects and breast cancer patients, there were no significant differences except for -3860 A, most of them being homozygous for the -3860 G/G SNP and had a significant higher mean CMR ratio and half life than those with -3860 G/A (P=0.02). The results of this preliminary study show a significant association between CP1A2 -3860 G variant and CYP1A2 phenotype which must be confirmed by further large-size case-control studies.