• Archives of Pharmacal Research
• /
• 제19권1호
• /
• pp.12-17
• /
• 1996

Our previous studies demonstrate that menadione (MEN) is cytotoxic to platelets of rats by depleting glutathione (GSH). In order to clarify whether GSH has a role in protecting against menadione-induced cytotoxicity, the effect of GSH depletors as well as GSH precusors on menadione-induced cytotoxicity was investigated. Cysteine and dithiothreitol (DTT) prevent MEN-induced cytotoxicity in a dose-dependent manner, as determined by LDH leakage and change in turbidity. When platelets were treated with 1-chloro-2,4-dinitrobenzene (CDNB) and diethylmaleate (DEM), both of which deplete intracellular GSH, MEN-induced cytotoxicity was potentiated in the CDNB-treated paltelets, but not in the DEM-treated platelets. These data suggest that the GSH in platelets plays an important role in protecting against cytotoxicity induced by menadione.

• 약학회지
• /
• 제50권4호
• /
• pp.287-292
• /
• 2006

Protective effects of the water extract of Protaetia brevitarsis larva against $CCl_4-induced$ toxicity were investigated in primary cultures of adult rat hepatocytes. The extract used in these studies contained several minerals, fatty acids and amino acids. Treatment of hepatocyte cultures with the extract provided a significant protection from the increased LDH activity induced by $CCl_4$. The results demonstrated that the extract may have the protective effect against $CCl_4-induced$ toxicity in hepatocyte cultures.

• 대한약학회:학술대회논문집
• /
• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
• /
• pp.298.1-298.1
• /
• 2003

The aim of this study was to investigate the protective effect of acanthoic acid on liver injury induced by either tertiary-butyl hydroperoxide (tBH) or carbon tetrachloride in vitro and in vivo. Acanthoic acid, (-)-pimara-9(11),15-diene-19-oic acid, is a diterpene isolated from the root bark of Acanthopanax koreanum. In in vitro study, the cellular leakage of lactate dehydrogenase (LDH) with 1.5 mM tBH for 1 j, were significantly inhibited by treatment with acanthoic acid(25 and 5mg/mL). (omitted)

• 대한한방내과학회지
• /
• 제21권2호
• /
• pp.299-308
• /
• 2000

This study was performed to elucidate the effects of Gokajisilsosiho-Tang(GJST) on the lactic dehydrogenase(LDH) release, cell viability and activity, lipid peroxidation, DNA synthesis and the changes of total protein synthesis and GSH changes in vivo and in vitro in rat cultured hepatocytes from hydrogen peroxide$(H_2O_2)$-induced injury. The GJST extract had not an effect on cytotoxicity in all experimental results. The treatment of GJST extract of $160{\mu}g/ml$, $320{\mu}g/ml$ showed the significant effect to decrease LDH leakage induced by t-BHP in cultured rat hepatocytes. The higher concentration of GJST extract than $160{\mu}g/ml$, showed the inhibitory effect on decreasing cell viability induced by t-BHP. The treatment of t-BHP to rat cultured hepatocytes resulted in a concentration dependent increase in TBARS, in the presence of GJST extract the production of TBARS induced by hydrogen peroxide was inhibited concentration dependently, significantly inhibited at $80{\mu}g/ml$ of GJST extract and above. The GJST extract simutaneously present with t-BHP prevented the loss of total protein and GSH in a concentration dependent manner. These results suggested that GJST extract may play a hepatoprotective role in oxidative damage induced by hydrogen peroxide and a therapeutic potential of inhibiting liver injury.

• Asian Pacific Journal of Cancer Prevention
• /
• 제14권11호
• /
• pp.6869-6874
• /
• 2013

Background: Vascular endothelial growth factor and matrix metalloproteinases are two important factors for angiogenesis associated with breast cancer growth and progression. The present study was aimed to examine the effects of tamoxifen and tranilast drugs singly or in combination on proliferation of breast cancer cells and also to evaluate VEGF and MMP-9 expression and VEGF secretion levels. Materials and Methods: Human breast cancer cell lines, MCF-7 and MDA-MB-231, were treated with tamoxifen and/or tranilast alone or in combination and percentage cell survival and proliferative activity were evaluated using LDH leakage and MTT assays. mRNA expression and protein levels were examined by real-time RT-PCR and ELISA assay, respectively. Results: LDH and MTT assays showed that the combined treatment of tamoxifen and tranilast resulted in a significant decrease in cell viability and cell proliferation compared with tamoxifen or tranilast treatment alone, with significant decrease in VEGF mRNA and protein levels. We also found that tamoxifen as a single agent rarely increased MMP-9 expression. A decrease in MMP-9 expression was seen after treatment with tranilast alone and in the combined treatment MMP-9 mRNA level was decreased. Conclusions: This combination treatment can able to inhibit growth, proliferation and angiogenesis of breast cancer cells.

• Journal of Ginseng Research
• /
• 제36권3호
• /
• pp.248-255
• /
• 2012

Potential antioxidant effect of processed ginseng (sun ginseng, SG) on oxidative stress generated by tert-butyl hydroperoxide (t-BHP) was investigated in HepG2 cells. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and lactate dehydrogenase (LDH) leakage test demonstrated that SG dose-dependently prevents a loss of cell viability against t-BHP-induced oxidative stress. Also, SG treatment dose-dependently relieved the increment of activities of hepatic enzymes, such as aspartate aminotrasferase and alanine aminotransferase, and lipid peroxidation mediated by t-BHP treatment in HepG2 cells. SG increased the gene expression of antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase. However, high dose of SG treatment caused decrease in mRNA level of glutathione peroxidase as compared to low dosage of SG-treated cells. The gene expression of glutathione reductase was found to be slightly increased by SG treatment. In addition, SG extract attributed its hepaprotective effect by inducing the mRNA level of bcl-2 and bcl-xL but reducing that of bax. But, the gene expression of bad showed no significant change in SG-treated HepG2 cells. These findings suggest that SG has hepatoprotective effect by showing reduction of LDH release, activities of hepatic enzymes and lipid peroxidation and regulating the gene expression of antioxidant enzymes and apoptosis-related molecules against oxdative stress caused by t-BHP in HepG2 cells.

• Nutrition Research and Practice
• /
• 제11권2호
• /
• pp.97-104
• /
• 2017

BACKGROUND/OBJECTIVE: Although Angelica keiskei (AK) has widely been utilized for the purpose of general health improvement among Asian, its functionality and mechanism of action. The aim of this study was to determine the protective effect of ethanol extract of AK (AK-Ex) on acute hepatotoxicity induced by acetaminophen (AAP) in HepG2 human hepatocellular liver carcinoma cells and HepaRG human hepatic progenitor cells. MATERIALS/METHODS: AK-Ex was prepared HepG2 and HepaRG cells were cultured with various concentrations and 30 mM AAP. The protective effects of AK-Ex against AAP-induced hepatotoxicity in HepG2 and HepaRG cells were evaluated using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide, lactate dehydrogenase (LDH) assay, flow cytometry, and Western blotting. RESULTS: AK-Ex, when administered prior to AAP, increased cell growth and decreased leakage of LDH in a dose-dependent manner in HepG2 and HepaRG cells against AAP-induced hepatotoxicity. AK-Ex increased the level of Bcl-2 and decreased the levels of Bax, Bok and Bik decreased the permeability of the mitochondrial membrane in HepG2 cells intoxicated with AAP. AK-Ex decreased the cleavage of poly (ADP-ribose) polymerase (PARP) and the activation of caspase-9, -7, and -3. CONCLUSIONS: These results demonstrate that AK-Ex downregulates apoptosis via intrinsic and extrinsic pathways against AAP-induced hepatotoxicity. We suggest that AK could be a useful preventive agent against AAP-induced apoptosis in hepatocytes.

• The Korean Journal of Physiology and Pharmacology
• /
• 제21권2호
• /
• pp.189-195
• /
• 2017

This study aimed to compare the cellular toxicities of three clinically used dry eye treatments; 3% diquafosol tetrasodium and hyaluronic acid at 0.3 and 0.18%. A methyl thiazolyltetrazoiun (MTT)-based calorimetric assay was used to assess cellular proliferation and a lactate dehydrogenase (LDH) leakage assay to assess cytotoxicity, using Human corneal epithelial cells (HCECs) exposed to 3% diquafosol tetrasodium, 0.3% hyaluronic acid (HA), or 0.18% HA or 1, 6 or 24 h. Cellular morphology was evaluated by inverted phase-contrast light microscopy and electron microscopy, and wound widths were measured 24 h after confluent HCECs were scratched. Diquafosol had a significant, time-dependent, inhibitory effect on HCEC proliferation and cytotoxicity. HCECs treated with diquafosol detached more from the bottoms of dishes and damaged cells showed degenerative changes, such as, reduced numbers of microvilli, vacuole formation, and chromatin of the nuclear remnant condensed along the nuclear periphery. All significantly stimulated reepithelialization of HCECs scratched, which were less observed in diquafosol. Therefore, epithelial toxicity should be considered after long-term usage of diquafosol and in overdose cases, especially in dry eye patients with pre-existing punctated epithelial erosion.

• 대한약리학회지
• /
• 제29권2호
• /
• pp.189-193
• /
• 1993

흰쥐태 뇌간의 세포를 배양하여 glutamate에 6시간까지 노출시 glutamate의 농도 및 노출 시간에 의존적으로 세포내 5-HT 및 5-HIAA의 함량이 감소하였고, 배양액으로 LDH의 유출이 증가하였다. Tetrodotoxin은 glutamate의 작용을 차단하지 못하였다. NMDA 수용체 통로 봉쇄제인 MK-801에 의해 glutamate의 작용이 효과적으로 차단되었고, non-NMDA 길항제인 CNQX는 효과가 없었으므로, serotonin 신경세포에 대한 glutamate의 작용은 NMDA 수용체의 자극에 의한 것으로 사료된다.

• Asian Pacific Journal of Cancer Prevention
• /
• 제14권7호
• /
• pp.4267-4271
• /
• 2013

Background: As natural medicines in Asia, curcumin and triptolide extracted from different drug plants have proven to possess anticancer potential and widely used for anti-cancer research. The present study attempted to clarify that curcumin and triptolide synergistically suppress ovarian cancer cell growth in vitro. Methods: To test synergic effects, cell viability and apoptosis were analyzed after curcumin and triptolide combination treatment on ovarian cancer cell lines. Synergistic effects on apoptosis induction were determined by lactate dehydrogenase (LDH) leakage assay, intracellular reactive oxygen species (ROS) assay, mitochondrial membrane potential (MMP) loss assay and flow cytometry analysis. Critical regulators of cell proliferation and apoptosis related were analyzed by qRT-PCR and Western blotting. Results: We showed that the combination of curcumin and triptolide could synergistically inhibit ovarian cancer cell growth, and induce apoptosis, which is accompanied by HSP27 and HSP70, indicating that HSP27 and HSP70 play the important role in the synergic effect. Conclusions: From the result present here, curcumin and triptolide combination with lower concentration have a synergistic anti-tumor effect on ovarian cancer and which will have a good potential in clinical applications.