• Korean Journal of Veterinary Research
• /
• v.56 no.1
• /
• pp.15-21
• /
• 2016

NAD(P)H-quinone oxidoreductase-1 (NQO1) is a down-stream target gene of nuclear factor erythroid 2-related factor 2 (Nrf2), and performs diverse biological functions. Recently, NQO1 is recognized as an effective gene for the cytotoxic inserts with its diverse biological functions, which is focused on antioxidant properties. The aim of present study was to assess the impact of NQO1 knockdown on cytoprotection-related protein expression in cisplatin cytotoxicity by using small interfering (si) RNA targeted on NQO1 gene. Cytotoxicity of cisplatin on ACHN cells was assessed in a dose- and time-dependent manner after siScramble or siNQO1 treatment. After cisplatin treatment, cells were subjected to cell viability assay, western-blot analysis, and immunofluorescence study. The cell viability was decreased in the siNQO1 cells (50%) than the siScramble cells (70%) after 24 h of cisplatin ($20{\mu}M$) treatment. Moreover, cytoprotection-related protein expressions were markedly suppressed in the siNQO1 cells after cisplatin treatment. The expression of Nrf2 and Klotho were decreased by 20% and 40%, respectively, of that in siScramble cells. Nrf2 and Klotho activation were also decreased in cisplatin treated siNQO1 cells, confirmed by cytoplasm-tonuclear translocation. Our findings demonstrate that the increased cisplatin-induced cytotoxicity was accompanied by suppressed Nrf2 activation and Klotho expression in siNQO1 cells.

• Journal of Nutrition and Health
• /
• v.32 no.3
• /
• pp.318-326
• /
• 1999

Apoptotic cell death, characterized by DNA fragmentation and morphological changes, has previously been shown to occur in vascular endothelial cells cultured with hydrogen peroxide. The present study examined the induction of apoptosis by hydrogen peroxide and whether pyruvate, a key glycolytic intermediate and $\alpha$-keto-monocarboxylate, can inhibit the apoptotic effects in bovine pulmonary artery endothelial cells(BPAECs). Culture with 500uM hydrogen peroxide resulted in 30% cell death and induced morphological changes and DNA fragmentation. Cell injury was inhibited by the treatment with pyruvate. Pyruvate(0.1-5.0mM), and cell viability increased in a dose-dependent manner. In the presence of pyruvate(10~20mM), the viability was improved to over 95%. In contrast, treatment with lactate, a reduced form of phyuvate, did not protect against cell death oxidative stress-induced loss of viability and apoptosis was examined with $\alpha$-cyano-3-hydroxycinnarmate(COHC) as a selective mitochondrial monocarboxylate transport blocker. Incubation with COHC(500uM) did not significantly affect cell viability in the presence of hydrogen peroxide. The cytoprotection by pyruvate(3mM)against hydrogen peroxide stress was abolished by COHC. This indicates that the cytoprotection by pyruvate against oxidative stress in endothelial cells is mediated, at least in part, by mitochondrial pyruvate uptake and hence endothelial enerygetics. However, cytosolic mechanisms related, at least in part, by mitochondrial pyruvate uptake and hence endothelial energetics. However, cytosolic mechanisms related to the glutathione system may also contribute. The results suggest that pyruvate has therapeutic potential in the treatment of oxidative stress-induced cytotoxicity associated with increased apoptosis.

• Journal of Oriental Physiology
• /
• v.14 no.2 s.20
• /
• pp.1-9
• /
• 1999

Ethanol induces compoundhemorrhagic gastric lesions and causes a dose-dependent decrease in the concentration of endogenous nonprotein sulfhydryls in rat gastric mucosa. Sulfhydryl-containing drugs protect rats from ethanol - induced gastric lesions. Based on this findings, we investigated the involvement of sulfhydryl compounds in the antioxidant effects of Puerariae radix, a traditional herbal medicine, against ethanol - induced gastric lesions in the absence and presence of iodoacetamide(IDA. sulfhydryl blocking agent) in rats. respectively. Because of the known role of sulfhydryls in gastric cytoprotection, its role in gastric antioxidation was of intrest. In vitro, Puerariae radix extract(PRE) reduced linoleic acid autooxidation and exert DPPH radical scavenging effect. In vivo. PRE increased antioxidants(SOD, catalase. GSH) and reduced lipid peroxide level in ethanol-induced gastric mucosal lesions. But treatment with PRE plus IDA significantly inhibit the antioxidant effects such as SOD and GSH but did not affect catalase levels. These results suggest that Puerariae radix may play roles in the gastric cytoprotection through antioxidant effects and increase of SOD activity and GSH level are dependent of endogenous sulfhydryls.

• Proceedings of the Korean Society of Applied Pharmacology
• /
• 2002.07a
• /
• pp.220-220
• /
• 2002

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.23 no.1
• /
• pp.57-62
• /
• 2009

Smilacis Chinae Radix has been used as an anti-inflammatory agent. This study was performed to anti-inflammatory and MAP kinase signaling pathway in vitro. Experimental studies were obtained by measuring the Cytotoxicity, production of NO, PGE2, TNF-$\alpha$ and protein level of catalase, SOD, MAP kinase, The results were summarized as follows: Smilacis Chinae Radix was not cytotoxic effects against Raw264.7 and HEK293 cells. Concentration of $100{\mu}g/m{\ell}$ Smilacis Chinae Radix inhibited the production of NO in the Raw264.7 cell stimulated with LPS. All concentrations of Smilacis Chinae Radix not significantly inhibited the production of PGE2 in the Raw264.7 cell stimulated with LPS. All concentrations of Smilacis Chinae Radix did not inhibit the production of TNF-$\alpha$ in the Raw264.7 cell stimulated with LPS. Smilacis Chinae Radix has not effect of blocking NF-${\kappa}B$ into nucleus in LPS-induced macrophage Raw264.7 cell. Smilacis Chinae Radix has the effect of Cytoprotection through activation of ERK and inhibition of p38 and JNK. Accordingly the results show Smilacis Chinae Radix could induce anti-inflammation and Cytoprotection effects against In vitro, but it needs more research on the precise mechanism of such effects.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.18 no.6
• /
• pp.1805-1809
• /
• 2004

In order to validate the use of Radix Curcumae Aromaticae as an anti-inflammatory drug in the traditional Korean medicine, I have investigated the effect of water-soluble extract of Radix Curcumae Aromaticae (ECA) on the expression of inducible heme oxygenase-1 (HO-1), which ha.s anti-inflammatory and cytoprotective effects stimulates, in human umbilical vein endothelial cells (HUVECs) stimulated with a high dose of pro-inflammatory tumor necrosis factor-alpha (TNF-α). The extract protected dose-dependently HUVECs against TNF-α-induced apoptosis, as measured qualitatively by a nuclear staining method using the fluoresoence DAPI and quantitatively by a flow cytometry using fluoresce-enhanced Annexin V antibody, and significantly Increased HO-1 expression, as determined by Western blotting analysis using anti-HO-1 antibody. Biockage of HO-1 activity by a pharmacological inhibitor reversed cytoprotection afforded by the extract, and treatment with carbon monoxide, one of HO-1 metabolites, resulted in cytoprotection comparable to the extract. These results suggest that ECA may have therapeutic potential in the control of endothelial disorders caused by inflammatory cytokines.

• Journal of Nutrition and Health
• /
• v.27 no.7
• /
• pp.752-759
• /
• 1994

It is accepted that colostral macrophages have protective effects on gastrointestinal tract of the neonates. Macrophages act as a major defensive cells in colostrum and serve as a main source of colostral prostaglandins which are known to exert cytoprotection for gastrointestinal tract of neonates against infectious agents and drugs such as aspirin. This study was conducted to evaluate the total cell numbers and differential counts for macrophages, neutrophils and lymphocytes in colostrum of Korean mothers. To compare the level of PGE2, 6-keto-PGF1$\alpha$, and TXB2 between colostrum and serum of postpartum mothers, radioimmunoassay adopting eicosanoids-antibody complex method was applied instead of charcoal method. The results were as follows : 1) Total defensive cell count was 7.6$\pm$2,37$\times$106 cells/ml, differential counts of macrophages, neutrophils and lymphocytes were 57.49$\pm$4.14%, 37.98$\pm$4.43% and 4.29$\pm$0.73% respectively. 2) The order of prostaglandin level in colostrum which are known to enhance development and cytoprotection of gastrointestinal tract, was 6-keto-PGF1$\alpha$, TXB2 and PGE2. Colostral PGE2 level was 584.6$\pm$72.3 pg/ml, higher than that of serum(p<0.01). 6-keto-PGF1$\alpha$, the most abundant prostaglandin in colostrum was higher than in serum level, too (p<0.01). Serum TXB2 level of postpartum mothers(n=42) was higher nine times than that of colostrum(p<0.01), which seems to cause vasoconstriction of uterus in postpartum period. 3) In preterm mothers, serum level of TXB2 level in both groups.

• Biomolecules & Therapeutics
• /
• v.20 no.3
• /
• pp.306-312
• /
• 2012

Resveratrol (trans-3,5,4'-trihydroxystilbene) has received considerable attention recently for the potential neuroprotective effects in neurodegenerative disorders where heme oxygenase-1 (HO-1) and sirtuin 1 (SIRT1) represent promising therapeutic targets. Resveratrol has been known to increase HO-1 expression and SIRT1 activity. In this study, the effects of resveratrol and trans-3,5,4'-trimethoxystilbene (TMS), a resveratrol derivative, on cytotoxicity caused by glutamate-induced oxidative stress, HO-1 expression, and SIRT1 activation have been investigated by using murine hippocampal HT22 cells, which have been widely used as an in vitro model for investigating glutamate-induced neurotoxicity. Resveratrol protected HT22 neuronal cells from glutamate-induced cytotoxicity and increased HO-1 expression as well as SIRT1 activity in a concentration-dependent manner. Cytoprotection afforded by resveratrol was partially reversed by the specific inhibition of HO-1 expression by HO-1 small interfering RNA and the nonspecific blockage of HO-1 activity by tin protoporphyrin IX, but not by SIRT1 inhibitors. Surprisingly, TMS, a resveratrol derivative with methoxyl groups in lieu of the hydroxyl groups, and trans-stilbene, a non-hydroxylated analog, failed to protect HT22 cells from glutamate-induced cytotoxicity and to increase HO-1 expression and SIRT1 activity. Taken together, our findings suggest that the cytoprotective effect of resveratrol was at least in part associated with HO-1 expression but not with SIRT1 activation and, importantly, that the presence of hydroxyl groups on the benzene rings of resveratrol appears to be necessary for cytoprotection against glutamate-induced oxidative stress, HO-1 expression, and SIRT1 activation in HT22 neuronal cells.

• Herbal Formula Science
• /
• v.26 no.4
• /
• pp.329-340
• /
• 2018

Objectives : In Traditional Korean medicine, Daucus carota L. has been used for treating dyspepsia, diarrhea, dysentery and cough. Recent pharmacognosic evidence showed D. carota has anti-oxidant, anti-cancer, anti-fungal, and hypotensive effects. Present study investigated hepato-protective effect of D. carota ethanol extract (DCE) against oxidative stress in HepG2 cells. Methods : After HepG2 cells were pretreated with different concentrations of DCE, the cells were exposed to tert-butyl hydroperoxide (tBHP) for inducing oxidative stress. Cell viability, hydrogen peroxide production, glutathione concentration, and mitochondrial membrane potentials were measured to explore hepato-protective effect of DCE. Phosphorylation of AMP-activated protein kinase (AMPK) and effect of compound C on cell viability were determined to investigate the role of AMPK on DCE-mediated cytoprotection. Results : DCE significantly decreased the tBHP-mediated cytotoxicity in a concentration dependent manner and reduced the changes on apoptosis-related proteins by tBHP in HepG2 cells. In addition, DCE significantly prevented hydrogen peroxide production, glutathione depletion, and mitochondrial membrane impairment induced by tBHP. Treatment with DCE increased phosphorylation of AMPK, and the DCE-mediated cytoprotection was abolished by pretreatment with compound C. Conclusions : These results demonstrate that DCE can protect hepatocytes from oxidative stress through activation of AMPK.

• Archives of Pharmacal Research
• /
• v.16 no.1
• /
• pp.71-74
• /
• 1993

The protective effect of adenosine triphosphate (ATP) on gastic ulcer induced in rats has been studied. Gastic ulceration was induced by hypothemic restraint stress or dicolofenac sodium. Gastic acid secretion and mucosal injury produced by the hypothemic restraint stress was greater as compared with those produced by diclofenac sodifum. ATP significantly reduced area of injury, however, increased cyclic adenosine monophosphate (cATP) content. Administration of dipyridamole along with ATP did not change the total lesion area in both models when compared to ATP alone. Aminophyline antagonized antagonized the protective effect of ATP on the injured area. Famotidine was found to be effective in reducing gastric acid output as well as the total injured area without any change in cAMP content when given along with ATP.