• Restorative Dentistry and Endodontics
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• v.48 no.4
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• pp.39.1-39.23
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• 2023

Objectives: This study aimed to investigate the effectiveness of different topical/systemic agents in reducing the damage caused by bleaching gel to pulp tissue or cells. Materials and Methods: Electronic searches were performed in July 2023. In vivo and in vitro studies evaluating the effects of different topical or systemic agents on pulp inflammation or cytotoxicity after exposure to bleaching agents were included. The risk of bias was assessed. Results: Out of 1,112 articles, 27 were included. Nine animal studies evaluated remineralizing/anti-inflammatories agents in rat molars subjected to bleaching with 35%-38% hydrogen peroxide (HP). Five of these studies demonstrated a significant reduction in inflammation caused by HP when combined with bioglass or MI Paste Plus (GC America), or following KF-desensitizing or Otosporin treatment (n = 3). However, orally administered drugs did not reduce pulp inflammation (n = 4). Cytotoxicity (n = 17) was primarily assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay on human dental pulp cells and mouse dental papilla Cell-23 cells. Certain substances, including sodium ascorbate, butein, manganese chloride, and peroxidase, were found to reduce cytotoxicity, particularly when applied prior to bleaching. The risk of bias was high in animal studies and low in laboratory studies. Conclusions: Few in vivo studies have evaluated agents to reduce the damage caused by bleaching gel to pulp tissue. Within the limitations of these studies, it was found that topical agents were effective in reducing pulp inflammation in animals and cytotoxicity. Further analyses with human pulp are required to substantiate these findings.

• Radiation Oncology Journal
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• v.18 no.3
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• pp.200-204
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• 2000

Purpose : We already reported the results that aqueous extract of Korean ginseng roots showed a marked cytotoxicity. In this study, we investigated whether combined ginseng product with X-irradiation increase the cytotoxicity of tumor cells than X-irradiation or not. Materials and Methods : Fifty gram of Korean ginseng powder mixed with 1 L of distilled water was extracted with reflux flask under condition of $100^{\circ}C$ for 5 hrs. This aquaous ginseng extract was filtered, centrifuged and then was freezed under condition of $-90^{\circ}C$ for 16-18 hrs. The freezing extract was dried with freeze drier, and then diluted. X-irradiation was given to tumor cells by 6 MeV linear accelerator. The cytotoxicity of ginseng in vitro was evaluated from its ability to reduce the clonogenecity of fibrosarcoma (FSa II) cells. In X-irradiation alone group, each 2, 4, 6 and 8 Gy was given to tumor cells. In X-irradiation with ginseng group, 0.2 mg/mL of ginseng extract was exposed to tumor cells for 1 hour before X-irradiation. Results : The yield for 50 g of ginseng extract which was treated with freezing drier was 3.13 g($6.3\%$). Cytotoxicity In vitro was measured as survival fraction which was judged from the curve, at ginseng concentration of 0.001, 0.01, 0.1 and 1 mg/mL were $0.89\pm0.04$, $0.86\pm0.06$, $0.73\pm0.01$ and $0.09\pm0.02$, respectively. Survival fraction at X-irradiation alone of 2, 4, 6 and 8 Gy were $0.81\pm0.07$, $0.42\pm0.08$, $0.15\pm0.02$, $0.03\pm0.01$, respectively. But, suwival fraction in combined group of X-irradiation and ginseng (0.2mg/ml) at each same radiation dose were $0.28\pm0.01$, $0.18\pm0.03$, $0.08\pm0.02$, $0.006\pm0.002$, respectively (p<0.05). Conclusion : The yield for ginseng extract which was treated with freezing drier was $6.3\%$. Cytotoxicty of Fsa 11 in combined ginseng with X-irradiation group was increased than that of X-irradition alone group, and its enhancing effect seemed to be added.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4597-4606
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• 2012

Cholangiocarcinoma (CCA) is an uncommon adenocarcinoma which arises from the epithelial cells of the bile ducts. The aim of the study was to investigate the cytotoxicity, toxicity, and anticancer activity of a crude ethanolic extract of ginger (Zingiber officinale Roscoe) against CCA. Cytotoxic activity against a CCA cell line (CL-6) was assessed by calcein-AM and Hoechst 33342 assays and anti-oxidant activity was evaluated using the DPPH assay. Investigation of apoptotic activity was performed by DNA fragmentation assay and induction of genes that may be involved in the resistance of CCA to anticancer drugs (MDR1, MRP1, MRP2, and MRP3) was examined by real-time PCR. To investigate anti-CCA activity in vivo, a total of 80 OV and nitrosamine (OV/DMN)-induced CCA hamsters were fed with the ginger extract at doses of 1000, 3000, and 5000 mg/kg body weight daily or every alternate day for 30 days. Control groups consisting of 10 hamsters for each group were fed with 5-fluorouracil (positive control) or distilled water (untreated control). Median $IC_{50}$ (concentration that inhibits cell growth by 50%) values for cytotoxicity and anti-oxidant activities of the crude ethanolic extract of ginger were 10.95, 53.15, and $27.86{\mu}g/ml$, respectively. More than ten DNA fragments were visualized and up to 7-9 fold up-regulation of MDR1 and MRP3 genes was observed following exposure to the ethanolic extract of ginger. Acute and subacute toxicity tests indicated absence of any significant toxicity at the maximum dose of 5,000 mg/kg body weight given by intragastric gavage. The survival time and survival rate of the CCA-bearing hamsters were significantly prolonged compared to the control group (median of 54 vs 17 weeks). Results from these in vitro and in vivo studies thus indicate promising anticancer activity of the crude ethanolic extract of ginger against CCA with the absence of any significant toxicity. Moreover, MDR1 and MRP3 may be involved in conferring resistance of CCA to the ginger extract.

• Journal of the Korean Chemical Society
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• v.64 no.2
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• pp.79-83
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• 2020

A novel pharmacophore with epinastine (1) and NSAID moieties (2-5) was designed by molecular hybridization approach. The hybrid compounds 6-9 were synthesized by EDCI/HOBt or HATU-mediated coupling of 1 with salicylic acid (2), mefenamic acid (3), indomethacin (4) and naproxen (5), respectively, and were assessed for their inhibitory effect against NO production in LPS-induced RAW-264.7 macrophages in vitro. The Hybrids were found to exhibit significant NO production inhibitory effects with half-maximal inhibitory concentration (IC₅₀) values ranging in between 15.96 ± 1.32 and 36.68 ± 2.53 μM and were non-cytotoxic to macrophages. Comparing the inhibition concentration (IC₅₀), cytotoxicity concentration (CC₅₀) and in vitro efficacy index (iEI), 6 (IC₅₀ = 17.97 ± 1.92 μM; iEI = 11.13) and 9 (IC₅₀ = 15.96 ± 1.32 μM; iEI = 12.53) were better suited than other hybrids as well as their parent compound. Our findings signify that hybrids 6 and 9 may serve as platforms for continued investigations for the development of more efficient anti-inflammatory agents.

• Macromolecular Research
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• v.17 no.2
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• pp.99-103
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• 2009

We evaluated the efficacy of pH-sensitive micelles, formed by methoxy poly(ethylene glycol)-b-poly($\beta$)-amino ester) (PEG-PAE), as carriers for paclitaxel (PIX), a drug currently used to treat various cancers. PTX was successful encapsulated by a film hydration method. Micelles encapsulated more than 70% of the PTX and the size of the PTX-encapsulated micelles (PTX-PM) was less than 150 nm. In vitro experiments indicated that the micelles were unstable below pH 6.5. After encapsulation of PTX within the micelles, dynamic light scattering (DLS) studies indicated that low pH had a similar demicellization effect. An in vitro release study indicated that PTX was slowly released at pH 7.4 (normal body conditions) but rapidly released under weakly acidic conditions (pH 6.0). We demonstrated the safety of micelles from in vitro cytotoxicity tests on HeLa cells and the in vivo anti-tumor activity of PTX-PM in B16F 10 tumor-bearing mice. We concluded that these pH-sensitive micelles have potential as carriers for anti-cancer drugs.

• Imaging Science in Dentistry
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• v.36 no.4
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• pp.189-198
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• 2006

Purpose: To investigate the in vitro response of MC3T3-E1 osteoblastic cells to X-ray in the presence and absence of 2 deoxy-D-glucose (2-DG) and quercetin (QCT). Materials and Methods: The MC3T3-E1 cells were cultured in an ${\alpha}-MEM$ supplemented with 5 mM 2-DG or $10{\mu}M$ QCT and then the cells were incubated for 12 h prior to irradiation with 2, 4, 6, and 8Gy using a linear accelerator (Mevaprimus, Germany) delivered at a rate of 1.5 Gy/min. At various times after the irradiation, the cells were processed for the analyses of proliferation, viability, cytotoxicity, and mineralization. Results: Exposure of the cells to X-ray inhibited the tritium incorporation, 3-(4, 5-dimethylthiazol-2yl-)-2, 5-diphenyl tetrazolium bromide (MTT)-reducing activity, and alkaline phosphatase (ALP) activity, and caused cytotoxicity and apoptosis in a dose-dependent manner of the X-ray. This effect was further apparent on day 3 and 7 after the irradiation. RA+2-DG showed the decrease of DNA content, cell viability, and increase of cytotoxicity rather than RA. ALP activity increased on day 7 and subsequently its activity dropped to a lower level. 2-DG suppressed the calcium concentration, but visual difference of number of calcified nodules between RA and RA+2-DG was not noticed. RA+QCT showed the increase of DNA content, cell viability, but decrease of cytotoxicity and subG1 stage cells in the cell cycle, and increased calcified nodules in von Kossa staining rather than the RA. ALP activity showed significant increases on day 7 and subsequently its activity dropped to a lower level. Conclusion: The results showed that the 2-DG acted as a radiosensitizing agent and QCT acted as a radiosensitizing agent respectively in the irradiated MC3T3-E1 osteoblast-like cells.

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.3
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• pp.167-174
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• 2012

Natural killer (NK) cells provide one of the initial barriers of cellular host defense against pathogens, in particular intracellular pathogens. Because bone marrow-derived hematopoietic stem cells (HSCs), lymphoid protenitors, can give rise to NK cells, NK ontogeny has been considered to be exclusively lymphoid. Here, we show that porcine c-$kit^+$ bone marrow cells (c-$kit^+$ BM cells) develop into NK cells in vitro in the presence of various cytokines [interleukin (IL)-2, IL-7, IL-15, IL-21, stem cell factor (SCF), and fms-like tyrosine kinase-3 ligand (FLT3L)]. Adding hydrocortisone (HDC) and stromal cells greatly increases the frequency of c-$kit^+$ BM cells that give rise to $CD2^+CD8^+$ NK cells. Also, intracellular levels of perforin, granzyme B, and NKG2D were determined by RT-PCR and western blotting analysis. It was found that of perforin, granzyme B, and NKG2D levels significantly were increased in cytokine-stimulated c-$kit^+$ BM cells than those of controls. And, we compared the ability of the cytotoxicity of $CD2^+CD8^+$ NK cells differentiated by cytokines from c-$kit^+$ BM cells against K562 target cells for 28 days. Cytokines-induced NK cells as effector cells were incubated with K562 cells as target in a ratio of 100 : 1 for 4 h once a week. In results, $CD2^+CD8^+$ NK cells induced by cytokines and stromal cells showed a significantly increased cytotoxicity 21 days later. Whereas, our results indicated that c-$kit^+$ BM cells not pretreated with cytokines have lower levels of cytotoxicity. Taken together, this study suggests that cytokines-induced NK cells from porcine c-$kit^+$ BM cells may be used as adoptive transfer therapy if the known obstacles to xenografting (e.g. immune and non-immune problems) were overcome in the future.

• The Korea Journal of Herbology
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• v.36 no.3
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• pp.15-24
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• 2021

Objectives : The Glycyrrhiza new varieties, WONGAM and SINWONGAM, were developed through interspecific cross between Glycyrrhiza glabra and Glycyrrhiza uralensis by the National Institute of Horticultural and Herbal Science, Rural Development Administration in Korea. This in vitro study was undertaken to compare the antioxidant and cytotoxic effects between Glycyrrhiza new varieties (WONGAM and SINWONGAM) and official compendia (Glycyrrhiza glabra and Glycyrrhiza uralensis). Methods : Antioxidant activity was determined by DPPH (1,1-diphenyl-2-picrylhy drazyl), ABTS (2,2-azino-bis (3-rthylbenz-thiazoline-6-sulfonic acid)) diammonium salt, Nitrite radical scavenging assay, and Reducing Power assay. Cytotoxicity was determined by MTT assay and cell morphology was observed by an inverted microscope. Results : The DPPH, ABTS, Nitrite radical scavenging activities and reducing power of Glycyrrhiza glabra, Glycyrrhiza uralensis, WONGAM, and SINWONGAM were evaluated at different concentrations (0, 10, 50, 100, 500, 1000 ㎍/㎖). Glycyrrhiza glabra, Glycyrrhiza uralensis, WONGAM, and SINWONGAM showed similar dose-dependent increase in antioxidant activities. The cytotoxic effects with increasing doses of Glycyrrhiza new varieties and official compendia did not differ in HCT116, HT29, A549, MDA-MB231, PC3, ACHN, and HeLa cells. However, significant difference in cytotoxicity were observed in AGS, MCF7 and Hep3B cells by Glycyrrhiza glabra, Glycyrrhiza uralensis, WONGAM, and SINWONGAM. Conclusions : These results showed that Glycyrrhiza new varieties and official compendia acts as a potent antioxidant. Also, the finding that equivalent cytotoxic potency was observed in a cell dependent manner. Our study suggests that Glycyrrhiza new varieties may offer a wide-variety of health benefits.

• Journal of Life Science
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• v.26 no.1
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• pp.109-116
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• 2016

Ulmi cortex is the elm bark or root bark of Ulmus macrocarpa Hance and has been used as an ingredient of traditional medicine for anti-inflammatory, analgesic, anti-cancer and wound healing on both the East and the West. This study investigated whether the Ulmus macrocarpa Hance Water extract (UMWE) has the in vivo and in vitro immune activating effect. Animals were orally administrated for 14 days as follows: no treat group with distilled water, cyclophosphamide (CY) group with 120 mg/kg of CY, UMWE 100+CY group with 100 mg/kg of UMWE and 120 mg/kg of CY, UMWE 200+CY group with 200 mg/kg of UMWE and 120 mg/kg of CY, UMWE 100 group with 100 mg/kg of UMWE and UMWE 200 group with 200 mg/kg of UMWE. The immunosuppressive drug CY was intraperitoneally injected to induce immune suppression. Spleen indices showed small changes in CY injected groups but splenocyte indices showed greater decrease in the same groups. However, UMWE appeared to relieve CY’s immunosuppression. UMWE also delayed in vitro splenocyte death increasing its longevity. These data obtained by MTT assay and 7-amino-actinomycin D which stains preferentially dead than live cells. UMWE alone did not show cytotoxicity based on its apoptototic effect on splenocytes in vitro and in vivo. Splenic NK cell activity was maintained by UMWE under the presence of CY in vitro. The data indicated that UMWE protects splenocytes from the immunosuppressive drug CY under in vitro and in vivo conditions.

• Toxicological Research
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• v.17 no.4
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• pp.249-253
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• 2001

Fumonisin B1, a mycotoxin, is thought to induce esophageal cancer in humans and apoptosis in animal cells by inhibiting ceramide synthase. Dumonisin Bl may also generate reactive oxygen species directly or indirectly, leading to DNA damage and lipid peroxidation. In this study, a DNA fragmentation assay, dichlorofluorescein (DCF) analysis, and single cell gel electrophoresis (SCGE) were used to investigate the involvement of cellular free radicals, specifically hydrogen peroxide, in the DNA damaging activity of fumonisin B1. From an in vitro DNA fragmentation assay, E. coli DNA, damage by fumonisin Bl was increased by the addition of superxide dismutase (SOD) and decreased by catalase. SCGE and DCF analysis in vivo showed that the nuclear DNA damage and intracellular free radicals in cultured rat hepatocytes treated with fumonisin B1 were increased with the concentration of fumonisin Bl . DNA damage and free radical generation were inhibited by the addition of catalase. Fumonisin Bl , in the presence of SOD, produces hydrogen peroxide causing oxidative DNA damage and protein malfunction, leading to genotoxicity and cytotoxicity of the toxin.