• Title/Summary/Keyword: dose toxicity

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Efficacy of First-Line Targeted Therapy in Real-World Korean Patients with Metastatic Renal Cell Carcinoma: Focus on Sunitinib and Pazopanib

  • Kim, Myung Soo;Chung, Ho Seok;Hwang, Eu Chang;Jung, Seung Il;Kwon, Dong Deuk;Hwang, Jun Eul;Bae, Woo Kyun;Park, Jae Young;Jeong, Chang Wook;Kwak, Cheol;Song, Cheryn;Seo, Seong Il;Byun, Seok-Soo;Hong, Sung-Hoo;Chung, Jinsoo
    • Journal of Korean Medical Science
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    • v.33 no.51
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    • pp.325.1-325.10
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    • 2018
  • Background: To evaluate survival outcomes and prognostic factors for overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC) who received sunitinib (SU) and pazopanib (PZ) as first-line therapy in real-world Korean clinical practice. Methods: Data of 554 patients with mRCC who received SU or PZ at eight institutions between 2012 and 2016 were retrospectively reviewed. Based on the targeted therapy, the patients were divided into SU (n = 293) or PZ (n = 261) groups, and the clinicopathological variables and survival rates of the two groups were compared. A multivariable Cox proportional hazard model was used to determine the prognostic factors for OS. Results: The median follow-up was 16.4 months (interquartile range, 8.3-31.3). Patients in the PZ group were older, and no significant difference was observed in the performance status (PS) between the two groups. In the SU group, the dose reduction rate was higher and the incidence of grade 3 toxicity was more frequent. The objective response rates were comparable between the two groups (SU, 32.1% vs. PZ, 36.4%). OS did not differ significantly between the two groups (SU, 36.5 months vs. PZ, 40.2 months; log-rank, P = 0.955). Body mass index, Eastern Cooperative Oncology Group PS > 2, synchronous metastasis, poor Heng risk criteria, and liver and bone metastases were associated with a shorter OS. Conclusion: Our real-world data of Korean patients with mRCC suggested that SU and PZ had similar efficacies as first-line therapy for mRCC. However, PZ was better tolerated than SU in Korean patients.

Protective Effects of Lespedeza bicolor Extract on B16/F10 Melanoma Cell Lines Damaged by Lead Acetate, Heavy Metal Compounds (중금속 화합물인 초산납으로 손상된 B16/F10 멜라닌세포주에 대한 싸리나무 추출물의 보호 효과)

  • Seo, Young-Mi
    • Korean Journal of Clinical Laboratory Science
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    • v.53 no.4
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    • pp.363-370
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    • 2021
  • This study was conducted to evaluate the dermal cytotoxicity of lead acetate (LA) and other heavy metal compounds, and the protective effect of Lespedeza bicolor (LB) extract on LA-induced cytotoxicity in cultured B16-/F10 melanoma cells. The study evaluated the antioxidative effects of LB due to its electron-donating ability (EDA), inhibitory effects on melanization and improving cell viability. LA significantly decreased cell viability in a dose-dependent manner, and the XTT50 value was determined at 52.7 µM in the studied cultures. Based on the Borenfreund and Puerner's toxicity criteria, LA was estimated to be highly cytotoxic. LA-induced cytotoxicity and cell damage was reversed by the antioxidant activity of kaempferol (KAE), thereby remarkably improving cell viability. A study of the protective effects of the LB extract on LA-induced cytotoxicity showed that the LB extract remarkably increased cell viability in the LA-treated group, and also inhibited the EDA and the total amount of melanin. The above results suggest oxidative stress-mediated cytotoxicity of LA. In the study, LB extract effectively prevented LA-induced cytotoxicity via its antioxidative activity and inhibition of melanization. In conclusion, natural resources like LB extracts may be useful agents for the prevention of oxidative stress-mediated cytotoxicity and melanization by heavy metallic compounds such as LA.

A Study on Anti-oxidant and Anti-wrinkle Effect of Supercritical Fluid Extraction of Black Carrot as a Functional Cosmetic Material (기능성화장품소재로서 자색당근 초임계추출물의 항산화 및 항주름 효능 연구)

  • Kim, Ji-Su;Lee, Ji-An
    • Journal of Convergence for Information Technology
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    • v.11 no.12
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    • pp.236-243
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    • 2021
  • The aim of this study was to evaluate the anti-oxidant and anti-wrinkle effect of the black carrot(BC) extracted by supercritical dioxide(SC-CO2). DPPH/ABTS radical scavenging and total polyphenol contents were measured to investigate the anti-oxidant activity of the BC supercritical extract. Collagen production and MMP-1 expression were assessed in normal human dermal fibroblasts(NHDF) for anti-wrinkle activity, The black carrot extract showed the highest total phenolic content(9.037±1.123 mg GAE/g extract) and the best antioxidant properties as shown by DPPH and ABTS assay. The supercritical fluid extracts of black carrot exhibited low toxicity to NHDF cells. In addition, the supercritical fluid extracts showed MMP-1 inhibition and type I pro-collagen synthesis inducing activities in a dose-dependent manner, respectively. Therefore, these results suggest that the black carrot is a potential source of high anti-oxidative, solvent-free and anti-aging material with promising applications in cosmetic, food, and beauty-food industries.

Hepatotoxicity and nephrotoxicity of saponin-enriched extract of Asparagus cochinchinensis in ICR mice

  • Sung, Ji Eun;Choi, Jun Young;Kim, Ji Eun;Lee, Hyun Ah;Yun, Woo Bin;Park, Jin Ju;Kim, Hye Ryeong;Song, Bo Ram;Kim, Dong Seob;Lee, Chung Yeoul;Lee, Hee Seob;Lim, Yong;Hwang, Dae Youn
    • Laboraroty Animal Research
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    • v.33 no.2
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    • pp.57-67
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    • 2017
  • The inhibitory effects of Asparagus cochinchinensis against inflammatory response induced by lipopolysaccharide (LPS), substance P and phthalic anhydride (PA) treatment were recently reported for some cell lines and animal models. To evaluate the hepatotoxicity and nephrotoxicity of A. cochinchinensis toward the livers and kidneys of ICR mice, alterations in related markers including body weight, organ weight, urine composition, liver pathology and kidney pathology were analyzed in male and female ICR mice after oral administration of 150, 300 and 600 mg/kg body weight/day saponin-enriched extract of A. cochinchinensis (SEAC) for 14 days. The saponin, total flavonoid and total phenol levels were found to be 57.2, 88.5 and 102.1 mg/g in SEAC, respectively, and the scavenging activity of SEAC gradually increased in a dose-dependent manner. Moreover, body and organ weight, clinical phenotypes, urine parameters and mice mortality did not differ between the vehicle and SEAC treated group. Furthermore, no significant alterations were measured in alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), blood urea nitrogen (BUN) and the serum creatinine (Cr) in the SEAC treated group relative to the vehicle treated group. Moreover, the specific pathological features induced by most toxic compounds were not observed upon liver and kidney histological analysis. Overall, the results of the present study suggest that SEAC does not induce any specific toxicity in the livers and kidneys of male and female ICR mice at doses of 600 mg/kg body weight/day.

Antioxidant and tyrosinase inhibitory activity of white beech mushroom (Hypsizygus marmoreus) extracts (흰색 느티만가닥버섯 추출물의 항산화 활성 및 tyrosinase 저해 효과)

  • Kim, Su Cheol;Kim, Hye Soo;Cho, Soo Jeong
    • Journal of Mushroom
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    • v.16 no.4
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    • pp.324-330
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    • 2018
  • The objective of this study was to evaluate antioxidant effect and tyrosinase inhibitory activity of white beech mushroom (Hypsizygus marmoreus) extracts. The white beech mushroom was extracted into hot water and methanol. Total polyphenol content was highest in the hot water extract ($8.4{\pm}3.27mg\;GAE/g$) compared to the methanol extract ($7.3{\pm}2.85mg\;GAE/g$). The flavonoids contents in hot water and methanol extracts were $3.8{\pm}3.81ug/mg$ and $2.5{\pm}1.95ug/mg$, respectively. The tyrosinase inhibitory activity of extract was increased in a dose dependent manner and tyrosinase inhibitory activity of extract (hot water extract, 69.72%; methanol extract, 52.67% at 40 mg/ml) was lower than those of positive control 2% arbutin (96%). The DPPH radical scavenging activity of the hot water and methanol extract was 80% and 74%, respectively. Hot water extract ($63.34{\pm}1.00uM\;TE/g$) were more effective in ORAC (oxygen radical absorbance capacity) value than methanol extract ($46.33{\pm}0.48uM\;TE/g$). The toxicity of hot water and methanol extracts was investigated using WST-1 (4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulphonate) assay on the B16BL6 melanoma cells.

Biological Effects and Mouthpart Deformity on Chironomus plumosus Exposed to Chromium and Copper (크롬(Cr)과 구리(Cu) 노출에 따른 Chironomus plumosus 깔다구의 생물학적 영향과 하순기절 기형발생)

  • Kim, Won-Seok;Park, Kiyun;Kwak, Ihn-Sil
    • Korean Journal of Ecology and Environment
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    • v.52 no.1
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    • pp.13-20
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    • 2019
  • Heavy metals resulted from the increase of human industrial activity are introduced into the environment through rainfall and wastewater, and have harmful effects on inhabitants. In this study, we investigated biological responses such as survival rate, growth rate, emergence rate and sex ratio, and morphological effects of mentum deformity in Chironomus plumosus, an indicator organism to evaluate pollutions on aquatic ecosystem. The survival rate of C. plumosus showed time- and dose-dependent decrease after chromium and copper exposures. Growth rate decreased at $4^{th}$ day after chromium exposure and significantly reduced at exposure to relatively high concentration (copper $1000mg\;L^{-1}$) for all exposure times. In addition, we observed that the emergence rate by exposure to copper $1000mg\;L^{-1}$ was significantly lower than that of the control group. The imbalance of sex ratios showed at relatively low concentrations (chromium 10 and $50mg\;L^{-1}$) with the high proportion of female and at the relative high concentration (copper $1000mg\;L^{-1}$) with the high proportion of male. Furthermore, the morphological mentum deformities of C. plumosus observed in the exposed group according to chromium and copper exposure. These results suggest that the heavy metal exposure in environment may influence biosynthetic and morphological stresses of benthic invertebrate C. plumosus, and aquatic midge C. plumosus are potential indicators for toxicity assessment of heavy metals such as chromium and copper.

Antioxidative Effect of Phrymaleptostachyavar. Asiatica HARA Extract on the Neurotoxicity of Aluminum Sulfate, Environmental Pollutant (환경오염물질인 황산알루미늄의 신경독성에 대한 파리풀 추출물의 항산화 효과)

  • Yoo, Sun-Mi;Lee, Jun-Hee
    • Korean Journal of Clinical Laboratory Science
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    • v.51 no.2
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    • pp.235-244
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    • 2019
  • This study examined the neurotoxicity of aluminum sulfate (AS), an environmental pollutant, and the protective effect of Phrymaleptostachya var. asiatica HARA (PLVAH) extract on the neurotoxicity induced by AS in the cultured C6 glioma cells. For this study, the cell viability and antioxidative effects, such as electron donating (ED) activity, lipid peroxidation (LP) activity, and superoxide anion-radical (SAR) scavenging activity, were analyzed. AS decreased the cell viability significantly in a dose-dependent manner and the $XTT_{50}$ value was measured at $120.0{\mu}M$ of AS. The neurotoxicity of AS was determined to be mid-toxic by Borenfreund and Puerner's toxic criteria. In addition, the catalase (CAT), antioxidant enzyme remarkably increased the cell viability injured by AS-induced neurotoxicity in these cultures. Regarding the protective effect of the PLVAH extract on AS-induced neurotoxicity, PLVAH extract significantly increased the ED ability, and the inhibitory ability of the LP and SAR scavenging ability. These findings suggest that oxidative stress is involved in the cytotoxicity of AS, and the PLVAH extract effectively protected against AS-induced neurotoxicity by its antioxidative effects. Natural resources, such as the PLVAH extract may be a putative therapeutic agent for the treatment of the toxicity induced by heavy metallic compounds, such as AS correlated with the oxidative stress.

Protective effects of extracts from the aerial parts of hydroponically cultured ginseng on alcohol-induced liver damage in mice and quantitative analysis of major ginsenosides (알코올성 간손상을 유발한 마우스 모델에서의 새싹인삼 지상부 추출물의 간 기능 보호효과 및 지표성분 함량분석)

  • Lee, Mi Kyoung;Jang, In-Bae;Lee, Min Ho;Lee, Dae Young
    • Journal of Applied Biological Chemistry
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    • v.63 no.4
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    • pp.413-420
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    • 2020
  • We studied the effects of the extract of aerial parts of hydroponically cultured ginseng (HGE) on alcohol-induced liver damage (AILD) in mice. AILD was induced by the oral administration of ethanol (EtOH) (25%; 5 g/kg body weight) for seven days in the study as well as EtOH-only groups. However, HGE (4 and 12 mg/kg) was orally administered (once daily for ten consecutive days) only to the study group, three days prior to the EtOH treatment. The HGE-treated group showed significantly lower levels of alanine aminotransferase and aspartate aminotransferase than the EtOH-only group. In addition, HGE administration decreased the level of serum lactate dehydrogenase, a known marker of liver damage. The effect of HGE on AILD was found to be dose dependent, and the consecutive administration of HGE showed no side effects in mice. Our study indicates that HGE treatment can potentially reduce oxidative stress and toxicity in the liver of alcohol-treated mice and that HGE can be a useful therapeutic agent for alcohol-induced hepatotoxicity. Additionally, a simple and efficient high-performance liquid chromatography-ultraviolet detection method was developed for determining the contents of four major ginsenosides in HGE. The aerial parts of hydroponically cultured ginseng were extracted using 70% fermented ethanol, and the contents of ginsenosides F5, F3, F1, and F2 in HGE were found to be 2.5, 4.4, 1.4, and 23.3 mg/g, respectively.

20(S)-ginsenoside Rh2 induces caspase-dependent promyelocytic leukemia-retinoic acid receptor A degradation in NB4 cells via Akt/Bax/caspase9 and TNF-α/caspase8 signaling cascades

  • Zhu, Sirui;Liu, Xiaoli;Xue, Mei;Li, Yu;Cai, Danhong;Wang, Shijun;Zhang, Liang
    • Journal of Ginseng Research
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    • v.45 no.2
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    • pp.295-304
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    • 2021
  • Background: Acute promyelocytic leukemia (APL) is a hematopoietic malignancy driven by promyelocytic leukemia-retinoic acid receptor A (PML-RARA) fusion gene. The therapeutic drugs currently used to treat APL have adverse effects. 20(S)-ginsenoside Rh2 (GRh2) is an anticancer medicine with high effectiveness and low toxicity. However, the underlying anticancer mechanisms of GRh2-induced PML-RARA degradation and apoptosis in human APL cell line (NB4 cells) remain unclear. Methods: Apoptosis-related indicators and PML-RARA expression were determined to investigate the effect of GRh2 on NB4 cells. Z-VAD-FMK, LY294002, and C 87, as inhibitors of caspase, and the phosphatidylinositol 3-kinase (PI3K) and tumor necrosis factor-α (TNF-α) pathways were used to clarify the relationship between GRh2-induced apoptosis and PML-RARA degradation. Results: GRh2 dose- and time-dependently decreased NB4 cell viability. GRh2-induced apoptosis, cell cycle arrest, and caspase3, caspase8, and caspase9 activation in NB4 cells after a 12-hour treatment. GRh2-induced apoptosis in NB4 cells was accompanied by massive production of reactive oxygen species, mitochondrial damage and upregulated Bax/Bcl-2 expression. GRh2 also induced PML/PML-RARA degradation, PML nuclear bodies formation, and activation of the downstream p53 pathway in NB4 cells. Z-VAD-FMK inhibited caspase activation and significantly reversed GRh2-induced apoptosis and PML-RARA degradation. GRh2 also upregulated TNF-α expression and inhibited Akt phosphorylation. LY294002, an inhibitor of the PI3K pathway, enhanced the antitumor effects of GRh2, and C 87, an inhibitor of the TNF-α pathway, reversed NB4 cell viability, and GRh2-mediated apoptosis in a caspase-8-dependent manner. Conclusion: GRh2 induced caspase-dependent PML-RARA degradation and apoptosis in NB4 cells via the Akt/Bax/caspase9 and TNF-α/caspase8 pathways.

Antioxidant effect of ethanol extract from Plantaginis Herba (차전초 에탄올 추출물의 항산화 효능)

  • Kim, Yoo-Jin;Kim, So Young;Jeong, Mi Jin;Lee, Un-Tak;Choo, Sung-Tae;Youn, Seok Na;Kim, Mi Ryeo
    • The Korea Journal of Herbology
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    • v.33 no.3
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    • pp.37-43
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    • 2018
  • Objectives : Butylated hydroxytoluene (BHT) and butylated hydroxyanisole (BHA) were well known as anti-oxidant, but they were limited to use because of toxicity. So, many studies are being done to develope natural anti-oxidant. Total phenolic and flavonoid contents along with total antioxidant capacity of the ethanolic extract of Plantaginis Herba (PH) were evaluated to explore the reliable and potential sources of novel natural antioxidants. Methods : Total polyphenol contents and total flavonoid contents in PH ethanol extract were determined by colorimetric method. And DPPH(1.1-diphenyl-2-picrylhydrazyl), ABTS(2'-azino-bis (3-ethylbenzothiazoline-6-Surfonicacid)) free radical scavenging capacity and reducing power inhibition activities of PH ethanol extract were measured at 100, 500, 1000, $5000{\mu}g/m{\ell}$ concentrations by spectrometric assay. Results : The total polyphenol contents and total flavonoid contents of the extract were 161.99 mg/g, 144.05 mg/g, respectively. Also, DPPH, ABTS free radical scavenging capacity and reducing power of PH ethanol extract in treated concentrations (100, 500, 1000, $5000{\mu}g/m{\ell}$) increased dose dependently. In particular, DPPH free radical scavenging capacity of PH ethanol extract from $500{\mu}g/m{\ell}$ was significantly increased compared to positive control (BHA). ABTS free radical scavenging capacity of PH ethanol extract from $1000{\mu}g/m{\ell}$ was significantly higher than BHA. Also, reducing power showed that PH ethanol extract from $500{\mu}g/m{\ell}$ was significantly increased compared to BHA. Conclusions : These results suggest that PH ethanol extract has effects to scavenge free radicals, thus PH has potential and applicable benefits for development of materials and products to have anti-oxidation functions.