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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.

Dichloroacetate Inhibits the Proliferation of a Human Anaplastic Thyroid Cancer Cell Line via a p53-independent Pathway (Dichloroacetate의 p53 비의존적 경로를 통한 인간 역분화 갑상선 암세포주의 성장억제 효과)

  • KC, Yam Bahadur;Poudel, Sunil;Jeon, Eon Ju;Shon, Ho Sang;Byun, Sung June;Jeoung, Nam Ho
    • Journal of Life Science
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    • v.28 no.12
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    • pp.1469-1476
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    • 2018
  • Occurrence of the Warburg effect in solid tumors causes resistance to cancer chemotherapy, and targeting energy metabolisms such as aerobic glycolysis is a potential strategy for alternative treatment. Dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase (PDK), shifts glucose metabolism from aerobic glycolysis to oxidative phosphorylation (OxPhos) in many cancers. In this study, we investigated the anticancer effect of DCA on a human anaplastic thyroid cancer (ATC) cell line, 8505C. We found that DCA selectively inhibits cell proliferation of the 8505C line but not of a normal thyroid line. In 8505C, the cell cycle was arrested at the G1/S phase with DCA treatment as a result of decreased antiapoptotic proteins such as $HIF1{\alpha}$, PDK1, and Bcl-2 and increased proapoptotic proteins such as Bax and p21. DCA treatment enhanced the production of reactive oxygen species which consequently induced cell cycle arrest and apoptosis. Interestingly, DCA treatment not only reduced lactate production but also increased the expression of sodium-iodine symporter, indicating that it restores the OxPhos of glucose metabolism and the iodine metabolism of the ATC. Taken together, our findings suggest that PDK inhibitors such as DCA could be useful anticancer drugs for the treatment of ATC and may also be helpful in combination with chemotherapy and radiotherapy.

U-phosphate biomineralization induced by Bacillus sp. dw-2 in the presence of organic acids

  • Tu, Hong;Yuan, Guoyuan;Zhao, Changsong;Liu, Jun;Li, Feize;Yang, Jijun;Liao, Jiali;Yang, Yuanyou;Liu, Ning
    • Nuclear Engineering and Technology
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    • v.51 no.5
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    • pp.1322-1332
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    • 2019
  • In this paper, we systematically investigated the influence of some selected ligands on the U-phosphate precipitation induced by soil bacteria. These organics are widely ranging from acetate, lactate, salicylate and citrate to oxalate. The results revealed that uranium could be biomineralized on bacteria as $UO_2HPO_4{\cdot}4H_2O$ or $(UO_2)_3(PO_4)_2{\cdot}4H_2O$. The influence of organic ligands on the biomineralization had clear-cut correlations with its complexation abilities to uranyl. It was clearly found that the U-phosphate biomineralization was affected noticeably by the strong ligands (oxalate and citrate). Further study discovered that when the organic ligands were uncompetitive with biotic $PO_4^{3-}$ for uranyl, the transformation of uranyl species from ${\beta}-UO_2(OH)_2$ colloidal particles to free $UO_2^{2+}$-ligands ions could facilitate the U-phosphate biomineralization. However, when the organic ligands competed with biotic $PO_4^{3-}$ for uranyl, the U-phosphate biomineralization were inhibited. Our results highlight the importance of complex interactions of strong organic ligands with uranyl during the bacterial precipitation of U-P compounds and thus for the mobilization and immobilization of radio-nuclides in the nature.

Protective Effect of Agrimonia pilosa var. Extract on Cultured NIH3T3 Fibroblasts Damaged by Potassium Dichromate (크롬염으로 손상된 배양 NIH3T3 섬유모세포에 대한 짚신나물 추출물의 보호 효과)

  • Lee, Jun-Hee;Seo, Young Mi
    • Korean Journal of Clinical Laboratory Science
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    • v.51 no.2
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    • pp.205-213
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    • 2019
  • The protective effect of Agrimonia pilosa var. (AP) extract on potassium dichromate ($K_2Cr_2O_7$)-induced cytotoxicity in cultured NIH3T3 fibroblasts, was examined by performing an XTT assay for the cell viability and antioxidative effects, such as lactate dehydrogenase (LDH) activity and superoxide anion-radical (SAR) scavenging activity. In this study, $K_2Cr_2O_7$ decreased the cell viability significantly in a dose-dependent manner, and the $XTT_{50}$ value was determined to be $37.5{\mu}M$, which was highly-toxic according to the Borenfreund and Puerner' toxic criteria. The antioxidant, butylated hydroxytoluene (BHT), increased remarkably the cell viability damaged by $K_2Cr_2O_7$-induced cytotoxicity in these cultures. With regard to the protective effect of the AP extract on $K_2Cr_2O_7$-induced cytotoxicity, AP extract produced a significant increase in cell viability and antioxidative effects as the inhibitory ability LDH and SAR scavenging ability. These findings suggest that oxidative stress is involved in the cytotoxicity of $K_2Cr_2O_7$, and the AP extract effectively protected the cells from $K_2Cr_2O_7$-induced cytotoxicity by antioxidative effects. These results suggest that natural resources, such as AP extract, may be a putative therapeutic agent for the diminution or treatment of cytotoxicity induced by heavy metallic bases, such as $K_2Cr_2O_7$ correlated with 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.

Cellular-protective effects of Nardotidis seu Sulculii Concha Extract against oxidative stress (산화적 스트레스에 대한 석결명의 세포 보호 효과)

  • Kim, Kwang Yeon;Lee, Seung Jin;Jee, Seon Young;Bae, Su Jin;Song, Yu Rim;Yun, Un-Jung;Bak, Seonbeen;Song, Jong Kuk;Son, Tae Jin;Son, Jae-Dong;Kim, Woo Hyun;Yang, Ju Hye;Park, Sun Dong;Kim, Sang Chan;Kim, Young Woo;Park, Kwang-Il
    • Herbal Formula Science
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    • v.29 no.2
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    • pp.71-80
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    • 2021
  • Objectives : This study investigated cellular-protective effects of Nardotidis seu Sulculii Concha water extract (NSCE) against oxidative stress induced by arachidonic acid (AA)+iron or tert-butylhydroperoxide (tBHP). Methods : In vitro, MTT assay was assessed for cell viability, and immunoblotting analysis was performed to detect expression of AMP-activated kinase (AMPK) signaling pathway and autophagy related proteins. In vivo, mice were orally administrated with the aqueous extract of NSCE of 500 mg/kg for 3 days, and then injected with CCl4 0.5 mg/kg body weight to induce acute damage. The level of liver damage was measured by serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) analysis. Results : Treatment with NSCE inhibited cell death induced by AA+iron and tBHP. NSCE induced the phosphorylation of AMPK, and this compound also induced the phosphorylation of LKB1, an upstream kinase of AMPK, and Acetyl-CoA carboxylase (ACC), a primary downstream target of AMPK. NSCE increased the protein levels of autophagic markers (LC3II and beclin-1) and decreased the phosphorylation of mammalian target of rapamycin (mTOR) and simultaneously increased the phosphorylation of unc-51-like kinase-1 (ULK-1) in time-dependent manner. Conclusions : NSCE has the ability 1) to protect cells against oxidative stress induced by AA+iron or tBHP. NSCE 2) to activate AMP-activated protein kinase (AMPK), and 3) to regulate autophagy, an important regulator in cell survival.

Butyrate Ameliorates Lipopolysaccharide-induced Myopathy through Inhibition of JNK Pathway and Improvement of Mitochondrial Function in C2C12 Cells (C2C12 세포에서 lipopolysaccharide에 의해 유도된 근육위축증에 대한 butyrate의 개선효과: JNK 신호전달 억제와 미토콘드리아의 기능 개선)

  • Pramod, Bahadur KC;Kang, Bong Seok;Jeoung, Nam Ho
    • Journal of Life Science
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    • v.31 no.5
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    • pp.464-474
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    • 2021
  • Inflammation induced by metabolic syndromes, cancers, injuries, and sepsis can alter cellular metabolism by reducing mitochondrial function via oxidative stress, thereby resulting in neuropathy and muscle atrophy. In this study, we investigated whether butyrate, a short chain fatty acid produced by gut microbiota, could prevent mitochondrial dysfunction and muscle atrophy induced by lipopolysaccharide (LPS) in the C2C12 cell line. LPS-activated MAPK signaling pathways increased the levels of the mitochondrial fission signal, p-DRP1 (Ser616), and the muscle atrophy marker, atrogin 1. Interestingly, butyrate significantly inhibited the phosphorylation of JNK and p38 and reduced the atrogin 1 level in LPS-treated C2C12 cells while increasing the phosphorylation of DRP1 (Ser637) and levels of mitofusin2, which are both mitochondrial fusion markers. Next, we investigated the effect of MAPK inhibitors, finding that butyrate had the same effect as JNK inhibition in C2C12 cells. Also, butyrate inhibited the LPS-induced expression of pyruvate dehydrogenase kinase 4 (PDK4), resulting in decreased PDHE1α phosphorylation and lactate production, suggesting that butyrate shifted glucose metabolism from aerobic glycolysis to oxidative phosphorylation. Finally, we found that these effects of butyrate on LPS-induced mitochondrial dysfunction were caused by its antioxidant effects. Thus, our findings demonstrate that butyrate prevents LPS-induced muscle atrophy by improving mitochondrial dynamics and metabolic stress via the inhibition of JNK phosphorylation. Consequently, butyrate could be used to improve LPS-induced mitochondrial dysfunction and myopathy in sepsis.

Analysis of social factors influencing authenticity of suicide for patient who attempt to suicide in emergency department: Retrospective study based Post-suicidal Care Program data (응급실로 내원한 약물중독 자살시도자의 자살 진정성에 미치는 사회적 요인 분석: 응급실 기반 자살 시도자 관리시스템 자료를 이용한 후향적 연구)

  • Ji, Jae-Gu;Kim, Yang-Weon;Kang, Ji-Hun;Jang, Yun-Deok
    • Journal of The Korean Society of Clinical Toxicology
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    • v.19 no.1
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    • pp.8-16
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    • 2021
  • Purpose: This study was conducted to analyze the social factors influencing the 'authenticity of suicidal ideation' based post-suicidal care programs in emergency departments (EDs). Methods: This retrospective study was an analysis using the data of patients who had attempted suicide and visited the ED in tertiary urban hospitals from January 1, 2016, to December 31, 2018. The variables examined included gender, age, history of previous psychiatric disease, suicide method, and the number of previous attempts. Univariate and multivariate logistic regression analyses were conducted to identify factors influencing the registration rate for the community-based post-suicide care program. Results: Overall,1,460 suicides were analyzed, 177 (1.16%) showed a high authenticity of suicide. The social factors influencing the authenticity of suicide intent were the unmarried status of men and women, joblessness, history of mental illnesses, more than two previous suicide attempts, the influence of alcohol, and an attempt to commit suicide after midnight more specifically between 24:00 to 6:00 hours in the morning (p<.05). The factors influencing the severity of the condition of high authenticity suicide patients were low Glasgow coma scores (12 points or less), lactate levels, and oxygen saturation observed in the patients who were admitted to the intensive care unit for treatment and died (p<.05). Conclusion: The need for evidence-based preventive measures and early assessment tools at the emergency medicine level is emphasized to reduce the rate of suicide attempts. If the results of this study are used in the management of suicide prevention, the evaluation of the authenticity of suicide intent will be more likely to be made at the emergency medicine level, allowing the severity to be assessed earlier.

Hepatoprotective effect of fermented Chrysanthemum indicum L. water extract on ethanol-induced liver injury in HepG2 cells (감국 발효 열수 추출물의 에탄올에 의해 손상된 HepG2 세포의 간보호 효과)

  • Seo, Tae-Su;Han, Joon-Hee;Hong, Min;Choi, Da-Hye;Lee, Deug-Chan;Yu, Keun-Hyung
    • Korean Journal of Food Science and Technology
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    • v.53 no.3
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    • pp.260-266
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    • 2021
  • This study aimed to identify the hepatoprotective effects of a fermented Chrysanthemum indicum L. water extract. The extraction yield, antioxidant activities (ABTS and DPPH), and content of luteolin and luteolin-7-glucoside were significantly higher in the fermented C. indicum L. water extract (FCI) than in the C. indicum L. water extract. Treatment with FCI (200 ㎍/mL) significantly reduced the activities of gamma(γ)-glutamyl transferase, aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase in HepG2 cells treated with 3% ethanol. Furthermore, FCI did not affect the viability of the HepG2 cells. These results suggest that FCI can be useful for the development of an effective hepatoprotective agent.

Comparison of Blood Gas, Biochemical Factors, and Hormone Concentrations, and Muscle Stress Response Factors of Chickens in General Farms and Animal Welfare Farms (일반농장과 동물복지농장 닭의 혈액 내 gas, 생화학인자, 호르몬 농도 및 근육 내 스트레스 반응인자 비교)

  • Kim, Hee-Eun;Park, Jin-Ryong;Lee, Jeong-Eun;Kang, Da-Rae;Jang, Ae-Ra;Choe, Ho-Sung;Shim, Kwan-Seob
    • Korean Journal of Organic Agriculture
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    • v.29 no.3
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    • pp.415-427
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    • 2021
  • It is generally recognized that high stocking density can increase the risk of immune dysfunction and reduction in productivity cause of elevated stress in broiler farm. The domestic livestock industry is implementing a certification system for animal welfare and livestock farms to reduce the problem of dense breeding. This study compared broiler from the general farm and animal welfare farm to confirm the effectiveness of animal welfare farms against stress. Gas concentrations in a farm of general and animal welfare farms were analyzed, blood (n=10) of the 28-day-old broiler was collected, the partial pressure of the gas in the blood was analyzed using whole blood, and biochemical factors and hormones were analyzed using the serum. Glycogen and L-lactate are analyzed using ELISA kit on finely pulverized muscles (n=10). CO2 and NH3 levels in the farm were significantly higher in general farm. Partial carbon dioxide tension (PCO2) in blood was significantly higher and partial oxygen tension (PO2) was significantly lower in the general farm. Creatinine (CREA), glucose (GLU), aspartateaminotransferase (AST), and creatinekinase (CK) in the blood were significantly higher in the general farm, and total protein (TP) and globulin (GLOB) were significantly higher in animal welfare farm. Blood corticosterone and norepinephrine were significantly higher in general farm and epinephrine was significantly higher in animal welfare farm. These results imply that animal welfare farm provides a stress-reduced breeding environment.