• Title/Summary/Keyword: human toxicity

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Recent Research Trend on Free Radical Scavenger and Metallothioneins on Cadmium (Cadmium에 대한 Metallothionein 및 Free Radical Scavenger에 관한 최근의 연구 동향)

  • 김영숙;유대식
    • Journal of the East Asian Society of Dietary Life
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    • v.11 no.1
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    • pp.1-10
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    • 2001
  • Since the Industrial Revolution, people have enjoyed an abundant life, owing to the technological innovations of science. However, because of changes in the environment or polution to the environment, it has brought on many chronic diseases. Especially, even though it may be a small amount, if cadmium gets into a human body, because its biological half life is long, it fatally causes a kidney disease and damage to human organisms. It was reported that Metallothioneins(MT), a substance that is closely related with a free radical that comes from environmental pollution and the course of which cadmium, which causes chronic addition in the body, is formed, along with harmful metals, make the toxicity reduce. MT compound led into the body by cadmium indirectly functions as an antioxidation, supplied adequate amount of vitamin E, and suppresses the accumulation of cadmium in heart, liver and blood. Cadmium content found in Korean soil according to the test conducted from 1992 to 1996 was 0.02~0.03mg/kg in cereals, pulses, and potatoes. Free radical scavenger, finding solution for metal substance that comes from environmental pollution from food and natural substances implicates a better future for the study of food science.

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Cytotoxic Activities and Antioxidative Activities Against Liver Cancer Cell of Albizzia root (합환근의 항산화효과와 간암세포에 대한 세포독성)

  • 강병수;이갑득
    • Biomolecules & Therapeutics
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    • v.10 no.4
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    • pp.287-292
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    • 2002
  • To find new inhibitory effects from oriental drugs, Albizziae root was extracted in methanol and the extracted was stepwisely fractionated by hexane, chloroform, ethylacetate, butanol and water. In cytotoxic effect of Albizziae root fractions against cancer cell lines including human hepatoma cells(HepG2) were investigated. Expecially the butanol fraction exhibited a inhibition effects on the growth of human hepatoma cells(HepG2). It inhibited of HepG2 cells with the value of IC50. The activities of qutathione after B(a)P treatment were markedly decreased than control, but those levels were increased by the treatment of Albizziae root methanol fraction. The activity of glutathione-S-transferase after B(a)P treatment were markedly decreased than control, but those levels were increased by the treatment of Albizziae root methanol traction. Induction of phase II enzymes is a major mechanism of chemoprevention. The induction levels of quinone reductase(QR) activity in cultured murine hepatoma(Hepa IcIc7)cell by methanol extract of Albizziae root were measured. Among the tested tractions, the extracts of butanol were found to induce QR activities over 2.8 fold than control. These results suggest that Albizziae root has chemopreventive Potential by inducing QR activities and GST levels and increasing GSH

Levels of organochlorine pesticides and PCB congeners in Korean human tissues

  • Yoo, Young-Chan;Lee, Sang-Ki;Yang, Ja-Youl;Kim, Ki-Wook;Lee, Soo-Yeun;Oh, Seung-Min;Chung, Kyu-Hyuck
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.283.2-283.2
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    • 2002
  • Organochlorine pesticides and polychlorinated biphenyls (PCBs) have been used intensively in agriculture and industry for a long time. They belong to a group of contaminants whose occurrence in the environment is a serious concern to environmental chemists and toxicologists due to their resistance to degradation in the environment as well as their potential toxicity. Also. the lipophilic characteristics of these substances are responsible for their ability to bioaccumulate in tissues and organs rich in lipids of men and animals through food chain. Therefore, the measure of the levels of organochlorine pesticides and PCBs in human tissues are good markers in detemining the extent to exposure and evaluating the hazards. This study was preformed to compare concentrations of organochlorine pesticides(${\alpha}-BHC, {\beta}-BHC, {\gamma}-BHC, {\delta}-BHC$, p.p'-DDT,p.p'-DDD,p.p.'-DDE. endrin. dieldrin. aldrin) and seven marker PCBs(PCB nos. 28. 52. 101. 118. 138. 153. 180) in liver. kidney cortex, lung blood and adipose tissue collected at autopsies of 10men and 10 women using gas chromatography equipped with electron capture detector to express the data on a lipid adjusted basis. From the results, the significant differences in the levels of organochlorines of PCBs between sexes, districts where they had lived and ages were also investigated.

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Suppressive Effects of a Truncated Inhibitor K562 Protein-Derived Peptide on Two Pro-inflammatory Cytokines, IL-17 and TNF-α

  • Hwang, Jong Tae;Yu, Ji Won;Nam, Hee Jin;Song, Sun Kwang;Sung, Woo Yong;Kim, Yongae;Cho, Jang-Hee
    • Journal of Microbiology and Biotechnology
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    • v.30 no.12
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    • pp.1810-1818
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    • 2020
  • Inhibitor K562 (IK) protein was first isolated from the culture medium of K562 cells, a leukemia cell line, and is an inhibitory regulator of interferon-γ-induced major histocompatibility complex class II expression. Recently, exogenous truncated IK (tIK) protein showed potential as a therapeutic agent for inflammation-related diseases. In this study, we designed a novel putative anti-inflammatory peptide derived from tIK protein based on homology modeling of the human interleukin-10 (hIL-10) structure, and investigated whether the peptide exerted inhibitory effects against pro-inflammatory cytokines such as IL-17 and tumor necrosis factor-α (TNF-α). The peptide contains key residues involved in binding hIL-10 to the IL-10 receptor, and exerted strong inhibitory effects on IL-17 (43.8%) and TNF-α (50.7%). In addition, we used circular dichroism spectroscopy to confirm that the peptide is usually present in a random coil configuration in aqueous solution. In terms of toxicity, the peptide was found to be biologically safe. The mechanisms by which the short peptide derived from human tIK protein exerts inhibitory effects against IL-17 and TNF-α should be explored further. We also evaluated the feasibility of using this novel peptide in skincare products.

The Alcohol-inducible form of Cytochrome P450 (CYP 2E1): Role In Toxicology and Regulation of Expression

  • Novak, Raymond F.;Woodcroft, Kimberley J.
    • Archives of Pharmacal Research
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    • v.23 no.4
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    • pp.267-282
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    • 2000
  • Cytochrome P45O (CYP) 2E1 catalyzes the metabolism of a wide variety of therapeutic agents, procarcinogens, and low molecular weight solvents. CYP2E1-catalyzed metabolism may cause toxicity or DNA damage through the production of toxic metabolites, oxygen radicals, and lipid peroxidation. CYP2E1 also plays a role in the metabolism of endogenous compounds including fatty acids and ketone bodies. The regulation of CYP2E1 expression is complex, and involves transcriptional, post-transcriptional, translational, and post-translational mechanisms. CYP2E1 is transcriptionally activated in the first few hours after birth. Xenobiotic inducers elevate CYP2E1 protein levels through both increased translational efficiency and stabilization of the protein from degradation, which appears to occur primarily through ubiquitination and proteasomal degradation. CYP2E1 mRNA and protein levels are altered in response to pathophysiologic conditions by hormones including insulin, glucagon, growth hormone, and leptin, and growth factors including epidermal growth factor and hepatocyte growth factor, providing evidence that CYP2E1 expression is under tight homeostatic control.

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MS-5, a Naphthalene Derivative, Induces Apoptosis in Human Pancreatic Cancer BxPC-3 Cells by Modulating Reactive Oxygen Species

  • Suman Giri;Gyu Hwan Park;Joon-Seok Choi;Eunsook Ma;Kyung-Soo Chun;Sang Hoon Joo
    • Biomolecules & Therapeutics
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    • v.31 no.1
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    • pp.68-72
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    • 2023
  • Pancreatic cancer is one of the most fatal cancers with a poor prognosis. Standard chemotherapies have proven largely ineffective because of their toxicity and the development of resistance. Therefore, there is an urgent need to develop novel therapies. In this study, we investigated the antitumor activity of MS-5, a naphthalene derivative, on BxPC-3, a human pancreatic cancer cell line. We observed that MS-5 was cytotoxic to BxPC-3 cells, as well as inhibited the growth of cells in a concentration- and time- dependent manner. Flow cytometry analysis revealed that the percentage of annexin V-positive cells increased after MS-5 treatment. We also observed cleavage of caspases and poly (ADP-ribose) polymerase, and downregulation of Bcl-xL protein. Flow cytometry analysis of intracellular levels of reactive oxygen species (ROS) and mitochondrial superoxide suggested that MS-5 induced the generation of mitochondrial superoxide while lowering the overall intracellular ROS levels. Thus, MS-5 may be potential candidate for pancreatic cancer treatment.

Combination of oxaliplatin and β-carotene suppresses colorectal cancer by regulating cell cycle, apoptosis, and cancer stemness in vitro

  • Junghyeun Lee;Seung Chul Heo;Yuri Kim
    • Nutrition Research and Practice
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    • v.18 no.1
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    • pp.62-77
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    • 2024
  • BACKGROUND/OBJECTIVES: Colorectal cancer (CRC) is the third most common cancer worldwide with a high recurrence rate. Oxaliplatin (OXA) resistance is one of the major reasons hindering CRC therapy. β-Carotene (BC) is a provitamin A and is known to have antioxidant and anticancer effects. However, the combined effect of OXA and BC has not been investigated. Therefore, this study investigated the anticancer effects and mechanism of the combination of OXA and BC on CRC. MATERIALS/METHODS: In the present study, the effects of the combination of OXA and BC on cell viability, cell cycle arrest, and cancer stemness were investigated using HCT116, HT29, OXA-resistant cells, and human CRC organoids. RESULTS: The combination of OXA and BC enhanced apoptosis, G2/M phase cell cycle arrest, and inhibited cancer cell survival in human CRC resistant cells and CRC organoids without toxicity in normal organoids. Cancer stem cell marker expression and self-replicating capacity were suppressed by combined treatment with OXA and BC. Moreover, this combined treatment upregulated apoptosis and the stem cell-related JAK/STAT signaling pathway. CONCLUSIONS: Our results suggest a novel potential role of BC in reducing resistance to OXA, thereby enhances the anticancer effects of OXA. This enhancement is achieved through the regulation of cell cycle, apoptosis, and stemness in CRC.

Advancements in Antiviral Drug Development: Comprehensive Insights into Design Strategies and Mechanisms Targeting Key Viral Proteins

  • Wang Hangyu;Li Panpan;Shen Jie;Wang Hongyan;Wei Linmiao;Han Kangning;Shi Yichen;Wang Shuai;Wang Cheng
    • Journal of Microbiology and Biotechnology
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    • v.34 no.7
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    • pp.1376-1384
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    • 2024
  • Viral infectious diseases have always been a threat to human survival and quality of life, impeding the stability and progress of human society. As such, researchers have persistently focused on developing highly efficient, low-toxicity antiviral drugs, whether for acute or chronic infectious diseases. This article presents a comprehensive review of the design concepts behind virus-targeted drugs, examined through the lens of antiviral drug mechanisms. The intention is to provide a reference for the development of new, virus-targeted antiviral drugs and guide their clinical usage.

Cytotoxicity of Extracts and Fractions from Echinacea pupurea L. on Human Cancer Cells (Echinacea purpurea L. 추출물 및 분획물의 암세포 독성)

  • Park, Jin-Hong;Lee, Mi-Kyoung;Mun, Hyung-Chul;Choi, Geun-Pyo;Lee, Seo-Ho;Lee, Hyeon-Soo;Ryu, Lee-Ha;Lee, Gang-Yoon;Lee, Hyeon-Yong
    • Korean Journal of Medicinal Crop Science
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    • v.12 no.4
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    • pp.309-314
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    • 2004
  • The cytotoxic effects of water and ethanol extracts of Echinacea purpurea (L.) (EP) and chloroform, ethyl acetate, butanol and aqueous fractions from each extract of EP were examined. Every extract and fraction of EP inhibited the growth of human hepatocarcinoma, human gastric cancer cell, human breast cancer cells and human lung carcunoma in concentration-dependent manners over a concentration range of $0.05{\sim}1.0\;mg/ml$. Most extracts and fractions with the concentraction of 1 mg/ml showed strong inhibition of more than 70% for every cancer cell. Only aqueous fractions of each extract showed very weak inhibitons of 12 to 25% on the growth of human normal lung cell with the concentration of 1 mg/ml. Overall selectivity of the extrats and fractions on the four human cancer cell lines was over 2.5. These results indicate that EP has a very potent selective toxicity for cancer cells.

The effects GeongshinhaeGihwan 1(GGT1) has on the hGHTg (human growth hormone transgenic) obese male rats' blood-antiobestic index (형질전환 비만모델 수컷 hGHTg rats에서 경신해지환(輕身解脂丸)이 혈중 항비만지표에 미치는 영향)

  • Jung, Yang-Sam;Tsung, Pei-Chin;Choi, Seung-Bae;Kim, Gyeong -Cheol;Shin, Soon-Shik
    • Herbal Formula Science
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    • v.13 no.2
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    • pp.1-16
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    • 2005
  • Objectives: To find out the effects GGTl, an antiobestic drug widely used in clinics, has on the blood-antiobestic index and the toxicity index using the data from the hGHTg obese male rats. We looked closely into both of the two indices because GGTl antiobestic effect can happen not only by pharmacological action, but also by its toxicity. Also, we verified the difference in effect between GGTl and reductil (sibutramine), which has been approved by the FDA of the United States. Methods: After performing the experiments for 8 weeks on the hGHTg obese male rats divided into three groups: the control group, the GGTl group, and the reductil (RD) group, we anesthetized the rats with Diethyl ether and took a 3ml blood sample from the heart. Then, after coagulating the blood in room temperature by using the plasma separator, we centrifuged it for 25 minutes in 3,000rpm using the high-speed refrigerated centrifuge. We kept the separated plasma in a deep freezer at $-80^{\circ}C$, and repeatedly measured the antiobestic index and the toxicity index twice using the hematology biochemistry analyzer. Also, in order to judge the indirect toxicity index, we separated liver from kidney and observed them. Results: When we looked at the results of the analysis of covariance on the measuring elements related to the antiobestic index (TC, HDL, LDL, TG, and GLU), there was no significant difference among the groups in all measuring elements. Also, the results of the analysis of covariance on the two roups (RD group and GGTl group) showed that the p-values had no significant difference under the level of significance 0.05. When we looked at the result of the analysis of covariance on the measuring elements related to the toxicity index (GOT, GPT, GGT, CREA, UA, ALB, and TP), we could see that the p-values in GPT, ALB, and TP have a significant difference among the groups. Also, the results of the analysis of covariance about the measuring elements related to the toxicity index on both groups, RD group and GGTl group, showed no significant difference in the p-values of all of the measuring elements in the two groups, RD and GGTl group. Conclusions: In conclusion, through this experiment, the safety of GGTl has been approved, and although the verification on its medical effect has not been clearly approved, when we consider the fact that it belongs to the same group as reductil, an antiobestic drug approved by the FDA of the United States, we could indirectly verify that GGTl has an antiobestic effect. We believe that when doing a sample design for a future experiment, it needs to be performed on a greater sample size based on the power analysis that needs to be performed primarily in experiments, and a more accurate verification is needed through more systematic experiment plans.

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