• Title/Summary/Keyword: Detoxification.

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The Inhibitory Effects of the Methanolic Fraction of Pueraria Radix on Hydrogen peroxide-induced Lipid peroxidation and Cadmium-induced cytotoxicity

  • Lim, Jin-A;Kim, Yun-Ha;Lee, Jeong-Ho;Lee, In-A;Baek, Seung-Hwa
    • Proceedings of the PSK Conference
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    • 2003.10b
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    • pp.209.2-209.2
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    • 2003
  • The effects of the methanol subfraction of Pueraria radix on hydrogen peroxide-induced lipid peroxidation and Cd-induced cytotoxicity were investigated in NIH3T3 fibroblasts. After the methanol subfraction treatment, the content of MDA induced by 600${\mu}$M H2O2 significantly decreased in proportion to the subfraction concentrations as well as 50${\mu}$M CdCl2-induced cytotoxicity. Especially, 200$\mu\textrm{g}$/mg concentration of methanol subfraction was strongly shown inhibition of lipid peroxidation and detoxification of Cd. These results suggest that the methanol subfraction of Pueraria radix retains a potential antioxidant and protective effect against cadmium.

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Metallothionein gene expression in different tissues of Crucian carp (Carassius auratus) exposed to cadmium chloride

  • Park, Kwang-Sik;Bae , Hee-Kyung;Nam, Seong-Sook;Kim, En-Kyoung
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.295.1-295.1
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    • 2002
  • Metallothioneins (MTs) are a go up of heavy metal-binding proteins characterized by cystein-rich low molecular weight(6000 - 10.000 Da). They plays a major role in the detoxification of heavy metals and also in scavenging of superoxide radicals. They are known to be induced by heavy metals in various organs of different species and represent a potential biomarker of aquatic heavy metal contamination. (omitted)

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Pleiotropic Effects of Caffeine Leading to Chromosome Instability and Cytotoxicity in Eukaryotic Microorganisms

  • Chung, Woo-Hyun
    • Journal of Microbiology and Biotechnology
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    • v.31 no.2
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    • pp.171-180
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    • 2021
  • Caffeine, a methylxanthine analog of purine bases, is a compound that is largely consumed in beverages and medications for psychoactive and diuretic effects and plays many beneficial roles in neuronal stimulation and enhancement of anti-tumor immune responses by blocking adenosine receptors in higher organisms. In single-cell eukaryotes, however, caffeine somehow impairs cellular fitness by compromising cell wall integrity, inhibiting target of rapamycin (TOR) signaling and growth, and overriding cell cycle arrest caused by DNA damage. Among its multiple inhibitory targets, caffeine specifically interacts with phosphatidylinositol 3-kinase (PI3K)-related kinases causing radiosensitization and cytotoxicity via specialized intermediate molecules. Caffeine potentiates the lethality of cells in conjunction with several other stressors such as oxidants, irradiation, and various toxic compounds through largely unknown mechanisms. In this review, recent findings on caffeine effects and cellular detoxification schemes are highlighted and discussed with an emphasis on the inhibitory interactions between caffeine and its multiple targets in eukaryotic microorganisms such as budding and fission yeasts.

Molecular Basis of the KEAP1-NRF2 Signaling Pathway

  • Takafumi Suzuki;Jun Takahashi;Masayuki Yamamoto
    • Molecules and Cells
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    • v.46 no.3
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    • pp.133-141
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    • 2023
  • Transcription factor NRF2 (NF-E2-related factor 2) is a master regulator of cellular responses against environmental stresses. NRF2 induces expression of detoxification and antioxidant enzymes and suppresses inductions of pro-inflammatory cytokine genes. KEAP1 (Kelch-like ECH-associated protein 1) is an adaptor subunit of CULLIN 3 (CUL3)-based E3 ubiquitin ligase. KEAP1 regulates the activity of NRF2 and acts as a sensor for oxidative and electrophilic stresses. NRF2 has been found to be activated in many types of cancers with poor prognosis. Therapeutic strategies to control NRF2-overeactivated cancers have been considered not only by targeting cancer cells with NRF2 inhibitors or NRF2 synthetic lethal chemicals, but also by targeting host defense with NRF2 inducers. Understanding precise molecular mechanisms how the KEAP1-NRF2 system senses and regulates the cellular response is critical to overcome intractable NRF2-activated cancers.

Effects of immune-challenged domestic silkworm hemolymph on the regulation of SIRT5 and PRDx1 expression

  • Jin Ha Yun;Seong Ryul Kim;Seung-Won Park
    • International Journal of Industrial Entomology and Biomaterials
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    • v.47 no.2
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    • pp.134-139
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    • 2023
  • SIRT5 and PRDx1 play crucial roles in cancer and are involved in the basic mechanisms of reactive oxygen species detoxification. In our previous studies, we showed that hemolymph extracts of immune-challenged Bombyx mori have antioxidant properties. Following H2O2 stimulation, immune-challenged B. mori hemolymph extracts elicited SIRT5 downregulation activity, reaching effective activity at the highest concentration of 100 ppm. Additionally, cells treated with immune-challenged B. mori hemolymph extracts demonstrated increased PRDx1 mRNA expression compared to that of PBS-treated cells. Therefore, immune-challenged B. mori hemolymph extracts offer a potential auxiliary means of treating drug-resistant tumors through downregulation of SIRT5 and upregulation of PRDx1 expression. Nevertheless, further studies on the effects of B. mori hemolymph on SIRT5 and PRDx1 regulation are pertinent for using it as a food or pharmaceutical material and understanding its therapeutic effect on tumors, including those that are drug-resistant.

Potential for Efficient Synthesis of GSH Utilizing GCS1 and GLR1 Mutant Strains of Candida albicans

  • Jaeyoung SON;Min-Kyu KWAK
    • The Korean Journal of Food & Health Convergence
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    • v.10 no.2
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    • pp.7-11
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    • 2024
  • Glutathione (GSH) is a vital compound composed of glutamic acid, cysteine, and glycine, crucial for cellular functions including oxidative stress defense and detoxification. It has widespread applications in pharmaceuticals, cosmetics, and food industries due to its antioxidant properties and immune system support. Two primary methods for GSH synthesis are enzymatic and microbial fermentation. Enzymatic synthesis is efficient but costly, while microbial fermentation, particularly using yeast strains like Candida albicans, offers a cost-effective alternative. This study focuses on genetically modifying C. albicans mutants, specifically targeting glutathione reductase (GLR1) and gamma-glutamylcysteine synthetase (GCS1) genes, integral to GSH synthesis. By optimizing these mutants, the research aims to develop a model for efficient GSH production, potentially expanding its applications in the food industry.

A prognosis discovering lethal-related genes in plants for target identification and inhibitor design (식물 치사관련 유전자를 이용하는 신규 제초제 작용점 탐색 및 조절물질 개발동향)

  • Hwang, I.T.;Lee, D.H.;Choi, J.S.;Kim, T.J.;Kim, B.T.;Park, Y.S.;Cho, K.Y.
    • The Korean Journal of Pesticide Science
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    • v.5 no.3
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    • pp.1-11
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    • 2001
  • New technologies will have a large impact on the discovery of new herbicide site of action. Genomics, combinatorial chemistry, and bioinformatics help take advantage of serendipity through tile sequencing of huge numbers of genes or the synthesis of large numbers of chemical compounds. There are approximately $10^{30}\;to\;10^{50}$ possible molecules in molecular space of which only a fraction have been synthesized. Combining this potential with having access to 50,000 plant genes in the future elevates tile probability of discovering flew herbicidal site of actions. If 0.1, 1.0 or 10% of total genes in a typical plant are valid for herbicide target, a plant with 50,000 genes would provide about 50, 500, and 5,000 targets, respectively. However, only 11 herbicide targets have been identified and commercialized. The successful design of novel herbicides depends on careful consideration of a number of factors including target enzyme selections and validations, inhibitor designs, and the metabolic fates. Biochemical information can be used to identify enzymes which produce lethal phenotypes. The identification of a lethal target site is an important step to this approach. An examination of the characteristics of known targets provides of crucial insight as to the definition of a lethal target. Recently, antisense RNA suppression of an enzyme translation has been used to determine the genes required for toxicity and offers a strategy for identifying lethal target sites. After the identification of a lethal target, detailed knowledge such as the enzyme kinetics and the protein structure may be used to design potent inhibitors. Various types of inhibitors may be designed for a given enzyme. Strategies for the selection of new enzyme targets giving the desired physiological response upon partial inhibition include identification of chemical leads, lethal mutants and the use of antisense technology. Enzyme inhibitors having agrochemical utility can be categorized into six major groups: ground-state analogues, group specific reagents, affinity labels, suicide substrates, reaction intermediate analogues, and extraneous site inhibitors. In this review, examples of each category, and their advantages and disadvantages, will be discussed. The target identification and construction of a potent inhibitor, in itself, may not lead to develop an effective herbicide. The desired in vivo activity, uptake and translocation, and metabolism of the inhibitor should be studied in detail to assess the full potential of the target. Strategies for delivery of the compound to the target enzyme and avoidance of premature detoxification may include a proherbicidal approach, especially when inhibitors are highly charged or when selective detoxification or activation can be exploited. Utilization of differences in detoxification or activation between weeds and crops may lead to enhance selectivity. Without a full appreciation of each of these facets of herbicide design, the chances for success with the target or enzyme-driven approach are reduced.

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The Change of Glutathione Metabolism in Liver and Kidney of Cisplatin treated Rats (Cisplatin 투여 후 백서의 간 및 신장에서 Glutathione 대사의 변화)

  • Kim, Seong-Yong;Chung, Jae-Yong;Kim, Jae-Ryong;Kim, Jung-Hye
    • Journal of Yeungnam Medical Science
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    • v.11 no.2
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    • pp.262-269
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    • 1994
  • Glutathione (GSH) is a well-known antioxidative cellular component which is ubiquitous in nature. Several enzymes involved in GSH metabolism and recycling have been found to play important roles in detoxification of xenobiotics and free radicals. In this study, total GSH content, activity of GSH peroxidase and GSH reductase were measured in liver and kidney of cisplatin treated rats. Total GSH content (mM/g protein) of liver was higher in cisplatin treated rats ($1.51{\pm}0.28$) than of nontreated control ($0.95{\pm}0.28$), and in kidney, it was also higher in cisplatin treated rats ($0.87{\pm}0.20$) than that of control ($0.68{\pm}0.14$). The activity of GSH peroxidase (${\mu}M/mg$ protein/min) was lower in liver of cisplatin treated rats ($348.0{\pm}18.54$) than that of control ($415.5{\pm}53.15$), in kidney it was increase din cisplatin treated rats ($380.5{\pm}51.86$) compared to control ($327.3{\pm}20.36$). The activity of GSH reductase (${\mu}M/mg$ protein/min) was higher in liver of cisplatin treated rats ($3.09{\pm}0.88$) than that of control ($2.28{\pm}0.61$), in kidney it was also higher in cisplatin treated rats ($8.50{\pm}2.62$) than that of control ($3.30{\pm}1.10$). In summary, detoxification of ciplatin was revealed lesser effect in kidney as show increasion of GSH peroxidase and reductase and detoxification of cisplatin was expressed effectively in liver by increasing of GSH content and decreasing GSH peroxidase.

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Protective Effects of Enzymatic Oyster Hydrolysate on Acetaminophen-induced HepG-2 Cell Damage (아세트아미노펜 유도 HepG-2 세포주 손상에 대한 굴 효소 가수분해물의 보호 효과)

  • Park, Si-Hyang;Moon, Sung-Sil;Xie, Cheng-Liang;Choung, Se-Young;Choi, Yeung-Joon
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.43 no.8
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    • pp.1166-1173
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    • 2014
  • This study investigated the detoxification effects of enzymatic hydrolysate from oyster on acetaminophen-induced toxicity using HepG-2 cells. Oyster hydrolysate was made with 1% Protamex and 1% Neutrase after treatment with transglutaminase (TGPN) or without (PN). Two types of oyster hydrolysate were added to human-derived HepG-2 hepatocytes damaged by acetaminophen, after which the survival rate of HepG-2 cell was measured. In addition, glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) activities in the culture media were evaluated. The survival rates of HepG-2 cells were $136.2{\pm}1.4%$ at $100{\mu}g/mL$ of TGPN and $179.6{\pm}3.8%$ at $200{\mu}g/mL$ of TGPN. These cell survival rates were higher compared to that of the negative control group ($60.7{\pm}3.2%$) treated only with acetaminophen. GOT activity was $38.3{\pm}0.2$ Karmen/mL in the negative control group, whereas it was $19.9{\pm}0.5$ for TGPN ($200{\mu}g/mL$) and $22.0{\pm}2.4$ Karmen/mL for PN ($200{\mu}g/mL$). GOT and GTP activities were shown to be dependent on TGPN concentration, and significant reduction in activities could be conformed. The detoxification efficacy of TGPN was higher compared to that of PN. These results suggest that oyster hydrolysate has potential as a healthy food or pro-drug for liver protection.

Gene Expression of Detoxification Enzymes in Tenebrio molitor after Fungicide Captan Exposure (살진균제인 캡탄 처리 후 갈색거저리의 해독효소 유전자 발현)

  • Jang, Ho am;Baek, Hyoung-Seon;Kim, Bo Bae;Kojour, Maryam Ali Mohammadie;Patnaik, Bharat Bhusan;Jo, Yong Hun;Han, Yeon Soo
    • Korean journal of applied entomology
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    • v.61 no.1
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    • pp.155-163
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    • 2022
  • The application of fungicides is indispensable to global food security, and their use has increased in recent times. Fungicides, directly or indirectly, have impacted insects, leading to genetic and molecular-level changes. Various detoxification mechanisms allow insects to eliminate reactive oxygen species (ROS) toxicity induced by agrochemicals including fungicides. In the present study, we analyzed the mRNA expression levels of detoxifying enzymes in Tenebrio molitor larvae following exposure to non-lethal doses (0.2, 2, and 20 ㎍/µL) of a fungicide captan. Transcripts of peroxidases (POXs), catalases (CATs), superoxide dismutases (SODs), and glutathione-s-transferases (GSTs) were screened from the T. molitor transcriptome database. RT-qPCR analysis showed that TmPOX5 mRNA increased significantly 24 h post-captan exposure. A similar increase was noticed for TmSOD4 mRNA 3 h post-captan exposure. Moreover, the expression of TmCAT2 mRNA increased significantly 24 h post-treatment with 2 ㎍/µL captan. TmGST1 and TmGST3 mRNA expression also increased noticeably after captan exposure. Taken together, these results suggest that TmPOX5 and TmSOD4 mRNA can be used as biomarkers or xenobiotics sensors for captan exposure in T. molitor, while other detoxifying enzymes showed differential expression.