• Title/Summary/Keyword: genetic toxicity

Search Result 212, Processing Time 0.032 seconds

Isolation and mRNA Expression of Metallothionein Isoforms from Rockbream Oplegnathus fasciatus (돌돔(Oplegnathus fasciatus)으로부터 Metallothionein 유전자 Isoform들의 분리 및 발현 특징 분석)

  • Lee, Sang-Yoon;Nam, Yoon-Kwon
    • Korean Journal of Fisheries and Aquatic Sciences
    • /
    • v.44 no.2
    • /
    • pp.126-140
    • /
    • 2011
  • Genetic determinants of two metallothionein isoforms (MT-A and MT-B) were isolated and characterized from the perciform species, rockbream (Oplegnathus fasciatus). Rockbream MT-A and MT-B shared a high degree of homology at amino acid levels with representative orthologs from other perciform species, especially with respect to the conserved cysteine residues. At the genomic level, both MT-A and MT-B genes represent a tripartite structure typical of vertebrate MT genes. However, rockbream MT-B showed unusually large introns (1.2 kb and 0.8 kb for intron I and II, respectively), a phenomenon that has rarely been seen in other vertebrate MT genes. MT-A and MT-B transcripts were ubiquitously detected in a wide array of tissues, wherein brain and eye showed the highest basal expression levels, and the fin exhibited the lowest expression of both isoforms. The basal expression of MT-A in most tissues was significantly higher (ranging from 4- to 10-fold) than that of MT-B. Upon heavy metal exposures to Cd, Cu or Zn at 25 ppb for 48 h, MT-A and MT-B transcripts in the liver were significantly activated by Cd and moderately by Zn. On the other hand, exposure to Cu did not result in alterations of MT-A, nor in the significant suppression of MT-B. Following bacterial challenges with Escherichia coli, Edwardsiella tarda or Streptococcus iniae, MT isoforms in the liver, kidney and spleen were highly modulated and exhibited a pattern that was dependent on the bacterial species, tissues and isoforms. These results suggest that the two MT isoforms could be taken into account as potential indicators of metal toxicity and immune perturbations of this aquaculture-relevant species.

Stability in Immunomodulation Activity of Irradiated Angelica gigas Nakai (방사선 조사 당귀(Angelica gigas)의 면역활성 안정성)

  • 조성기;박혜란;유영법;송병철;이성태
    • Journal of the Korean Society of Food Science and Nutrition
    • /
    • v.29 no.1
    • /
    • pp.134-139
    • /
    • 2000
  • Angelica gigas Nakai (danggui) is a popular herb which has been used as a blood-building decoction for recovery from weakness in the Chinese medicine. Its demand increased in functional foods and pharmaceutical industries. For its hygiene, fumigation has been used, but the use of fumigants are going to be prohibited for food processing. In order to investigate gamma irradiation technique for hygiene of danggui, the immunomodulation activity of danggui after irradiation was examined. The water extract of irradiated danggui showed a strong mitogenic effect on splenocytes in vitro to the same level of lipopolysaccharide (LPS) and phytohemagglutinin (PHA). The effect was not different from that of non-danggui. It was tested whether there was any difference between irradiated and non-irradiated danggui in effects on the secretion of antibodies and graft versus host reaction in vivo. It turned out that intraperitoneal (i.p.) administration of the extract of irradiated danggui for 4 days remarkably increased the number of antibody-secreting cells in mice injected with sheep red blood cells (SRBC). Splenomegaly, due to graft versus host reacton, was also increased after 7 days i.p. administration of the extract of danggui in mice injected with allogeneic splenocytes. In these two in vivo test, the effect were not different from those of non-irradiated danggui. These results indicated that immunomodulation activity of danggui might be preserved after irradiation. In the other experiments (data not shown), the irradiated danggui was stable in active component analysis and safe in genetic toxicity test. In further research, the stability in other physiological activity of irradiated danggui will have to be proved before practical application of irradiation for hygiene.

  • PDF

A case of acute liver injury caused by folk remedy (민간요법으로 유발된 급성 간손상 환자 1례에 대한 소고)

  • Lee, Seong-Jong;An, Joung-Jo;Jo, Hyun-Kyung;Yoo, Ho-Rhyong;Seol, In-Chan;Kim, Yoon-Sik
    • Journal of Haehwa Medicine
    • /
    • v.18 no.1
    • /
    • pp.83-88
    • /
    • 2009
  • Recently, herbal drugs haver been used world wide. and generally regarded as safe with no serious adverse reaction. Drug-induced liver injury (DILI) is one of frequent cause of liver diseases. If DILI is not treated, it can be developed into liver cirrhosis, hepatoma, etc. Currently, DILI has been reported to be common cause of acute hepatitis, and oriental medicine and folk remedy are not exception. We encountered one case of DILI, cause by folk remedy. Patients complained chest discomfort, yellow skin and urine, nausea, vomiting. Lab test showed elevated level of aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transpeptidase (r-GTP), total bilirubin (TB). We estimated acute DILI and stopped taking folk medication made by himself. After 1 week of treatment, the clinical symptoms and liver function improved. Genetic and environmental factors as well as drug itself decide the hepatic toxicity, and the major DILI are belonged in acute type. So we need to get more attention to folk medication to help preventing the DILI cause by folk remedy.

  • PDF

Induction of Cytochrome P45O 1A and 2B by $\alpha$- and ${\beta}-lonone$ in Sprague Dawley Rats

  • Jeong, Tae-Cheon;Jeong, Hye-Gwang;Chun, Yong-Jin;Yun, Chul-Ho;Moon, Chang-Kiu;Lee, Hye-Sook;Han, Sang-Seop;Lee, Eung-Seok
    • Archives of Pharmacal Research
    • /
    • v.25 no.2
    • /
    • pp.197-201
    • /
    • 2002
  • ${\beta}-lonone$ has been reported to induce the cytochrome P45O (P45O) 2B1 in rats. In this study, the effects of ${\beta}-ionone$ and an isomer, ${\alpha}-ionone$, on liver P45O IA and 2B expression in Sprague Dawley rats were investigated . Subcutaneous administration of ${\alpha}-$ and ${\beta}-lonone$ 72 and 48hr prior to sacrificing the animals induced the liver microsomal P45O 1A and 2B proteins. P45O 2Bl induction was associated with the accumulation of its corresponding mRNA. 1 Induction by ${\beta}-lonone$ was much higher than that by ${\alpha}-ionone$-ionone in both the mRNA and protein levels. When the route of administration was compared, P45O 2B was induced more strongly after oral administration compared to that after subcutaneous injection. A single oral dose of 100, 300 and 600 mg/kg of ${\alpha}-$ and ${\beta}-lonone$ for 24 h induced P45O 2B1 -selective pentoxyresorufin Odepentylase activity comparably in a dose-dependent manner In addition, ${\alpha}-$ and ${\beta}-lonone$ induced the P45O 1A and 2B proteins. These results suggest that ${\alpha}-$ and ${\beta}-lonone$ might be potent P45O 2Bl inducers in rats, and that both ionones may be useful for examining the role of metabolic activation in chemical-induced toxicity where metabolic activation is required.

Agricultural Methods for Toxicity Alleviation in Metal Contaminated Soils: A Review

  • Arunakumara, Kkiu;Walpola, Buddhi Charana;Yoon, Min-Ho
    • Korean Journal of Soil Science and Fertilizer
    • /
    • v.46 no.2
    • /
    • pp.73-80
    • /
    • 2013
  • Due to the fact that possible risk associated with soil-crop-food chain transfer, metal contamination in croplands has become a major topic of wide concern. Accumulation of toxic metals in edible parts of crops grown in contaminated soils has been reported from number of crops including rice, soybean, wheat, maize, and vegetables. Therefore, in order to ensure food safety, measures are needed to be taken in mitigating metal pollution and subsequent uptake by crop plants. Present paper critically reviewed some of the cost effective remediation techniques used in minimizing metal uptake by crops grown in contaminated soils. Liming with different materials such as limestone ($CaCO_3$), burnt lime (CaO), slaked lime [$Ca(OH)_2$], dolomite [$CaMg(CO_3)_2$], and slag ($CaSiO_3$) has been widely used because they could elevate soil pH rendering metals less-bioavailable for plant uptake. Zn fertilization, use of organic amendments, crop rotation and water management are among the other techniques successfully employed in reducing metal uptake by crop plants. However, irrespectively the mitigating measure used, heterogeneous accumulation of metals in different crop species is often reported. The inconsistency might be attributed to the genetic makeup of the crops for selective uptake, their morphological characteristics, position of edible parts on the plants in respect of their distance from roots, crop management practices, the season and to the soil characteristics. However, a sound conclusion in this regard can only be made when more scientific evidence is available on case-specific researches, in particular from long-term field trials which included risks and benefits analysis also for various remediation practices.

C9orf72-Associated Arginine-Rich Dipeptide Repeat Proteins Reduce the Number of Golgi Outposts and Dendritic Branches in Drosophila Neurons

  • Park, Jeong Hyang;Chung, Chang Geon;Seo, Jinsoo;Lee, Byung-Hoon;Lee, Young-Sam;Kweon, Jung Hyun;Lee, Sung Bae
    • Molecules and Cells
    • /
    • v.43 no.9
    • /
    • pp.821-830
    • /
    • 2020
  • Altered dendritic morphology is frequently observed in various neurological disorders including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), but the cellular and molecular basis underlying these pathogenic dendritic abnormalities remains largely unclear. In this study, we investigated dendritic morphological defects caused by dipeptide repeat protein (DPR) toxicity associated with G4C2 expansion mutation of C9orf72 (the leading genetic cause of ALS and FTD) in Drosophila neurons and characterized the underlying pathogenic mechanisms. Among the five DPRs produced by repeat-associated non-ATG translation of G4C2 repeats, we found that arginine-rich DPRs (PR and GR) led to the most significant reduction in dendritic branches and plasma membrane (PM) supply in Class IV dendritic arborization (C4 da) neurons. Furthermore, expression of PR and GR reduced the number of Golgi outposts (GOPs) in dendrites. In Drosophila brains, expression of PR, but not GR, led to a significant reduction in the mRNA level of CrebA, a transcription factor regulating the formation of GOPs. Overexpressing CrebA in PR-expressing C4 da neurons mitigated PM supply defects and restored the number of GOPs, but the number of dendritic branches remained unchanged, suggesting that other molecules besides CrebA may be involved in dendritic branching. Taken together, our results provide valuable insight into the understanding of dendritic pathology associated with C9-ALS/FTD.

Purification and Physicochemical Properties of Superoxide Anion Radical Scavenger from Capsella bursa-pastoris (냉이(Capsella bursa-pastoris)로부터 Superoxide Anion Radical 소거물질의 정제 및 이화학적 성질)

  • Kwak, Jae-Hyock;Kweon, Mee-Hyang;Ra, Kyung-Soo;Sung, Ha-Chin;Yang, Han-Chul
    • Korean Journal of Food Science and Technology
    • /
    • v.28 no.1
    • /
    • pp.184-189
    • /
    • 1996
  • A scavenger of superoxide anion radical which causes oxygen toxicity was isolated from Capsella bursa-pastoris, and its physicochemical properties were investigated. The scavenger was isolated and purified by solvent fractionation and liquid column chromatographies (Amberlite XAD-2, Sephadex LH-20, Bio gel P-2, ODS (silica gel with 100% octadecyl silanization)). An active compound of 0.25 g was finally isolated by Fast Protein Liquid chromatography (FPLC) from 100 g ethanol extract of Capsella bursa-pastoris. A 50% decrease of superoxide anion radical was obtained with the scavenger compound of 0.58 g. The compound was assumed to be a phenolic glycoside from its physicochemical properties.

  • PDF

Effect of SLCO1B1 T521C on Statin-induced Myotoxicity: A Systematic Review and Meta-analysis (SLCO1B1 T521C가 스타틴에 의한 근육독성 발생에 미치는 영향: 체계적 문헌고찰 및 메타분석)

  • Lee, Young Sook;Chun, Pusoon
    • Korean Journal of Clinical Pharmacy
    • /
    • v.28 no.4
    • /
    • pp.320-332
    • /
    • 2018
  • Background: This study was performed to clarify the effect of SLCO1B1 T521C on statin-induced myotoxicity. Methods: The PubMed, Embase, Ovid, and Cochrane Library databases were searched for all published studies between database inception and April 2018. Using Review Manager 5, the pooled odds ratio (OR) and corresponding 95% confidence interval (CI) were determined to assess the effect of SLCO1B1 T521C on statin-induced myotoxicity by using different genetic models. Results: Eleven observational studies and one randomized controlled trial were included in the meta-analysis. The pooled analysis showed that the incidence of statin-induced myotoxicity was significantly associated with the SLCO1B1 521C variant allele. Among patients using statins, the incidence of myotoxicity was higher in those carrying the 521TC or 521CC variant than in those carrying the 521TT variant in the dominant model (TC + CC vs TT, OR: 1.57; 95% CI: 1.20, 2.05; p = 0.001). The 521TC genotype was associated with a higher risk of myotoxicity than the 521TT genotype (OR: 1.42; 95% CI: 1.09, 1.86; p = 0.009). Furthermore, the incidence of myotoxicity was higher in 521CC carriers than in 521TC carriers (OR: 1.40; 95% CI: 1.06, 1.83; p = 0.02) and noticeably higher in 521CC carriers than in 521TT carriers (OR: 2.26; 95% CI: 1.23, 4.17; p = 0.009). Conclusion: The identification of individuals with the SLCO1B1 521C variant allele prior to the initiation of statin therapy might be useful to predict the risk of toxicity development, determine the individual dose, and prevent myotoxicity.

Computer-aided drug design of Azadirachta indica compounds against nervous necrosis virus by targeting grouper heat shock cognate protein 70 (GHSC70): quantum mechanics calculations and molecular dynamic simulation approaches

  • Islam, Sk Injamamul;Saloa, Saloa;Mahfuj, Sarower;Islam, Md Jakiul;Jahan Mou, Moslema
    • Genomics & Informatics
    • /
    • v.20 no.3
    • /
    • pp.33.1-33.17
    • /
    • 2022
  • Nervous necrosis virus (NNV) is a deadly infectious disease that affects several fish species. It has been found that the NNV utilizes grouper heat shock cognate protein 70 (GHSC70) to enter the host cell. Thus, blocking the virus entry by targeting the responsible protein can protect the fishes from disease. The main objective of the study was to evaluate the inhibitory potentiality of 70 compounds of Azadirachta indica (Neem plant) which has been reported to show potential antiviral activity against various pathogens, but activity against the NNV has not yet been reported. The binding affinity of 70 compounds was calculated against the GHSC70 with the docking and molecular dynamics (MD) simulation approaches. Both the docking and MD methods predict 4 (PubChem CID: 14492795, 10134, 5280863, and 11119228) inhibitory compounds that bind strongly with the GHSC70 protein with a binding affinity of -9.7, -9.5, -9.1, and -9.0 kcal/mol, respectively. Also, the ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties of the compounds confirmed the drug-likeness properties. As a result of the investigation, it may be inferred that Neem plant compounds may act as significant inhibitors of viral entry into the host cell. More in-vitro testing is needed to establish their effectiveness.

CBP-Mediated Acetylation of Importin α Mediates Calcium-Dependent Nucleocytoplasmic Transport of Selective Proteins in Drosophila Neurons

  • Cho, Jae Ho;Jo, Min Gu;Kim, Eun Seon;Lee, Na Yoon;Kim, Soon Ha;Chung, Chang Geon;Park, Jeong Hyang;Lee, Sung Bae
    • Molecules and Cells
    • /
    • v.45 no.11
    • /
    • pp.855-867
    • /
    • 2022
  • For proper function of proteins, their subcellular localization needs to be monitored and regulated in response to the changes in cellular demands. In this regard, dysregulation in the nucleocytoplasmic transport (NCT) of proteins is closely associated with the pathogenesis of various neurodegenerative diseases. However, it remains unclear whether there exists an intrinsic regulatory pathway(s) that controls NCT of proteins either in a commonly shared manner or in a target-selectively different manner. To dissect between these possibilities, in the current study, we investigated the molecular mechanism regulating NCT of truncated ataxin-3 (ATXN3) proteins of which genetic mutation leads to a type of polyglutamine (polyQ) diseases, in comparison with that of TDP-43. In Drosophila dendritic arborization (da) neurons, we observed dynamic changes in the subcellular localization of truncated ATXN3 proteins between the nucleus and the cytosol during development. Moreover, ectopic neuronal toxicity was induced by truncated ATXN3 proteins upon their nuclear accumulation. Consistent with a previous study showing intracellular calcium-dependent NCT of TDP-43, NCT of ATXN3 was also regulated by intracellular calcium level and involves Importin α3 (Imp α3). Interestingly, NCT of ATXN3, but not TDP-43, was primarily mediated by CBP. We further showed that acetyltransferase activity of CBP is important for NCT of ATXN3, which may acetylate Imp α3 to regulate NCT of ATXN3. These findings demonstrate that CBP-dependent acetylation of Imp α3 is crucial for intracellular calcium-dependent NCT of ATXN3 proteins, different from that of TDP-43, in Drosophila neurons.