Pub Date : 2003-05-01DOI: 10.1080/08865140390427418
M. Vore
The identification of the family of multidrug-resistance-associated proteins (MRPs) has provided new understanding regarding mechanisms of absorption, distribution, elimination, and toxicity of both endoand xenobiotics. Just over 10 years ago, Cole et al. (1) identified MRP1, the founding member of this family, in a multidrug-resistant human lung cancer cell line that did not express MDR1 P-glycoprotein. This issue of Comments on Toxicology is devoted to three topics related to MRP2, the second member of this family to be identified, and the role it plays in both mediating and protecting against toxicity. MRP2 (ABCC2) is the transporter that mediates the biliary excretion of numerous drugs and their metabolites. The first article by Christoph Dietrich and colleagues, details several examples in which MRP2 protects the organism from toxicity by preventing the absorption of dietary carcinogens and, conversely, promotes toxicity of chemicals, such as a-naphthylisothiocyanate, by eliminating them from the hepatocyte but concentrating them in bile, where they then induce local damage to cholangiocytes, the cells lining the biliary tree. The article by Ned Ballatori and colleagues summarizes the evidence demonstrating that MRP2 mediates the secretion of glutathione (GSH) into bile, which contributes significantly to the generation of bile flow. MRP2-mediated transport of GSH, either alone or as a part of a complex, is a two-edged sword, resulting in protection of cholangiocytes and enterocytes downstream from the hepatocyte, but also in depletion of the hepatocyte of GSH under certain conditions, such as in the presence of arsenite. MRP2-mediated efflux of GSH
多药耐药相关蛋白(MRPs)家族的鉴定为内源性和外源性抗生素的吸收、分布、消除和毒性机制提供了新的认识。就在10多年前，Cole等人(1)在一种不表达MDR1 p -糖蛋白的多药耐药人肺癌细胞系中发现了该家族的创始成员MRP1。本期《毒理学评论》专门讨论与MRP2相关的三个主题，MRP2是该家族的第二个成员，它在介导和保护毒性方面发挥的作用。MRP2 (ABCC2)是介导多种药物及其代谢物胆汁排泄的转运蛋白。Christoph Dietrich及其同事的第一篇文章详细介绍了几个例子，其中MRP2通过阻止饮食致癌物的吸收来保护生物体免受毒性，相反，通过将化学物质(如a-naphthylisothiocyanate)从肝细胞中清除，但将其集中在胆汁中，从而促进化学物质(如a-naphthylisothiocyanate)的毒性，然后在胆汁中诱导胆管细胞(胆树的细胞)局部损伤。Ned Ballatori及其同事的文章总结了MRP2介导谷胱甘肽(GSH)分泌到胆汁中的证据，这对胆汁流动的产生有重要作用。mrp2介导的GSH运输，无论是单独的还是作为复合物的一部分，都是一把双刃剑，导致肝细胞下游的胆管细胞和肠细胞受到保护，但在某些条件下，如在亚砷酸盐存在的情况下，也会导致肝细胞的GSH消耗。mrp2介导的谷胱甘肽外排
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Some cyanobacteria produce microcystins, hepatotoxins with strong cytotoxicity mediated by inhibition of protein phosphatases. New evidence, however, suggests other toxic mechanisms, including oxidative damage and disruption of osmoregulation. Augmented levels of reactive oxygen species, lipid peroxides, and DNA damage were reported after microcystin exposure. The tripeptide glutathione (GSH) is one of the most important antioxidants, and it was reported that microcystin is conjugated with GSH. Microcystin conjugation could deplete the intracellular stores of GSH, leaving the cell more susceptible to oxidative stress. Inhibition of Na + , K + -ATPase by microcystin may be responsible for osmoregulation failure in freshwater fishes.
一些蓝藻产生微囊藻毒素，一种通过抑制蛋白磷酸酶介导的具有强细胞毒性的肝毒素。然而，新的证据表明了其他的毒性机制，包括氧化损伤和渗透调节的破坏。据报道，暴露于微囊藻毒素后，活性氧、脂质过氧化物和DNA损伤水平增加。三肽谷胱甘肽(GSH)是最重要的抗氧化剂之一，微囊藻毒素与谷胱甘肽偶联。微囊藻毒素结合可以消耗细胞内储存的谷胱甘肽，使细胞更容易受到氧化应激。微囊藻毒素对Na +， K + - atp酶的抑制可能是淡水鱼渗透调节失败的原因。
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The Guest Editor for this issue of Comments on Toxicology is Dr. José M. Monserrat, Professor of Biochemistry in the Department of Physiological Sciences at the Federal University of Rio Grande, Rio Grande, Brazil. Dr. Monserrat is a marine biologist with interest in toxins, especially saltwater phycotoxins. He has a particular interest in the cyanobacteria and the various toxins produced by this organism. Dr. Monserrat has been an active researcher in this field for a number of years and has carried out numerous monitoring programs in Brazil. The following overview of this issue was prepared by Dr. Monserrat.
本期《毒理学评论》的客座编辑是巴西里奥格兰德联邦大学生理科学系生物化学教授jos M. Monserrat博士。蒙塞拉特博士是一位海洋生物学家，对毒素，特别是盐水藻毒素感兴趣。他对蓝藻和这种有机体产生的各种毒素特别感兴趣。Monserrat博士多年来一直是该领域的活跃研究人员，并在巴西开展了许多监测项目。下面这个问题的概述是蒙塞拉特博士编写的。
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C. Alvarez, M. Tejuca, I. Pazos, M. E. Lanio, A. Garateix, A. Aneiros
Toxin research in Cuba has made some important contributions to the field in recent decades. Most of the work carried out on marine toxins has been devoted to the isolation, purification, and characterization of polypeptide substances. The purification, molecular, and functional characterization as well as the pharmacological properties of these toxins are revised. The toxin battery described includes new biomolecules: sticholysins I and II, cytolysins from Stichodactyla helianthus; BgK and ShK, two K + channel blockers purified from Bunodosoma granulifera and S. helianthus, respectively; and BgII and III, two Na + channeltoxinsfrom B. granulifera.
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J. Yunes, N. T. Cunha, L. P. Barros, L. Proença, José María Monserrat
Blooms of Cylindrospermopsis raciborskii and Anabaena spiroides were studied in relation to their toxins composition, geographical locations, and other characteristics of the waters in the southern region of Brazil. All forms of Cylindrospermopsis were paralytic shellfish toxin producers, with a similar profile of the toxins. Anabaena blooms were studied in relation to the production of anatoxin-a(S). In all samples containing Anabaena spiroides, a positive result was found when the AChE inhibition technique was used. Methods applied for both studies are very convenient for monitoring this large region and give a reasonable view of the present situation of water reservoirs in southern Brazil.
{"title":"Cyanobacterial Neurotoxins from Southern Brazilian Freshwaters","authors":"J. Yunes, N. T. Cunha, L. P. Barros, L. Proença, José María Monserrat","doi":"10.1080/08865140302426","DOIUrl":"https://doi.org/10.1080/08865140302426","url":null,"abstract":"Blooms of Cylindrospermopsis raciborskii and Anabaena spiroides were studied in relation to their toxins composition, geographical locations, and other characteristics of the waters in the southern region of Brazil. All forms of Cylindrospermopsis were paralytic shellfish toxin producers, with a similar profile of the toxins. Anabaena blooms were studied in relation to the production of anatoxin-a(S). In all samples containing Anabaena spiroides, a positive result was found when the AChE inhibition technique was used. Methods applied for both studies are very convenient for monitoring this large region and give a reasonable view of the present situation of water reservoirs in southern Brazil.","PeriodicalId":402874,"journal":{"name":"Comments on Toxicology","volume":"10 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2003-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114555242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This is a review of the regional (South America) harmful algae blooms associated with paralytic shellfish poisoning (PSP) phycotoxin producers. This review provides a survey of the most relevant recorded events known to have been caused by microalgae that are PSP producers in this region. The geographical distribution of harmful species of PSP phycotoxins producers in sea and inland fresh water are shown. The variation of molluscs toxicity measured by the mouse bioassay, high performance liquid chromatography with fluorescence detection, and analysis by liquid chromatography and mass spectroscopy of these PSP phycotoxins in Argentina, Brazil, Chile, Uruguay, and Venezuela is summarized. I hope this review provides reference material suitable for researchers, students, managers, health professionals, and political authorities. Another goal is to stimulate research in this area to answer critical questions to improve our understanding of PSP-producing harmful algal bloom species and the significant effects that they have upon aquatic systems and our lives in this part of the world.
{"title":"Paralytic shellfish poisoning phycotoxins: Occurrence in South America","authors":"N. Lagos","doi":"10.1080/08865140302429","DOIUrl":"https://doi.org/10.1080/08865140302429","url":null,"abstract":"This is a review of the regional (South America) harmful algae blooms associated with paralytic shellfish poisoning (PSP) phycotoxin producers. This review provides a survey of the most relevant recorded events known to have been caused by microalgae that are PSP producers in this region. The geographical distribution of harmful species of PSP phycotoxins producers in sea and inland fresh water are shown. The variation of molluscs toxicity measured by the mouse bioassay, high performance liquid chromatography with fluorescence detection, and analysis by liquid chromatography and mass spectroscopy of these PSP phycotoxins in Argentina, Brazil, Chile, Uruguay, and Venezuela is summarized. I hope this review provides reference material suitable for researchers, students, managers, health professionals, and political authorities. Another goal is to stimulate research in this area to answer critical questions to improve our understanding of PSP-producing harmful algal bloom species and the significant effects that they have upon aquatic systems and our lives in this part of the world.","PeriodicalId":402874,"journal":{"name":"Comments on Toxicology","volume":"3 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2003-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122225000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This special issue is devoted to the analysis of the effects of toxins produced by different kinds of organisms. Toxinology is the science that studies the chemical properties and biological effects of toxic substances produced or accumulated in living organisms. Probably, if one term were used to define toxinology, the word would be ‘‘diversity’’ Diversity of organisms that produce tremendously diverse chemical compounds that in turn possess diverse biological targets, such as ion channels or enzymes (acetylcholinesterase or phosphatases). An important point of this issue is that all the contributors are researchers born in Latin American countries. This fact reflects the importance and efforts that are devoted to this topic in this region. As one of the contributors stated, the extended coastal regions and coral reefs of Latin American countries are rich with biological diversity of toxin-producing organisms, like Cnidarians for example. As a consequence of the chemical diversity, the approaches that the different authors employed in their reviews are diverse. Some articles are of a biochemical and pharmacological nature, others focus on the detection and quantification of toxins in aquatic environments from a more ecotoxicological point of view. Finally, toxinology as a science opens the door for the potential therapeutics use of natural compounds, a fact well stated in several of the reviews in this issue. In the last several years, the study of marine-natural products has gained attention through improved biological screening methods (1). In several Latin American countries, zootherapy and phytotherapy, using chemicals derived directly or indirectly from animals and vegetable sources has become common practice (2). We expect in the near future that a convergence of ideas from toxinology and ethnopharmacology will develop. This last point also stresses that the discovery of molecules beneficial for human health is closely related to the preservation of the natural
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Marine organisms have provided an interesting array of biologically active peptides and proteins. Many of these compounds have proven to be excellent tools for probing biological functions as they are highly site-specific in their actions. In this review, we have highlighted recent work regarding Cnidarian toxins from hydrozoans, scyphozoans, cubozoans, and anthozoans. Structure-activity studies of anthozoan toxins indicate potential therapeutical applications.
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José Carlos de Freitas, Marisa Rangel, Joacir Stolarz Oliveira, A. J. Zaharenko, E. Rozas
Over the last 20 years, our group has collected different species of marine organisms occurring in the Brazilian coastline. The pharmacological approach is the evaluation of effects of organic extracts, or purified and isolated compounds in laboratory animals, organs, tissues, and cells to define the profile of biological activity and the mechanisms of action. Different bioassays are currently used including hemolytic cytotoxicity, neurotoxicity, and neuromuscular junction preparations. Furthermore, biologically active substances are being isolated from dinoflagellates, sponges, sea anemones, and puffer fish collected in the Sa ¨ o Sebastia ¨ o Channel (Sa ¨ o Paulo State, Brazil) and from the mollusk Conus regius collected in the Fernando de Noronha Archipelago, Pernambuco State, Brazil. These results suggest it may be very worthwhile to extend our studies for new bioactive compounds along the Brazilian coastline.
在过去的20年里，我们的团队收集了巴西海岸线上不同种类的海洋生物。药理学方法是评价有机提取物或纯化和分离的化合物在实验动物、器官、组织和细胞中的作用，以确定生物活性的概况和作用机制。目前使用的不同生物测定方法包括溶血细胞毒性、神经毒性和神经肌肉接点制剂。此外，正在从Sa¨o Sebastia¨o海峡(巴西Sa¨Paulo州)收集的鞭毛类、海绵、海莲花和河豚鱼以及在巴西Pernambuco州Fernando de Noronha群岛收集的软体动物Conus regius中分离出生物活性物质。这些结果表明，沿着巴西海岸线扩展新的生物活性化合物的研究可能是非常值得的。
{"title":"An Outline of Marine Toxinology Studies in the Brazilian coast","authors":"José Carlos de Freitas, Marisa Rangel, Joacir Stolarz Oliveira, A. J. Zaharenko, E. Rozas","doi":"10.1080/08865140302425","DOIUrl":"https://doi.org/10.1080/08865140302425","url":null,"abstract":"Over the last 20 years, our group has collected different species of marine organisms occurring in the Brazilian coastline. The pharmacological approach is the evaluation of effects of organic extracts, or purified and isolated compounds in laboratory animals, organs, tissues, and cells to define the profile of biological activity and the mechanisms of action. Different bioassays are currently used including hemolytic cytotoxicity, neurotoxicity, and neuromuscular junction preparations. Furthermore, biologically active substances are being isolated from dinoflagellates, sponges, sea anemones, and puffer fish collected in the Sa ¨ o Sebastia ¨ o Channel (Sa ¨ o Paulo State, Brazil) and from the mollusk Conus regius collected in the Fernando de Noronha Archipelago, Pernambuco State, Brazil. These results suggest it may be very worthwhile to extend our studies for new bioactive compounds along the Brazilian coastline.","PeriodicalId":402874,"journal":{"name":"Comments on Toxicology","volume":"22 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2003-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128236540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A large number of metals in the environment enter the human body and exert diverse toxic effects on the immune system-forming cells. These effects may lead to the death of the cells through the mechanism responsible for apoptosis or necrosis, as well as for activation or suppression of immune functions. Activation or suppression of lymphocytes and antigen-presenting cells depends on the kind and concentration of metals in target cells. The metal-generated changes in protein activity, which induce signaling pathways, as well as changes in expression of genes able to regulate the production of such protein molecules as cytokines and their receptors and surface adhesion molecules, predominate in the immunotoxic effects. Insufficient activation or inhibited production of these proteins is manifested by a decreased immunity of the organism (immuno-suppression), whereas their overactivation induces hypersensitivity (allergy, autoimmunization). A growing amount of data confirm that the activation of proteins involved in cellular signaling and the activation of expression of genes regulating the synthesis of proteins participating in the immune response are associated with oxidative metabolism of immune cells. These data also provide evidence that the modulation effect of metals on the immune response proceeds through influencing the mechanisms that control the production of reactive oxygen species.
{"title":"Metal-Induced Modulation of Redox Cell-Signaling in the Immune System","authors":"W. Lutz, W. Wąsowicz","doi":"10.1080/08865140302422","DOIUrl":"https://doi.org/10.1080/08865140302422","url":null,"abstract":"A large number of metals in the environment enter the human body and exert diverse toxic effects on the immune system-forming cells. These effects may lead to the death of the cells through the mechanism responsible for apoptosis or necrosis, as well as for activation or suppression of immune functions. Activation or suppression of lymphocytes and antigen-presenting cells depends on the kind and concentration of metals in target cells. The metal-generated changes in protein activity, which induce signaling pathways, as well as changes in expression of genes able to regulate the production of such protein molecules as cytokines and their receptors and surface adhesion molecules, predominate in the immunotoxic effects. Insufficient activation or inhibited production of these proteins is manifested by a decreased immunity of the organism (immuno-suppression), whereas their overactivation induces hypersensitivity (allergy, autoimmunization). A growing amount of data confirm that the activation of proteins involved in cellular signaling and the activation of expression of genes regulating the synthesis of proteins participating in the immune response are associated with oxidative metabolism of immune cells. These data also provide evidence that the modulation effect of metals on the immune response proceeds through influencing the mechanisms that control the production of reactive oxygen species.","PeriodicalId":402874,"journal":{"name":"Comments on Toxicology","volume":"93 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122848151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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