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      Analysis of the Toxicity and Histopathology Induced by the Oral Administration of Pseudanabaena galeata and Geitlerinema splendidum (Cyanobacteria) Extracts to Mice

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          Abstract

          Cyanobacteria are common members of the freshwater microbiota in lakes and drinking water reservoirs, and are responsible for several cases of human intoxications in Brazil. Pseudanabaena galeata and Geitlerinema splendidum are examples of the toxic species that are very frequently found in reservoirs in Sao Paulo, which is the most densely populated area in Brazil. In the search for toxic strains collected from water reservoirs and maintained in the Cyanobacterial Culture Collection (CCIBt) of the Institute of Botany of Brazil, the acetic acid extracts (AE) of P. galeata CCIBt 3082 and G. splendidum CCIBt 3223 were analyzed by planar chromatography, which indicated the absence of cyanotoxins. Animal tests were then carried out, and both extracts were found to induce toxic effects in mice when administered intraperitoneally. The present study aimed to investigate whether the oral ingestion of the above mentioned cyanobacteria extracts would also induce toxic effects in mice. Necropsy and histopathological studies were conducted using tissue samples from the animals, which were euthanized one week after the administration of the extracts. The AE of P. galeata did not cause death but did induce transient symptoms, including eyebrow ptosis, straub tail, and pain. The euthanized animals presented hemorrhage in the liver, whereas the histological analysis showed disorganization of the hepatic parenchyma, necrosis, hyperemia, and proximity of the centrilobular vein in the liver. In addition, alterations in the convoluted tubules of the kidneys were observed, and the lungs were unaffected. The AE of G. splendidum caused only one death, and induced transient symptoms, such as dyspnea, paralysis, and pain, in the other mice. The necropsy of the euthanized mice showed hemorrhage in the lungs and liver. The lungs presented hemorrhagic focuses, alveolar collapse, and granulomatous foci. The liver presented hemorrhagic and enlarged sinusoids, hyperemia, proximity of the centrilobular vein, and disorganization of the hepatic parenchyma. Some areas also exhibited an inflammatory infiltrate and calcified tissue inside blood vessels. Necrosis and rupture of the convoluted tubule cells were observed in the kidneys. Further analysis of the both extracts indicated the lack of hemolytic activity, and the presence of two unknown anti-AChE substances in the AE of G. splendidum. Thus, P. galeata and G. splendidum are producers of novel toxins that affect mammals when administered orally.

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          Cyanobacterial microcystin-LR is a potent and specific inhibitor of protein phosphatases 1 and 2A from both mammals and higher plants.

          The cyclic heptapeptide, microcystin-LR, inhibits protein phosphatases 1 (PP1) and 2A (PP2A) with Ki values below 0.1 nM. Protein phosphatase 2B is inhibited 1000-fold less potently, while six other phosphatases and eight protein kinases tested are unaffected. These results are strikingly similar to those obtained with the tumour promoter okadaic acid. We establish that okadaic acid prevents the binding of microcystin-LR to PP2A, and that protein inhibitors 1 and 2 prevent the binding of microcystin-LR to PP1. We discuss the possibility that inhibition of PP1 and PP2A accounts for the extreme toxicity of microcystin-LR, and indicate its potential value in the detection and analysis of protein kinases and phosphatases.
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            Marine natural products.

            This review covers the literature published in 2011 for marine natural products, with 870 citations (558 for the period January to December 2011) referring to compounds isolated from marine microorganisms and phytoplankton, green, brown and red algae, sponges, cnidarians, bryozoans, molluscs, tunicates, echinoderms, mangroves and other intertidal plants and microorganisms. The emphasis is on new compounds (1152 for 2011), together with the relevant biological activities, source organisms and country of origin. Biosynthetic studies, first syntheses, and syntheses that lead to the revision of structures or stereochemistries, have been included.
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              Marine natural products.

              This review covers the literature published in 2007 for marine natural products, with 948 citations(627 for the period January to December 2007) referring to compounds isolated from marine microorganisms and phytoplankton, green algae, brown algae, red algae, sponges, cnidarians,bryozoans, molluscs, tunicates, echinoderms and true mangrove plants. The emphasis is on new compounds (961 for 2007), together with the relevant biological activities, source organisms and country of origin. Biosynthetic studies, first syntheses, and syntheses that lead to the revision of structures or stereochemistries, have been included.1 Introduction, 2 Reviews, 3 Marine microorganisms and phytoplankton, 4 Green algae, 5 Brown algae, 6 Red algae, 7 Sponges, 8 Cnidarians, 9 Bryozoans, 10 Molluscs, 11 Tunicates (ascidians),12 Echinoderms, 13 Miscellaneous, 14 Conclusion, 15 References.
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                Author and article information

                Journal
                Mar Drugs
                Mar Drugs
                marinedrugs
                Marine Drugs
                MDPI
                1660-3397
                22 January 2014
                January 2014
                : 12
                : 1
                : 508-524
                Affiliations
                [1 ]Immunopathology Laboratory, Butantan Institute, Av. Vital Brasil, 1500, Sao Paulo SP 05503-900, Brazil; E-Mail: joycecarolmartins@ 123456ig.com.br
                [2 ]Phycology Section, Institute of Botany, Av. Miguel Stéfano, 3687, Sao Paulo SP 04301-902, Brazil; E-Mails: angelsgarcia@ 123456uol.com.br (A.N.G.); geanne.conserva@ 123456yahoo.com.br (G.A.A.C.); celialsant@ 123456yahoo.com.br (C.L.S.); lretz@ 123456uol.com.br (L.R.C.)
                [3 ]Department of Genetics, Butantan Institute, Av. Vital Brasil, 1500, Sao Paulo SP 05503-900, Brazil; E-Mail: adriana.neves@ 123456butantan.gov.br
                Author notes
                [* ] Author to whom correspondence should be addressed; E-Mail: marisarangel2112@ 123456gmail.com or marisa.rangel@ 123456butantan.gov.br ; Tel./Fax: +55-11-26279777.
                Article
                marinedrugs-12-00508
                10.3390/md12010508
                3917284
                24451192
                fd1067b9-1c59-4dec-8499-73094372b208
                © 2014 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                : 01 November 2013
                : 30 December 2013
                : 30 December 2013
                Categories
                Article

                Pharmacology & Pharmaceutical medicine
                cyanobacteria,cyanotoxins,water reservoirs,histopathology,mouse toxicity

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