title: Protective Effect of the Sulfated Agaran Isolated from the Red Seaweed Laurencia aldingensis Against Toxic Effects of the Venom of the Snake, Lachesis muta.
abstract: Snakebite is a serious occupational hazard affecting mainly rural populations of tropical and subtropical developing countries. Lachesis muta (Bushmaster) bites are extremely serious but are rarely reported in the literature. Bushmaster envenomings are characterized by intense local pain, edema, neurotoxicity, hypotension, local hemorrhage, and dramatic systemic alterations. Antivenom treatment has regularly been used for more than a century; however, it fails to neutralize local tissue damage and hemorrhage, leading to morbidity or disabilities in victims. Thus, the production and clinical use of antivenom must be improved. The present work characterizes, for the first time, a sulfated polysaccharide from the red seaweed, Laurencia aldingensis, including its neutralizing effect on some toxic activities of L. muta venom. Chemical and spectroscopic analyses showed that L. aldingensis produces sulfated agarans with the A-units partially C-2 sulfated or 6-O-methoxylated presetting the B-units in the cyclized (3,6-anhydro-α-L-galactose) or in the non-cyclized form (α-L-galactose). The latter is significantly substituted by sulfate groups on C-6. In vitro and in vivo assays showed that this sulfated agaran inhibited hemolysis, coagulation, proteolysis, edema, and hemorrhage of L. muta venom. Neutralization of hemorrhagic activity was also observed when the agaran was administered by different routes and after or before the venom injection. Furthermore, the agaran blocked the edema caused by a phospholipase A2isolated from the L. muta venom. Experimental evidence therefore indicates that the sulfated agaran of L. aldingensis has potential to aid antivenom therapy of accidents caused by L. muta venom and may help to develop more effective antivenom treatments of snake bites in general.
authors.affiliation: Department of Molecular and Cellular Biology, Federal Fluminense University, Niterói, Rio de Janeiro, CEP 24020-141, Brazil.
authors.forename: Ana Cláudia Rodrigues
authors.initials: AC
authors.lastname: da Silva
authors.affiliation: Department of Biochemistry and Molecular Biology, Federal University of Paraná, Curitiba, Paraná, CEP 81531-980, Brazil.
authors.forename: Luciana Garcia
authors.initials: LG
authors.lastname: Ferreira
authors.affiliation: Department of Biochemistry and Molecular Biology, Federal University of Paraná, Curitiba, Paraná, CEP 81531-980, Brazil. eugenia.duarte@pq.cnpq.br.
authors.forename: Maria Eugênia Rabello
authors.initials: ME
authors.lastname: Duarte
authors.affiliation: Secretary of São Paulo State for Environment, Institute of Botany, São Paulo, SP, CEP 04301-012, Brazil.
authors.forename: Mutue Toyota
authors.initials: MT
authors.lastname: Fujii
authors.affiliation: Laboratory of Biochemistry of Proteins from Animal Venoms, Research and Development Center, Ezequiel Dias Foundation, Belo Horizonte, Minas Gerais, CEP 30510-010, Brazil.
authors.forename: Eladio Flores
authors.initials: EF
authors.lastname: Sanchez
authors.affiliation: Department of Biochemistry and Molecular Biology, Federal University of Paraná, Curitiba, Paraná, CEP 81531-980, Brazil.
authors.forename: Miguel Daniel
authors.initials: MD
authors.lastname: Noseda
authors.affiliation: Department of Molecular and Cellular Biology, Federal Fluminense University, Niterói, Rio de Janeiro, CEP 24020-141, Brazil. andrefuly@id.uff.br.
authors.forename: André Lopes
authors.initials: AL
authors.lastname: Fuly
mesh_terms: D000818:Animals; D000997:Antivenins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control*; D006461:Hemolysis / Q000187:drug effects; D006470:Hemorrhage / Q000139:chemically induced / Q000517:prevention & control; D006801:Humans; D044722:Laurencia / Q000737:chemistry*; D051379:Mice; D054467:Phospholipases A2 / Q000008:administration & dosage; D010936:Plant Extracts / Q000737:chemistry; D011134:Polysaccharides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D059748:Proteolysis / Q000187:drug effects; D012624:Seaweed; D012909:Snake Bites / Q000188:drug therapy* / Q000503:physiopathology; D013431:Sulfates; D014757:Viper Venoms / Q000037:antagonists & inhibitors* / Q000633:toxicity; D017819:Viperidae
chemical_list: D000997:Antivenins; D010936:Plant Extracts; D011134:Polysaccharides; D013431:Sulfates; D014757:Viper Venoms; D054467:Phospholipases A2
keywords: Antivenom treatment; Chemical structure; Lachesis muta; Laurencia aldingensis; Snake venom; Sulfated agaran