title: Neutralization of Apis mellifera bee venom activities by suramin.
abstract: In this work we evaluated the ability of suramin, a polysulfonated naphthylurea derivative, to antagonize the cytotoxic and enzymatic effects of the crude venom of Apis mellifera. Suramin was efficient to decrease the lethality in a dose-dependent way. The hemoconcentration caused by lethal dose injection of bee venom was abolished by suramin (30 μg/g). The edematogenic activity of the venom (0.3 μg/g) was antagonized by suramin (10 μg/g) in all treatment protocols. The changes in the vascular permeability caused by A. mellifera (1 μg/g) venom were inhibited by suramin (30 μg/g) in the pre- and posttreatment as well as when the venom was preincubated with suramin. In addition, suramin also inhibited cultured endothelial cell lesion, as well as in vitro myotoxicity, evaluated in mouse extensor digitorum longus muscle, which was inhibited by suramin (10 and 25 μM), decreasing the rate of CK release, showing that suramin protected the sarcolemma against damage induced by components of bee venom (2.5 μg/mL). Moreover, suramin inhibited the in vivo myotoxicity induced by i.m. injection of A. mellifera venom in mice (0.5 μg/g). The analysis of the area under the plasma CK vs. time curve showed that preincubation, pre- and posttreatment with suramin (30 μg/g) inhibited bee venom myotoxic activity in mice by about 89%, 45% and 40%, respectively. Suramin markedly inhibited the PLA2 activity in a concentration-dependent way (1-30 μM). Being suramin a polyanion molecule, the effects observed may be due to the interaction of its charges with the polycation components present in A. mellifera bee venom.
authors.affiliation: Programa de Farmacologia e Química Medicinal, Instituto de Ciências Biomédicas, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Camila Z
authors.initials: CZ
authors.lastname: El-Kik
authors.forename: Fabrício F A
authors.initials: FF
authors.lastname: Fernandes
authors.forename: Marcelo Amorim
authors.initials: MA
authors.lastname: Tomaz
authors.forename: Glauco A
authors.initials: GA
authors.lastname: Gaban
authors.forename: Tatiane F
authors.initials: TF
authors.lastname: Fonseca
authors.forename: Sabrina
authors.initials: S
authors.lastname: Calil-Elias
authors.forename: Suellen D S
authors.initials: SD
authors.lastname: Oliveira
authors.forename: Claudia L M
authors.initials: CL
authors.lastname: Silva
authors.forename: Ana Maria Blanco
authors.initials: AM
authors.lastname: Martinez
authors.forename: Paulo A
authors.initials: PA
authors.lastname: Melo
mesh_terms: D000818:Animals; D000997:Antivenins / Q000494:pharmacology*; D001514:Bee Venoms / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects; D002478:Cells, Cultured; D003402:Creatine Kinase / Q000097:blood; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D004730:Endothelium, Vascular / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects; D005070:Evans Blue; D006400:Hematocrit; D007273:Injections, Intramuscular; D008136:Longevity / Q000187:drug effects; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000473:pathology; D054467:Phospholipases A2 / Q000378:metabolism; D051381:Rats; D012508:Sarcolemma / Q000187:drug effects / Q000201:enzymology; D012867:Skin / Q000098:blood supply; D013498:Suramin / Q000494:pharmacology*
chemical_list: D000997:Antivenins; D001514:Bee Venoms; D005070:Evans Blue; D013498:Suramin; D003402:Creatine Kinase; D054467:Phospholipases A2