title: Crotoxin is responsible for the long-lasting anti-inflammatory effect of Crotalus durissus terrificus snake venom: involvement of formyl peptide receptors.
abstract: In the present study, it was investigated which components are responsible for the anti-inflammatory properties of Crotalus durissus terrificus venom (CdtV). The effect of crotoxin, as well as of other CdtV components was evaluated on edema, cell migration and alterations in leukocyte-endothelium interactions induced by carrageenan. Crotoxin (40 microg kg(-1)) was injected at different time periods before or after the injection of carrageenan (15 mg kg(-1)) into the mouse hind paw, peritoneum or scrotum. Results showed that crotoxin, but not other CdtV components, significantly inhibited inflammatory edema and cell migration when administered before or after carrageenan injection in mice. This toxin also prevented the occurrence of alterations in leukocyte-endothelium interactions induced by carrageenan injection, such as the increase in adhered cells. In animals pretreated with Boc2 (a selective antagonist of formyl peptide receptors), crotoxin showed neither inhibitory effects on edema and cell migration, nor prevented alterations in leukocyte-endothelium interactions induced by carrageenan. These findings demonstrate that crotoxin is the component responsible for the long-lasting anti-inflammatory activity of crude C. durissus terrificus venom, and activation of formyl peptide receptors seems to play a major role in this effect.
authors.affiliation: Laboratório de Fisiopatologia, Instituto Butantan, São Paulo, Brazil.
authors.forename: F P B
authors.initials: FP
authors.lastname: Nunes
authors.forename: B C
authors.initials: BC
authors.lastname: Zychar
authors.forename: M S
authors.initials: MS
authors.lastname: Della-Casa
authors.forename: S C
authors.initials: SC
authors.lastname: Sampaio
authors.forename: L R C
authors.initials: LR
authors.lastname: Gonçalves
authors.forename: M C
authors.initials: MC
authors.lastname: Cirillo
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002351:Carrageenan / Q000633:toxicity; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D017839:Crotalus / Q000502:physiology*; D003439:Crotoxin / Q000494:pharmacology*; D004195:Disease Models, Animal; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D006614:Hindlimb; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy*; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008833:Microcirculation / Q000187:drug effects; D018482:Muscle, Skeletal / Q000098:blood supply; D010537:Peritoneum / Q000187:drug effects / Q000473:pathology; D044042:Receptors, Formyl Peptide / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D044042:Receptors, Formyl Peptide; D002351:Carrageenan; D003439:Crotoxin