RESUMO
In the present study, it was investigated which components are responsible for the antiinflammatory 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 leukocyteendothelium interactions induced by carrageenan. Crotoxin (40 mg 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 leukocyteendothelium interactions induced by carrageenaninjection, such as the increase in adhered cells. In animals pretreated with Boc2 (a selective antagonist of formyl peptide receptors), crotoxin showed neither inhibitoryeffects on edema and cell migration, nor prevented alterations in leukocyteendothelium interactions induced by carrageenan. These findings demonstrate that crotoxin is thecomponent 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 inthis effect.
Assuntos
Animais , Ratos , Crotalus cascavella , Crotoxina/antagonistas & inibidores , Crotoxina/efeitos adversos , Serpentes/classificação , Venenos de Serpentes/análise , Venenos de Serpentes/efeitos adversos , Venenos de Serpentes/toxicidade , Carragenina , Inflamação , Inflamação/diagnóstico , MicrocirculaçãoRESUMO
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.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Crotalus/fisiologia , Crotoxina/farmacologia , Edema/tratamento farmacológico , Inflamação/tratamento farmacológico , Receptores de Formil Peptídeo/efeitos dos fármacos , Animais , Carragenina/toxicidade , Movimento Celular/efeitos dos fármacos , Movimento Celular/fisiologia , Modelos Animais de Doenças , Edema/induzido quimicamente , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Membro Posterior , Inflamação/induzido quimicamente , Leucócitos/efeitos dos fármacos , Leucócitos/metabolismo , Masculino , Camundongos , Microcirculação/efeitos dos fármacos , Músculo Esquelético/irrigação sanguínea , Peritônio/efeitos dos fármacos , Peritônio/patologia , Receptores de Formil Peptídeo/metabolismoRESUMO
OBJECTIVE AND DESIGN: The present study investigates the supposed advantage of using an association of anti-inflammatory drugs and serum therapy to treat mouse paw edema induced by injection of Bothrops jararaca snake venom (BjV). MATERIAL AND METHODS: Edema was induced by injecting BjV (2 microg) into the footpad of male Swiss mice (20-25 g) and measured by plethysmography. Groups of mice were treated 15, 30 or 45 min after BjV injection with Bothrops antivenom or anti-inflammatory drugs (dexamethasone, indomethacin or zileuton), or with the association of antivenom and each one of these drugs. RESULTS: Antivenom, dexamethasone and indomethacin were effective in reducing the paw edema when used up to 30 min after BjV injection. Zileuton had the same effect, but only if used up to 15 min after BjV injection. The association of antivenom and dexamethasone showed the greatest inhibitory effect when used up to 45 min after BjV injection. At this time, antivenom or anti-inflammatory drugs administered alone were ineffective. CONCLUSION: Results suggest that dexamethasone combination with serum therapy can be beneficial for treatment of inflammatory edema caused by B. jararaca envenomation.
