Thalassophryne nattereri(niquim): from toxins to therapy

Lopes-Ferreira, M.(1)

(1)Laboratório de Imunopatologia do Instituto Butantan, São Paulo, Brasil

The accidents caused by the fish T. nattereri represent a serious medical, economic and social problem in the North and Northeast of Brazil. The venom induces severe edema and pain followed by a fast settling necrosis, both in human victims and experimental models. Analysis of its local effects showed a myotoxic effect with muscle damage and difficult regeneration. Blood flow at microvessels was also impaired with stasis concomitantly with the presence of thrombi in venules, focal transient constrictions in arterioles, and increase in vascular permeability. Venom action was locally restricted and no alteration on systemic blood coagulation was observed. Venom lacked a direct pro-coagulant activity but exerted a strong cytolytic effect on platelets and endothelial cells in vitro. Local inflammatory response was discrete since T. nattereri venom stimulate the release of low levels of IL-1b, IL-6 and TNF-a cytokines, and diminished infiltrate of cells was observed in damaged tissue 24 hours after injection. The mechanisms involved in venom action were evaluated. Nociceptive and edematogenous activities were not reduced neither by treatment with inhibitors of serotonin and histamine nor by non-steroidal and steroidal anti-inflammatory drugs, but by the administration of a kallikrein specific inhibitor demonstrating that tissue kallikrein-dependent pathways are involved in local effects. The toxin responsible for T. nattereri venom effects was characterized as a 48 kDa fraction, able to convert LMW kininogen into Lys-BK, in a metal-dependent proteolysis. T. nattereri antivenom produced in horses was able to recognize all venom bands including the 48 kDa fraction and neutralized venom-induced edema, nociception and necrosis in experimental models. These results indicate that the use of serumtherapy possibly associated with local administration of kalikrein inhibitors is a promising treatment for accidents caused by the fish T. nattereri.

Financial support: FAPESP (01/02937-2)

CORRESPONDENCE TO:

Lopes-Ferreira, M. Laboratório de Imunopatologia do Instituto Butantan, Av Vital Brasil, 1500, 05503-900, São Paulo, SP, Brasil. E.mail: mlferrei@usp.br