Systemic response induced by Scorpaena plumieri fish venom initiates acute lung injury in mice☆
Introduction
Although venomous fish envenomations are less documented in Brazil than snake bites, some venomous species have been found. Here, special attention has been given to the venomous fish Thallasophryne nattereri, which provoke symptoms in fishermen and swimmers characterized by local pain and swelling, erythema, followed by intense necrosis that persists for several days (Fonseca and Lopes-Ferreirra, 2000). Murine models, which mimic the local manifestations of envenoming induced by T. nattereri, are used and show that low doses of the venom (0.3 μg/animal) induced local effects such as nociception and edema, similar to that described in humans (Lopes-Ferreira et al., 1998) and inflammatory response in footpad with cytokines such as TNF-α, IL-1β and IL-6 and a weak leukocyte influx (Lima et al., 2003). In addition, the venoms of the catfish Cathorops spixii or stingrays Potamotrygon cf. scobina and Potamotrygon gr. orbignyi induce local effects in mice mainly nociception and edema with moderate duration (Junqueira et al., 2007; Magalhaes et al., 2006).
The family Scorpaenidae represents a wide array of fish characterized by the ability to envenomate with various types of specialized spines (Kizer et al., 1985). This family includes the three genus: Synanceja, Scorpaena and Pterois. In a documented case Lehmann and Hardy (1993) described human envenomation by stonefish with pulmonary edema, developing within 35 min of envenomation that was confirmed radiographically. Wiener (1959) reported that injection of the venom from Synanceja trachynis into several animal species produced evidence of increased vascular permeability. In particular, acute pulmonary edema was observed in mice that were given the venom by intravenous injection.
Only members of the genus Scorpaena are found on the Brazilian coast, with Scorpaena plumieri being the most abundant specie found. The venomous apparatuses are composed of 13 dorsal, 3 anal and 2 pelvic short and thick spines with larger venom glands. The bizarrely shaped fish is often taken for a weed-covered stone, and accidents occur when swimmers, divers or fishermen step on the spines of the dorsal fin (Halstead, 1951; Roche and Halstead, 1972). After compression of the venom glands located at the base of the spines, venom travels from the glands through anterolateral depressions in the spines and into the wound. Symptoms are limited to severe local manifestations in the extremity involved (Haddad et al., 2003), and cardiotoxic and hypotensive effects induced in rats by this venom has been studied (Carrijo et al., 2005). The intensity of clinical features of S. plumieri envenomation is related to the concentration of venom injected in one or more puncture wounds. Patients can be stung by one or all spines present in the dorsal region of the fish, and each spine contains 5–10 mg of venom (Gwee et al., 1994).
The main objective of this study was to determine whether the injection of S. plumieri venom results in systemic response in mice, and whether this event initiates acute lung injury. Venom of S. plumieri was administered by an intraplantar or an intraperitoneal (i.p.) route in BALB/c mice, and remote lung injury was assessed by histopathology, increase of vascular permeability, neutrophil influx and production of the pro-inflammatory mediators such as IL-6, KC and MMPs, and the contribution of alveolar macrophages (AMs) was investigated.
Section snippets
Venom
Venom was obtained from specimens of S. plumieri (Fig. 1) collected in the coastal State of Espírito Santo, Brazil. The venom extraction was carried out according to Schaeffer et al. (1971). Protein content was determined by the colorimetric method of Bradford (1970) using bovine serum albumin (Sigma) as standard protein.
SDS–Polyacrylamide gel electrophoresis (SDS–PAGE)
The proteins (10 μg) of S. plumieri venom were analyzed by SDS–PAGE under non-reducing conditions by Laemmli (1970) using 12% gel and stained with silver. A pre-stained protein
Protein profile of S. plumieri venom
To verify the eletrophoretical profile, the venom was submitted to 12% SDS–PAGE (10 μg of protein/well). S. plumieri venom presented nine important bands: one band located above 116 kDa, one band located above 66, two bands located between 45 to 66 kDa, one band located at 45 kDa, another located below 45 kDa, two located below 35 kDa and the last one located at 25 kDa (Fig. 1C).
Effect of S. plumieri venom on BAL protein, leukocyte recruitment and pro-inflammatory mediator production in lungs
As a functional measurement of alveolar epithelial disruption, we measured total protein in BAL fluids. Between 2 and 24 h
Discussion
In humans, acute lung injury is characterized by epithelial and endothelial injury, neutrophilic alveolitis, and hyaline membrane formation. Neutrophil activation lead to the accumulation of oxidants and proteases in the lungs, which damage the cells of the alveolar environment. Scorpaena plumieri venomous fish inflicted severe injuries in humans characterized by systemic effects and cardiovascular abnormalities. Although cardiotoxic and hypotensive effects induced in rats by this venom have
Acknowledgments
This work was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) and CNPq.
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Ethical statement: All experiments are in accordance with the guidelines provided by the Brazilian College of Animal Experimentation, and were authorized by the Ethics Committee for Animal Research of the Butantan Institute (275/06).