Pattern of inflammatory response to Loxosceles intermedia venom in distinct mouse strains: A key element to understand skin lesions and dermonecrosis by poisoning

Ribeiro, Mara Fernandes; Oliveira, Felipe Leite de; Monteiro-Machado, Marcos; Cardoso, Priscilla Farinhas; Guilarducci-Ferraz, V.V.C.; Melo, Paulo A.; Souza, Cristina Maria Magalhães de; Calil-Elias, Sabrina

doi:10.1016/j.toxicon.2015.01.008

Cited by 7 publications

(5 citation statements)

References 63 publications

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“…Edema formation has also been observed for nontheraphosid spiders such as P. nigriventer (Antunes et al, 1992Bento et al, 1995;Costa et al, 1997) and Loxosceles spp. (Rattmann et al, 2008;Paludo et al, 2009;Barbaro et al, 2010;Guimarães et al, 2013;Ribeiro et al, 2015), and a variety of Australian spiders (Atkinson, 1986;Korszniak and Story, 1995). Unlike envenoming by Loxosceles spp.…”

Section: Discussionmentioning

confidence: 99%

Pharmacological Characterization of the Edema Caused by Vitalius dubius (Theraphosidae, Mygalomorphae) Spider Venom in Rats

Silva

Linardi

Antunes

et al. 2015

Journal of Pharmacology and Experimental Therapeutics

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Bites by tarantulas (Theraphosidae, Mygalomorphae) in humans can result in mild clinical manifestations such as local pain, erythema, and edema. Vitalius dubius is a medium-sized, nonaggressive theraphosid found in southeastern Brazil. In this work, we investigated the mediators involved in the plasma extravasation caused by V. dubius venom in rats. The venom caused dose-dependent (0.1-100 mg/site) edema in rat dorsal skin. This edema was significantly inhibited by butyl]benzamide) (SR48968, a neurokinin NK 2 receptor antagonist) had no effect on the venom-induced increase in vascular permeability. In rat hind paws, the venom-induced edema was attenuated by ketoprofen (a nonselective COX inhibitor) administered 15 minutes postvenom. Preincubation of venom with commercial antiarachnid antivenom attenuated the venom-induced edema. These results suggest that the enhanced vascular permeability evoked by V. dubius venom involves serotonin, COX products, neurokinin NK 1 receptors, and nitric oxide formation. The attenuation of hind paw edema by ketoprofen suggests that COX inhibitors could be useful in treating the local inflammatory response to bites by these spiders.

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Section: Discussionmentioning

confidence: 99%

Pharmacological Characterization of the Edema Caused by Vitalius dubius (Theraphosidae, Mygalomorphae) Spider Venom in Rats

Silva

Linardi

Antunes

et al. 2015

Journal of Pharmacology and Experimental Therapeutics

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“…A significant reduction of heterophils was shown after venom injection but not after treatment with copaiba oil. Diminution in the number of circulating heterophils after 24 hours may be related to an acute inflammatory response, considering that these cells are found at the injury site within a few hours after venom injection and are reduced in blood circulation after 24 hours, as also observed in mice [1]. Together, these results indicated a lesser migration of heterophils to the skin and possible protective effect associated with reduced heterophilic response after venom injection and treatment with copaiba oil.…”

Section: Discussionmentioning

confidence: 72%

“…The venom of spiders belonging to the genus Loxosceles produces a characteristic set of symptoms known as loxoscelism. Currently, loxoscelism has been hypothesized to be a multifactorial process involving a direct action of venom on the inflammatory response [1-6]. The main characteristic of envenomation is dermonecrosis at the bite site that is manifested initially by direct and degenerative effects of the venom components on the cell membrane, basement membrane, and extracellular matrix resulting in drastic tissue damage [7].…”

Section: Introductionmentioning

confidence: 99%

Effects of copaiba oil on dermonecrosis induced by Loxosceles intermedia venom

Ribeiro

Oliveira

Souza

et al. 2019

J. Venom. Anim. Toxins incl. Trop. Dis

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Background: Accidents caused by spiders of the genus Loxosceles constitute an important public health problem in Brazil. The venom of Loxosceles sp induces dermonecrosis at the bite site and systemic disease in severe cases. Traditional medicine based on plant-derived products has been proven to reduce the local effects of envenomation. The present study verified the healing effects of copaiba oil on lesions induced by the venom of L. intermedia. Methods: Cutaneous lesions were induced on the backs of rabbits by intradermal injection of L. intermedia venom. Copaiba oil was applied topically 6 hours after injection; the treatment was repeated for 30 days, after which animal skins were removed and processed for histopathological analysis. Blood samples were also collected before and 24 hours after venom inoculation to measure the hematological parameters. Results: Compared to the control group, the platelet count was reduced significantly in all groups inoculated with venom, accompanied by a decreased number of heterophils in the blood. The minimum necrotic dose (MND) was defined as 2.4 μg/kg. Topical treatment with copaiba oil demonstrated a differentiated healing profile: large skin lesions were observed 10 days after venom inoculation, whereas formation of a thick crust, without scarring was observed 30 days after venom inoculation. Histopathological analysis showed no significant difference after treatment. Nevertheless, the copaiba oil treatment induced a collagen distribution similar to control skin, in marked contrast to the group that received only the spider venom injection. Conclusions: We conclude that copaiba oil may interfere in the healing process and thus propose it as a possible topical treatment for cutaneous lesions induced by L. intermedia venom.

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“…Another characteristic of Loxosceles envenomation is the evolution of edema that is difficult to neutralize when only antisera against PLDs are used [35,77], probably due to the contribution of other toxins present in the venoms as well as the evolution of the inflammatory picture [78]. Regardless of other factors that may be involved, the anti-LgRec1ALP1 was able to neutralize 76, 40 and 54% of this activity elicited by L. gaucho , L. laeta , and L. intermedia venoms, respectively.…”

Section: Discussionmentioning

confidence: 99%

Design and Production of a Recombinant Hybrid Toxin to Raise Protective Antibodies against Loxosceles Spider Venom

Pal

Lhal

Colombini

et al. 2019

Toxins

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Human accidents with spiders of the genus Loxosceles are an important health problem affecting thousands of people worldwide. Patients evolve to severe local injuries and, in many cases, to systemic disturbances as acute renal failure, in which cases antivenoms are considered to be the most effective treatment. However, for antivenom production, the extraction of the venom used in the immunization process is laborious and the yield is very low. Thus, many groups have been exploring the use of recombinant Loxosceles toxins, particularly phospholipases D (PLDs), to produce the antivenom. Nonetheless, some important venom activities are not neutralized by anti-PLD antibodies. Astacin-like metalloproteases (ALMPs) are the second most expressed toxin acting on the extracellular matrix, indicating the importance of its inclusion in the antigen’s formulation to provide a better antivenom. Here we show the construction of a hybrid recombinant immunogen, called LgRec1ALP1, composed of hydrophilic regions of the PLD and the ALMP toxins from Loxosceles gaucho. Although the LgRec1ALP1 was expressed as inclusion bodies, it resulted in good yields and it was effective to produce neutralizing antibodies in mice. The antiserum neutralized fibrinogenolytic, platelet aggregation and dermonecrotic activities elicited by L. gaucho, L. laeta, and L. intermedia venoms, indicating that the hybrid recombinant antigen may be a valuable source for the production of protective antibodies against Loxosceles ssp. venoms. In addition, the hybrid recombinant toxin approach may enrich and expand the alternative antigens for antisera production for other venoms.

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Pattern of inflammatory response to Loxosceles intermedia venom in distinct mouse strains: A key element to understand skin lesions and dermonecrosis by poisoning

Cited by 7 publications

References 63 publications

Pharmacological Characterization of the Edema Caused by Vitalius dubius (Theraphosidae, Mygalomorphae) Spider Venom in Rats

Pharmacological Characterization of the Edema Caused by Vitalius dubius (Theraphosidae, Mygalomorphae) Spider Venom in Rats

Effects of copaiba oil on dermonecrosis induced by Loxosceles intermedia venom

Design and Production of a Recombinant Hybrid Toxin to Raise Protective Antibodies against Loxosceles Spider Venom

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