Brain, liver and kidney lesions associated with Loxosceles intermedia envenomation in guinea pigs

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DOI:

https://doi.org/10.1590/1809-6891v26e-83255E

Abstract

The venom of Loxosceles spiders is characterized by a complex protein composition, which underlies the clinical condition known as loxoscelism. This syndrome is characterized mainly by gravitational spreading dermonecrotic lesions, but also, in rare cases, it can involve severe systemic complications, such as renal failure and hematological disorders. Although the pathophysiological mechanism of cutaneous loxoscelism is widely investigated, the neurological manifestations associated with the venom are rare and poorly researched. The present study aimed to investigate the histopathological alterations in guinea pigs' (Cavia porcellus) liver, kidney, and central nervous system (CNS) inoculated with Loxosceles intermedia venom. Sixteen guinea pigs were challenged with venom doses ranging from 11.627 to 350 μg/animal intradermally in the intrascapular region, while two additional animals were used as controls, receiving only 0.9 % saline solution in the same application region. Microscopic evaluation of hepatic and renal tissues demonstrated hepatic necrosis and acute renal tubular necrosis, respectively. In the CNS, lesions compatible with lymphoplasmacytic and histiocytic encephalitis, moderate focal gliosis, and neutrophilic margination in certain regions of the brain were identified. These neurological findings in guinea pigs exposed to L. intermedia venom are unprecedented, providing new evidence of CNS susceptibility to Loxosceles venom.
Keywords: brown spider; loxoscelic venom; central nervous system; encephalitis; loxoscelism.

Keywords: brown spider, loxoscelic venom, central nervous system, encephalitis, loxoscelism.

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Author Biography

Ana Flávia Machado Botelho, Universidade Federal de Goiás (UFG), Goiânia, Goiás, Brazil

Possui graduação em Medicina Veterinária pela Universidade Federal de Minas Gerais (2009-2013), mestrado (2014-2015) e doutorado (2016-2018) em Ciência Animal pela UFMG, na subárea de Toxicologia e Plantas Tóxicas. Professora Adjunta de Toxicologia da Universidade Federal de Goiás. Tem experiência na área de Medicina Veterinária, com ênfase em Toxicologia Veterinária, Patologia Veterinária e Cardiologia Animal. Email: anaflaviamabo@gmail.com.br

References

World Spider Catalog. Version 25.5 [internet]. Bern: Natural History Museum Bern; 2025 [updated 2024 December 24; cited 2025 Jan 22]. Available from: http://wsc.nmbe.ch, accessed on Jan 22. doi: 10.24436/2

Secretaria Municipal de Saúde de São José dos Pinhais. Guia de araneísmo: guia de vigilância em saúde [Internet]. São José dos Pinhais (PR): Secretaria Municipal de Saúde; 2024 [cited 2025 set 25]. Available from: https://www.sjp.pr.gov.br/wp-content/uploads/2024/07/ARANEISMO-GUIA-DE-VIGILANCIA-EM-SAUDE.pdf

Futrell JM. Loxoscelism. Am J Med Sci. 1992;304(4):261-7. doi: http://dx.doi.org/10.1097/00000441-199210000-00008

Binford GJ, Callahan MS, Bodner MR, Rynerson MR, Núñez PB, Ellison CE, et al. Phylogenetic relationships of Loxosceles and Sicarius spiders are consistent with Western Gondwanan vicariance. Mol Phylogenet Evol. 2008;49(2):538-53. Available from: http://dx.doi.org/10.1016/j.ympev.2008.08.003

Gremski LH, Matsubara FH, da Justa HC, Schemczssen-Graeff Z, Baldissera AB, Schluga PHC, et al. Brown spider venom toxins: what are the functions of astacins, serine proteases, hyaluronidases, allergens, TCTP, serpins and knottins? J Venom Anim Toxins Incl Trop Dis. 2021;27:e20200188. Available from: http://dx.doi.org/10.1590/1678-9199-JVATITD-2020-0188

Rodrigues GM, de Almeida ME, Marcelino SAC, Fernandes PBU, da Cruz JOP, Araújo FL, et al. Protective effects of mesenchymal stromal cell-derived secretome on dermonecrosis induced in rabbits by Loxosceles intermedia spider venom. J Venom Anim Toxins Incl Trop Dis. 2024;30:e20240004. Available from: http://dx.doi.org/10.1590/1678-9199-JVATITD-2024-0004

Luciano MN, da Silva PH, Chaim OM, dos Santos VL, Franco CR, Soares MF, et al. Experimental evidence for a direct cytotoxicity of Loxosceles intermedia (brown spider) venom in renal tissue. J Histochem Cytochem. 2004;52(4):455-67. Available from: http://dx.doi.org/10.1177/002215540405200404

Soape MP, Swaminath D, Whealy M, Desai V. Ischemic brain injury secondary to severe systemic loxoscelism. Southwest Respir Crit Care Chron. 2014;2(6):45-8. Available from: http://dx.doi.org/10.12746/swrccc2014.0206.076

Mantopoulos D, Hendershot AJ, Cebulla CM, Hirsh DK. Bilateral optic neuropathy following bite from brown recluse spider (Loxosceles reclusa). Cutan Ocul Toxicol. 2016;35(2):168-72. Available from: http://dx.doi.org/10.3109/15569527.2015.1027906

Barbaro KC, Ferreira ML, Cardoso DF, Eickstedt VR, Mota I. Identification and neutralization of biological activities in the venoms of Loxosceles spiders. Braz J Med Biol Res. 1996 Nov;29(11):1491-7. PMID: 9196551.

Isbister GK, Fan HW. Spider bite. Lancet. 2011;378(9808):2039-47. Available from: http://dx.doi.org/10.1016/S0140-6736(10)62230-1

Gomez HF, Greenfield DM, Miller MJ, Warren JS. Direct correlation between diffusion of Loxosceles reclusa venom and extent of dermal inflammation. Acad Emerg Med. 2001;8(4):309-14. Available from: http://dx.doi.org/10.1111/j.1553-2712.2001.tb02107.x

de Oliveira CA, de Oliveira A, Chaim OM, Lugarini D, Bastos PAL, Paludo KS, et al. Effects of the venom and the dermonecrotic toxin LiRecDT1 of Loxosceles intermedia in the rat liver. Toxicon. 2008;52(6):695-04. Available from: http://dx.doi.org/10.1016/j.toxicon.2008.08.001

Okamoto CK, van den Berg CW, Masashi M, Gonçalves-de-Andrade RM, Tambourgi DV. Tetracycline reduces kidney damage induced by Loxosceles spider venom. Toxins. 2017;9(3):90. Available from: http://dx.doi.org/10.3390/toxins9030090

Ribeiro MF, Oliveira FL, Monteiro-Machado M, Cardoso PF, Guilarducci-Ferraz VV, Melo PA, et al. Pattern of inflammatory response to Loxosceles intermedia venom in distinct mouse strains: a key element to understand skin lesions and dermonecrosis by poisoning. Toxicon. 2015;96:10-23. Available from: http://dx.doi.org/10.1016/j.toxicon.2015.01.008

Gremski LH, da Justa HC, Polli NLC, Schluga PHC, Theodoro JL, Wille ACM, Senff-Ribeiro A, Veiga SS. Systemic loxoscelism, less frequent but more deadly: the involvement of phospholipases D in the pathophysiology of envenomation. Toxins (Basel). 2023 Jan;15(1):17. doi: http://dx.doi.org/10.3390/toxins15010017. PMID: 36672992; PMCID: PMC9861772

Valenzuela Córdova R, Rivera Estrella D, Bernardo JF, Jiménez D, Rodríguez Tudero C, Elías R, De La Flor JC. Hemoadsorption in multiorgan failure due to viscerocutaneous loxoscelism. Medicina (Kaunas). 2025 Jan;61(1):143. doi: http://dx.doi.org/10.3390/medicina61010143. PMID: 39962192; PMCID: PMC1176685

Lucato RV, Abdulkader RCRM, Barbaro KC, Mendes-Glória GE, Castro I, Baptista MASF, Cury-Patrício PM, Malheiros DMC, Schor N, Yu L, et al. Loxosceles gaucho venom-induced acute kidney injury: in vivo and in vitro studies. PLoS Negl Trop Dis. 2011;5(5):e1182. doi: http://dx.doi.org/10.1371/journal.pntd.0001182. PMID: 21655347; PMCID: PMC3104955

Golay V, Desai A, Hossain A, Roychowdhary A, Pandey R. Acute kidney injury with pigment nephropathy following spider bite: a rarely reported entity in India. Ren Fail. 2013;35(4):538-40. doi: https://doi.org/10.3109/0886022x.2013.768936. PMID: 23360344

Chaim OM, Sade YB, da Silveira RB, Toma L, Kalapothakis E, Chávez-Olórtegui C, Mangili OC, Gremski W, von Dietrich CP, Nader HB, Sanches Veiga S. Brown spider dermonecrotic toxin directly induces nephrotoxicity. Toxicol Appl Pharmacol. 2006 Feb 15;211(1):64-77. doi: http://dx.doi.org/10.1016/j.taap.2005.05.015. PMID: 16005484.

Dias-Lopes C, Felicori L, Guimarães G, Gomes ER, Roman-Campos D, Duarte H, Damasceno D, Martins M, Kalapothakis E, Almeida AP, Granier C, Cruz JS, Guatimosim S, Chávez-Olórtegui C. Cardiotoxic effects of Loxosceles intermedia spider venom and the recombinant venom toxin rLiD1. Toxicon. 2010 Dec;56(8):1426-35. doi: http://dx.doi.org/10.1016/j.toxicon.2010.08.008. PMID: 20727874

Cristina Vann T, Waller SB, Tavares Barwaldt E, Fiorini Telli S, Lopes Zibetti F, Priscila Vogt M, et al. Envenomation by Brown Spider (Loxosceles sp.) in a German Shepherd Bitch - Laboratory and Anatomopathological Findings: Acidente em cão Pastor Alemão por aranha-marrom. Acta Scientiae Vet. [Internet]. 2024 Aug. 6 [cited 2025 Sep. 25];52. Available from: https://seer.ufrgs.br/index.php/ActaScientiaeVeterinariae/article/view/139389

Babcock JL, Suber RL, Frith CH, Geren CR. Systemic effect in mice or venom apparatus extract and toxin from the brown recluse spider (Loxosceles reclusa). Toxicon. 1981;19(4):463-71. Available from: http://dx.doi.org/10.1016/0041-0101(81)90004-0

Plenge-Tellechea LF, Hernández-Ramos ÁD, Muñoz JM, Barraza-Garza G, Rico-Escobar E, Meléndez-Martínez D. Acanthocytosis and brain damage in area postrema and choroid plexus: Description of novel signs of Loxosceles apachea envenomation in rats. PLoS One. 2019;14(2):e0211689. Available from: http://dx.doi.org/10.1371/journal.pone.0211689

Published

2025-10-14

How to Cite

FERNANDES, Paula Bretas Ullmann; ARAÚJO, Matheus Dias; FRANÇA, Anna Paula Botelho; CHÁVEZ-OLÓRTEGUI, Carlos Delfin; SANTOS, Renato de Lima; BOTELHO, Ana Flávia Machado; MELO, Marília Martins. Brain, liver and kidney lesions associated with Loxosceles intermedia envenomation in guinea pigs. Brazilian Animal Science/ Ciência Animal Brasileira, Goiânia, v. 26, 2025. DOI: 10.1590/1809-6891v26e-83255E. Disponível em: https://revistas.ufg.br/vet/article/view/83255. Acesso em: 6 dec. 2025.

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Section

VETERINARY MEDICINE

Data statement

  • The research data is contained in the manuscript