Loxosceles venom-induced cytokine activation, hemolysis, and acute kidney injury

Souza, Alexandre Leite de; Málaque, Ceila Maria Sant’Ana; Sztajnbok, Jaques; Romano, Carla Cristina; Duarte, Ana Maria Ribeiro de Castro; Seguro, Antônio Carlos

doi:10.1016/j.toxicon.2007.08.011

Cited by 49 publications

(35 citation statements)

References 13 publications

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“…83 Bites by Loxosceles are associated with hemolysis, rhabdomyolysis, coagulopathy and AKI. 84,86,87 Glomerulonephritis has also been reported r e v i e w after Loxosceles bite, although a definite causeeffect relationship could not be established. 88 Latrodectus bite causes cardiovascular failure, arterial hypertension, myocardial damage, rhabdomyolysis, compartment syndrome and renal dysfunction.…”

Section: Presentationmentioning

confidence: 99%

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Animal toxins and the kidney

Sitprija

2008

Nat Rev Nephrol

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Envenomation or poisoning by toxins from animals poses an important health hazard in the tropics. Animal toxins are complex mixtures of proteins, peptides, enzymes and chemicals. These toxins exert their effects through modulation of ion channels and receptors, and via direct enzyme action. Depolarization or hyperpolarization of ion channels--caused by most marine toxins, and some snake and insect venoms--results in neuromuscular symptoms that can be associated with hemodynamic changes. Toxin enzymes, especially proteases and phospholipase A2, initiate inflammatory processes that involve the generation of proinflammatory cytokines and vasoactive mediators, resulting in systemic and renal hemodynamic alterations. Toxin enzymes also have direct effects on erythrocytes, myocytes, blood coagulation factors, vascular endothelium and epithelial cells. As a result, disseminated intravascular coagulation, bleeding diathesis, intravascular hemolysis and rhabdomyolysis are common after exposure to animal toxins. The renal manifestations of animal toxin envenomation, which are usually acute, result mainly from these enzymatic effects. All renal structures can be affected by animal toxins, and tubular necrosis is common. Acute kidney injury is attributed to decreased renal blood flow (associated with intravascular hemolysis or rhabdomyolysis), disseminated intravascular coagulation or direct tubular toxicity. Immunologic mechanisms have a minor role in the pathophysiology of nephropathy caused by animal toxins.

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Section: Presentationmentioning

confidence: 99%

“…Release of these molecules is triggered by phospholipase D and the proteases in the toxin and by the effects of the toxin on ion channels. 84 Rhabdomyolysis, myocardial damage, compartment syndrome and intravascular hemolysis further contribute to the renal dysfunction.…”

Section: Presentationmentioning

confidence: 99%

Animal toxins and the kidney

Sitprija

2008

Nat Rev Nephrol

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“…These studies demonstrated an important leukocytosis and neutrophilia presence, increasing in patients until two weeks after poisoning [30]. In addition, some patients displayed marked leukocytosis and IL-6 and TNF-α production in plasma [31]. …”

Section: Discussionmentioning

confidence: 99%

Phospholipase D from Loxosceles laeta Spider Venom Induces IL-6, IL-8, CXCL1/GRO-α, and CCL2/MCP-1 Production in Human Skin Fibroblasts and Stimulates Monocytes Migration

Rojas

Arán-Sekul

Cortés

et al. 2017

Toxins

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Cutaneous loxoscelism envenomation by Loxosceles spiders is characterized by the development of a dermonecrotic lesion, strong inflammatory response, the production of pro-inflammatory mediators, and leukocyte migration to the bite site. The role of phospholipase D (PLD) from Loxosceles in the recruitment and migration of monocytes to the envenomation site has not yet been described. This study reports on the expression and production profiles of cytokines and chemokines in human skin fibroblasts treated with catalytically active and inactive recombinant PLDs from Loxosceles laeta (rLlPLD) and lipid inflammatory mediators ceramide 1-phosphate (C1P) and lysophosphatidic acid (LPA), and the evaluation of their roles in monocyte migration. Recombinant rLlPLD1 (active) and rLlPLD2 (inactive) isoforms induce interleukin (IL)-6, IL-8, CXCL1/GRO-α, and CCL2/monocyte chemoattractant protein-1 (MCP-1) expression and secretion in fibroblasts. Meanwhile, C1P and LPA only exhibited a minor effect on the expression and secretion of these cytokines and chemokines. Moreover, neutralization of both enzymes with anti-rLlPLD1 antibodies completely inhibited the secretion of these cytokines and chemokines. Importantly, conditioned media from fibroblasts, treated with rLlPLDs, stimulated the transmigration of THP-1 monocytes. Our data demonstrate the direct role of PLDs in chemotactic mediator synthesis for monocytes in human skin fibroblasts and indicate that inflammatory processes play an important role during loxoscelism.

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“…Rhabdomyolysis has been reported following envenomation by insects of the Order Hymenoptera, including hornets, wasps, honey bees, and fire ants with clinically significant rhabdomyolysis being reported only following multiple stings [50][51][52][53][54]. Rhabdomyolysis has been rarely reported with spider envenomation including that of the genera Latrodectus and Loxosceles [55][56][57]. Other envenomations that may rarely involve rhabdomyolysis include the scorpions of genus Centruroides and the centipede Scolopendra heros [58,59].…”

Section: What Other Xenobiotics Cause Rhabdomyolysis?mentioning

confidence: 99%

Case Files of the Medical Toxicology Fellowship at Drexel University

Vearrier

Curtis

2011

J. Med. Toxicol.

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A 28-year-old female was brought to the emergency department (ED) by her roommate after a suicide attempt, in which the patient took 29 capsules of an over-the-counter (OTC) sleep aid containing 50 mg of diphenhydramine (DPH) per capsule, for a total of 1450 mg, and consumed 100 ml of vodka. Her weight was 67 kg, yielding a dose of 22 mg/kg DPH. When a roommate arrived home from work several hours later, he noticed that the patient was walking aimlessly through the house and that "she was out of it." The patient subsequently informed the roommate of her suicide attempt, at which point he brought her by car to our ED. According to the patient, the ingestion occurred 9 h prior to arrival.In the ED, the patient complained of bilateral tingling and numbness in her legs and feet that had started within the last 4 h. She had a subjective sensation of inability to control the muscles in her legs and leg weakness. The patient denied any history of leg trauma, recent strenuous physical activity, or recent prolonged inactivity. Her medical history was significant for cervical dysplasia status post surgical excision and major depressive disorder. The patient denied taking any other prescribed or OTC medications, which her roommate corroborated.Physical examination revealed a young, disheveled female with normal body habitus. Initial vital signs included a temperature of 36.4°C, heart rate 123 beats/ min, respiratory rate 18 breaths/min, blood pressure 112/ 83 mm Hg, and pulse oximetry of 98% on room air. Pupils were 6 mm bilaterally and sluggishly reactive to light. Extraocular movements were intact. The mucous membranes of the oropharynx were dry. Cardiac examination was significant for a regular tachycardia, while the pulmonary examination was normal. Abdominal examination was significant for bowel sounds being present but decreased. The patient was alert and oriented to self and place, but not to time. She was able to answer simple questions, but was slow to respond. Strength, sensation, and deep tendon reflexes were normal. No ataxia or tremor was present. Extremity examination was significant for mottled skin color on the anterior legs bilaterally. Dorsalis pedis and posterior tibialis pulses were normal, as was sensation, strength, and capillary refill throughout the bilateral lower extremities. What is the Pharmacology of DPH?DPH is a first-generation H 1 antihistamine. It belongs to the ethanolamine subclass of antihistamines along with carbinoxamine, clemastine, dimenhydrinate, and doxylamine. Histamine receptors are categorized into four subtypes This case report was presented in poster form at the EAPCCT conference in 2009 in Stockholm, Sweden.

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Loxosceles venom-induced cytokine activation, hemolysis, and acute kidney injury

Cited by 49 publications

References 13 publications

Animal toxins and the kidney

Animal toxins and the kidney

Phospholipase D from Loxosceles laeta Spider Venom Induces IL-6, IL-8, CXCL1/GRO-α, and CCL2/MCP-1 Production in Human Skin Fibroblasts and Stimulates Monocytes Migration

Case Files of the Medical Toxicology Fellowship at Drexel University

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