The role of dexamethasone in scorpion venom-induced deregulation of sodium and water transport in rat lungs

Abstract

BackgroundSevere scorpion envenomation can evolve to lung injury and, in some cases, death. The lung injury could be attributed to acute left ventricular failure and increased pulmonary vascular permeability secondary to the release of inflammatory mediators. In clinical practice, corticosteroids have been administered to reduce the early side effects of the anti-venom. We propose to study the effects of Tityus serrulatus venom and dexamethasone on pulmonary expression of sodium and water transporters, as well as on the inflammatory response.MethodsWistar rats were injected intraperitoneally with saline (control group), dexamethasone, and saline (2.0 mg/kg body weight—60 min before saline injection; dexamethasone + saline group), venom (T. serrulatus venom—3.8 mg/kg body weight), or dexamethasone and venom (2.0 mg/kg body weight—60 min before venom injection; dexamethasone + venom group). At 60 min after venom/saline injection, experiments were performed in ventilated and non-ventilated animals. We analyzed sodium transporters, water transporters, and Toll-like receptor 4 (TLR4) by Western blotting, macrophage infiltration by immunohistochemistry, and serum interleukin (IL) by cytokine assay.ResultsIn the lung tissue of non-ventilated envenomed animals, protein expression of the epithelial sodium channel alpha subunit (α-ENaC) and aquaporin 5 (AQP5) were markedly downregulated whereas that of the Na-K-2Cl cotransporter (NKCC1) and TLR4 was elevated although expression of the Na,K-ATPase alpha 1 subunit was unaffected. Dexamethasone protected protein expression of α-ENaC, NKCC1, and TLR4 but not that of AQP5. We found that IL-6, IL-10, and tumor necrosis factor alpha were elevated in the venom and dexamethasone + venom groups although CD68 expression in lung tissue was elevated only in the venom group. Among the ventilated animals, both envenomed groups presented hypotension at 50 min after injection, and the arterial oxygen tension/fraction of inspired oxygen ratio was lower at 60 min than at baseline.ConclusionsOur results suggest that T. serrulatus venom and dexamethasone both regulate sodium transport in the lung and that T serrulatus venom regulates sodium transport via the TLR4 pathway.

Cytokines and their regulators in rat lung following scorpion envenomation

“…Although the mechanisms by which the immune system detects venom components and initiates inflammation, as well as the signaling pathways that regulate the immune response, remain unknown, a number of studies indicates the implication of pattern recognition receptors (PRRs) located on innate immune system cells, such as Toll-like receptors (TLRs), in these processes. While TLRs are usually activated by ligands of bacterial or viral origin (pathogen-associated molecular patterns) or by endogenous compounds (damage-associated molecular patterns), recent studies indicate that TLR2 and TLR4 can also recognize non-microbial ligands, including certain venom components (so-called venom-associated molecular patterns) with following stimulation of pro-inflammatory pathways ( Martin-Eauclaire et al, 2019 ; Malaque et al, 2015 ; Reis et al, 2019 ). For instance, it was found that T. serrulatus venom, interacting with TLR2, TLR4 and CD14 of macrophages, activates these cells and through NF-κB- and AP-1-dependent signaling pathways promote them to generate the cytokines and lipid mediators ( Ryan et al, 2021 ; Zoccal et al, 2019 ).…”

Clinical manifestations and management of Tityus species envenoming: A systematic review

“…However, other studies demonstrate that dexamethasone doesn't have any benefits in the management of scorpion sting (Bahloul et al, 2013;Malaque et al, 2015).…”

Scorpion Stings in Minas Gerais (Brazil): A Monocentric Retrospective Study Evaluating All Envenoming Cases of Local Scorpionism

“…Unlike the results of other studies, corticosteroids have not shown any benefit in the management of scorpion stings. [42][43][44]…”