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

BACKGROUND Severe 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. METHODS Wistar 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. RESULTS In 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. CONCLUSIONS Our 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.