Abstract
Acute renal failure (ARF) wich is one of the most serious complications of Bothrops snakebites, is one of the main causes of death and consequences for victims. However, its pathogenesis remains unclear. Considering that isolated toxins are relevant tools for understanding the actions of the whole venom, we studied properties of phospholipases A2 (Asp‐49 and Lys‐49) isolated from Bothrops pauloensis (from State of São Paulo, Southeast region of Brazil), on isolated perfused kidney of rat. The control group perfused with modified Krebs–Henseleit solution alone. The PLA2s (3μg/mL) caused significant effects in isolated rat kidney, Asp‐49 reducing perfusion pressure(PP), the Renal Vascular Resistence (RVR), the Urinary Flow (UF), the Glomerular Filtration Rate (GFR) and the percentage of tubular sodium (%TNa+), chloride (%TCl−) and potassium (%TK+). The Lys‐49 increased PP and UF and decreased the RFG and the %TNa+, %TK+ and %TCl‐. Oxidative stress in kidney tissue was evaluated by TBARS (thiobarbituric acid reactive substances), Nitrite and reduced Glutathione (GSH) level measurement. A significant increase was observed in TBARS (Lys‐49) and Nitrito (Asp‐49 and Lys‐49) and a decrease in GSH levels (Asp‐49) and increase (Lys‐49). The levels of inflammatory cytokines were measured. We analized the inflammatory cytokines, pro‐inflammatory interleukin 1 (IL‐1), tumor necrosis factor‐α (TNF‐α) and anti‐inflammatory interleukin 10 (IL‐10). The results showed high levels of both cytokines (by Lys‐49) and incresed TNF‐α and IL‐10 by Asp‐49. Increased TBARS, Nitrito level and decreased of GSH activity might be implicated in the presence of oxidative stress in patients with snake bite envenomation. These findings demonstrated that PLA2s caused nephrotoxicity in isolated kidney. The characterization of the effects in the isolated kidney gives strong evidences that the acute renal failure induced by these PLA2s is a result of the direct nephrotoxicity which may involve oxidative and inflammatory mechanisms.Support or Funding InformationCAPES, CNPq, UFC.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
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