Determination of the sub-lethal nephrotoxic dose of Russell's viper (Daboia russelii) venom in Wistar rats

Acute kidney injury caused by venomous animals: inflammatory mechanisms

“…In their study, Tchaou et al [ 54 ] emphasize that viper venoms are liable for 15% envenomings and bring hemorrhagic and necrotizing complications involving several organs as well as direct toxic action of the venom on the renal parenchyma [ 54 ]. In Russel viper envenoming, acute kidney damage and nephrotoxic effects have been related to Russel’s viper venom (RVV7), which can cause hemodynamic changes and primary proximal and distal renal tubular degeneration [ 36 , 54 , 55 ]. In a cell culture study with proximal tubular cells, RVV-7 led to reduced cell viability, necrosis and increased LDH while basic protein isolated from RVV-7 might induce renal tubular necrosis in mice [ 56 ].…”

“…Likewise, thrombotic microangiopathy is expected to play a role in kidney damage from Russell’s viper bites. Despite the absence of arterial thrombosis, there were microthrombi in glomerular capillaries in some kidney samples from animals exposed to RVV7, thus suggesting thrombotic microangiopathy influence as evidence corroborating inflammatory and nephrotoxic process in AKI [ 55 ].…”

“…Venom inoculation has been demonstrated [ 22 , 55 ] to yield complex effects on sodium channels, especially altering electrolytes transport in renal tubules, leading to catecholamines and acetylcholine release (mediators causing serious manifestations due to parasympathetic or sympathetic effects) while intensifying tubular injury due to deleterious consequences from higher cytosolic Ca 2+ concentration. In scorpionic accidents, pro-inflammatory cytokines and mediators - including interleukins (ILs), tumor necrosis factor (TNFα), nitric oxide (NO), platelet aggregation factor (PAF), catecholamines, prostaglandins, kinins, leukotrienes, angiotensin (AII) and endothelin (ET) - become elevated [ 58 , 59 ].…”

“…Inflammatory environment, in turn, will largely increase Ripk3 and Mlkl genes in kidney due to hemoglobinuria; thus, necroptosis induction in cells will occur due to high concentration of venom, heme and expression of Tnf-α, Tlr-4, Ripk3 and Mlkl. In the experimental model used in [ 55 ], envenomed animals showed significant Tnf-α, Tlr-4, Ripk3 increases in groups exposed to 5 and 10 mg-venom/kg-body treatments. However, it was demonstrated that positive regulation is dose dependent, significantly increasing the damage according to the administered amount.…”

“…In scorpion sting, aforesaid mechanism results from large amounts of hemoproteins released in extracellular space where hemoglobin oxidation occurs. In turn, after hemolysis there might be high concentration of ferric Hb (Fe 3+ ), free heme group release and, thus, acceleratting the production of free radicals that accumulate in renal cortex, promoting toxic action [ 55 ].…”