(1) Experiments were performed in laboratory animals with Wistar rats (250 g) and CF-1 mice that received venoms from Micrurus fulvius and M. nigrocinctus. Parameters evaluated: lethality, coagulation changes, hemorrhagic process assessment, phospholipase activity, hemolysis, uremia, inflammation and edema, as well as histopathological analysis. |
To evaluate in vivo skeletal muscle changes and their association with renal lesions in rats intramuscularly injected with venom from different species of Micrurus from South, Central and North America. |
Kidneys of rats injected with either M. fulvius or M. nigrocinctus venoms exhibited nuclear fragmentation, edge destruction, basement membrane rupture and epithelial exfoliation of tubular cells, presence of granular changes and tubules thickening. Presence of abundant protein material and granular cylinders was evidenced in tubules of different nephron sections. Both glomerular congestion and intracapillary thrombi presence were observed in glomeruli of mice injected with these two venoms. |
Although renal lesions have not been described in clinical cases of Micrurus envenoming, the potential for nephrotoxicity of these venoms should be considered since the kidneys of animals exposed to M. fulvius or M. nigrocinctus venoms presented lesions consistent with extensive tubular necrosis, brush border destruction, basement membrane rupture and epithelial exfoliation of tubular cells, granular plaster and tubules thickening. |
(2) In this study, Swiss mice were the experimental model. Hematological changes, polarization of associated splenic T cells were analyzed in order to investigate the immune response to Russell viper venom (RVV) using acute kidney injury (AKI) induction model. |
To investigate the immune response to Russell viper venom in acute kidney injury induction model in a murine experimental model. |
In the group with acute kidney injury caused by snake venom, findings such as oliguria, urinary microprotein with significant elevation, decreased urinary creatinine and creatinine clearance were confirmed in comparison with the control group. Hematological analyzes revealed significant neutrophilic leukocytosis, favoring a state of acute inflammation in the group of acute kidney injury induced by snake venom (SAKI). The splenocyte immunophenotyping study showed a significant decrease in CD4 + / CD8 + ratio with a significant increase in the regulatory helper (CD25 + FoxP3 +) and cytotoxic subset of T cells. In addition, regulatory T cells in CD25-FoxP3 + reservoir were also found to be significantly elevated in the SAKI group compared to the control. |
Results from the present study clearly indicated a state of acute inflammation and polarization of splenic T cells towards the regulatory subset at the crest of SAKI. The findings of this research also support the concept of circulatory involvement and splenic inflammatory and immunological mediators in pathogenesis and/or repair phase of acute kidney injury induced by snake venom, which was otherwise attributed to the direct toxic effect of the venom. |
(3) In this study, Wistar rats received increasing doses of intraperitoneal Russell viper venom to investigate acute kidney injury (AKI) by measuring creatinine and examining renal histology. |
To investigate acute kidney injury (AKI) by measuring creatinine (1.5-fold increase in serum creatinine above baseline) and examining renal histology after administration of increasing doses of Russell viper venom. |
Increase in serum creatinine occurred only with 0.4 mg/kg venom dose; acute tubular necrosis, glomerular necrosis, cortical necrosis and interstitial inflammation were observed with venom doses ≥ 0.25 mg/kg. |
Despite widely used as standard biomarker for AKI diagnosis, serum creatinine is considered a delay and relatively sensitive biomarker for detecting kidney injury. The study confirmed an increase in serum creatinine significant enough to diagnose AKI that showed histological evidence of nephrotoxicity. In contrast, 5 out of 7 rats that demonstrated a significant increase in serum creatinine showed histological evidence of nephrotoxicity. |
(4) In vivo study used male Balb/c mice subcutaneously inoculated with H. lepturus venom. After 1 and 7 days, urinalysis, stereological evaluations and gene expression of Ngal, Tnf-α, Tlr-4, Ripk3, Mlkl and Acsl4 were performed. Analyzes were performed through real-time PCR. |
To evaluate the potential role of necroptosis and ferroptosis in AKI induced by H. lepturus. |
The study pointed that overloading in Ngal renal expression (nephrotoxicity biomarker) refers to overexpression of Tnf-α, Tlr-4, Ripk3 and Mlkl genes in kidneys treated with venom; it was also observed that malondialdehyde (MDA) level was increased in a dose-dependent manner similar to Acsl4 gene expression, thus suggesting a major role of ferroptosis in hemoglobinuria-mediated ARI after envenoming while increased transcription of Tlr-4 and Tnf-α receptor may cause phosphorylation of Ripk3-Mlkl complex, collapse of membrane potential and DAMPs release that intensified inflammation cytokines in the kidney. |
The study assumes that coexistence of two separate pathways of regulated necrosis and inflammatory environment provide a promising perspective in the prevention and treatment of hemoglobinuria-induced ARI after envenoming. Findings of this research revealed that AKI induced by hemoglobinuria is associated with the expression of inflammatory cytokines, renal cell death and overexpression of Ngal gene. This study emphasizes the role of immunogenic cell death attributable to regulated necrosis during venom-induced ARI. In this regard, prevention of regulated necrosis and inflammation seem beneficial for AKI treatment. |
(5) Wistar rats received L. obliqua venom; after the experiment, acute effects were observed after the administration of injected subcutaneous venom; biochemical, hematological, histopathological, myotoxic and genotoxic alterations were described. |
To understand systemic pathophysiological mechanisms of L. obliqua envenoming. |
Hematological findings were consistent with hemolytic anemia and neutrophilic leukocytosis. Histopathological changes were mainly related to hemorrhage and inflammation in subcutaneous tissue, lung, heart and kidneys. Myoglobin cylinders were also detected in renal tubules. Increased levels of creatine kinase and creatine kinase-MB were correlated with myocardial necrosis as observed in vivo and confirmed myotoxicity detected in vitro in isolated long extensor muscles of fingers. Significant DNA damage was observed in kidneys, heart, lung, liver and lymphocytes. |
Data reveal important biochemical, hematological and histopathological changes, suggesting damage occurrence to multiple organs, hemorrhagic disorders, AKI. The study demonstrated myotoxic, cardiotoxic and genotoxic activities. |
(6) In this study, L. obliqua venom was subcutaneously injected into Wistar rats and renal function was examined, besides morphological and biochemical parameters. |
To evaluate possible mechanisms involved in renal dysfunction pathogenesis due to L. obliqua envenoming. |
L. obliqua envenoming causes acute tubular necrosis, which is associated with renal inflammation; formation of hematic molds, resulting from intravascular hemolysis; increased vascular permeability and fibrosis. Envenomed kidneys increase the expression of proteins involved in cell stress, inflammation, tissue damage, heme-induced oxidative stress, coagulation and activation of the complement system. |
Mechanisms of L. obliqua-induced AKI are complex and involve mainly glomerular and tubular functional impairment and vascular changes. |