Revisiting the acute kidney injury in Wistar rats experimentally envenomated with Bothrops jararacussu venom

• Published in: Toxicon (Oxford) Vol. 199; pp. 117 - 126
• Main Authors: Romanelli, Mayara A., Soeiro, Paula A., Silva, Raquel Costa da, Taveira-da-Silva, Rosilane, Melo, Paulo A., Lara, Lucienne S.
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01-08-2021
• Subjects: Glomerular filtration rate; Preclinical model; Proteinuria; Routes of snake venom administration; Tubular injury; Routes of snake venom administration; Tubular injury; Glomerular filtration rate; Preclinical model; Proteinuria
• ISSN: 0041-0101; 1879-3150
• DOI: 10.1016/j.toxicon.2021.06.004

There is no consensus on whether serotherapy prevents acute kidney injury (AKI) and there is no pharmacotherapy to impede the disease. We aimed to elaborate an AKI model induced by the administration of Bothrops jararacussu (Bj) venom for preclinical studies. Male Wistar rats were randomly divided into 3 different groups: (1) Bj-IV: intravenous administration of 0.4 mg/kg Bj; (2) Bj-IP: intraperitoneal administration of 2.0 mg/kg Bj; (3) Bj-IM: intramuscular administration of 3.5 mg/kg Bj. For each corresponding control group, a 0.9% saline solution was administered. Kidneys, blood and urine samples were collected 24 or 72 h after administration of the Bj venom for renal function analysis. The IV- and IP-Bj groups presented a moderate tubular injury (score 3) and a time-dependent kidney dysfunction. In the Bj-IM group, renal tubular injury was aggravated (score 4) with collagen deposition and renal dysfunction was observed in the first 24 h: hyperfiltration, proteinuria, albuminuria and decreased fractional sodium excretion (FENa), regardless of the administered dose. Over time, the glomerular lesion was intensified, with a decrease in glomerular filtration rate (GFR; 67%), blood urea-nitrogen (BUN; 68%) and urine volume decrease (71%). Proteinuria and tubular function returned to control levels after 72 h. We attributed the pronounced kidney injury and reduced filtration function in the Bj-IM to the muscle damage provoked by the IM administration. We concluded that the Bj-IM is the best preclinical model of AKI with the monitoring of the progression of renal function in the periods of 24 and 72 h.
•Bothrops jararacussu (Bj) venom provokes kidney injury and impaired renal function despite of the route of administration.•The IV and IP routes presented a moderate and a time-dependent kidney dysfunction.•In the IM route renal tubular injury was aggravated with collagen deposition.•Hyperfiltration, proteinuria and decreased FENa occurs in the first 24 h.•AKI is sustained at 72 h, as determined by BUN accumulation and decreased GFR.