Effects of Lansberg’s Hognose Pit Vipers (Porthidium lansbergii hutmanni) Venom on Renal Ultrastructure in Experimental Mice

Ano: 2011 | Volume: 39 | Número: 1

Autores: Alba Vargas, Héctor Finol, María Girón, Héctor Scannone, Irma Fernández, Alexis RODRIGUEZ-ACOSTA

Palavras-chave: envenoming, glomeruli, kidney, porthidium lansbergii hutmanni, proximal convoluted tubule, snakebite, venom

Resumo Inglês:

Background: Porthidium lansbergii hutmanni species occurs at Tropical level (800 meters altitude) in Margarita Island,
Venezuela. It seems to be constrained to this island. Two different species; Porthidium lansbergii rozei and P. lansbergii
lansbergii live in the mountains surrounding the Cordillera de La Costa in mainland Venezuela. The principal damage and the
main complication in fatal cases of Viperidae snakebites in Venezuela is acute renal failure (ARF) secondary to acute tubular
necrosis. Kidney alterations in Porthidium snakebite human victims have concerned inconspicuous considerations. There is
not literature description of Porthidium venom activity on the renal structure. The purpose of this study was to determine how
intraperitoneal Porthidium lansbergii hutmanni venom injection into mice could lead to severe renal injury.
Materials, Methods & Results: Lethal dose fifty (2.5 mg/kg body weight) in mice and polyacrylamide gel electrophoresis
were carried out. Observing renal tissue under the electron microscope 3 h after CvPlh injection, proximal convoluted tubule
showed widening and loss of interdigitations with normal mitochondria. Multiform and pleomorphic mitochondria were seen.
Loss of the cytoarchitecture and empty vacuoles was noticed. After 6 h of CvPlh injection, panoramic view of apical and basal
regions of distal convoluted tubule showed swollen mitochondria cristae; Golgi apparatus swollen elements and different
wideness of interdigitations were seen. High enlarging of the basal membrane, alteration of the interdigitations with the
formation of myelin-like figures were observed. An altered capillary with loss of the wall integrity was visualized. Swollen
mitochondria and swollen rough endoplasmic reticulum were observed. After 24 h of CvPlh injection, in the glomeruli,
rupture of the capillary endothelia, with podocytes of different widened were detected: they were irregulars and of different
sizes. Basal membrane widened in some areas; vacuoles in the endothelial cells were also seen. CvPlh SDS-PAGE profile under
native conditions showed approximately 14 bands distributed from 7.6 to 215.0 kDa.
Discussion: The largest renal lesions observed in the experimental mice were tubular degeneration and necrosis. The alterations
were typically restricted to proximal tubules. Mitochondria modifications were intense. The renal damage caused by CvPlh
appeared to be due to both systemic effects (mainly renal ischemia) and direct tubulotoxic effects of the venom. It was also
found visceral epithelial changes that included podocyte alterations, which could be associated with glomerular dysfunction.
The condition usually causes edema, and nephrotic syndrome and it may progress leading to a renal failure. All renal structures
can be involved. Tubular necrosis is the important pathological counterpart of acute renal failure. As far as we known this is the
first time that after intramuscular administration of P. l .hutmanni venom glomerular and tubular kidney changes have been
observed. It seems likely that mesangiolysis, mitochondria and microvascular damages are a consequence of the high proteolytic
and PLA2 activities of this venom. Studies are being designed to identify the fraction (s) venom responsible (s) for such
ultrastructural changes.