Bothrops venom induces direct renal tubular injury: role for lipid peroxidation and prevention by antivenom.
Acute renal failure (ARF) is one of the most serious complications of Bothrops snakebites. Pathogenesis of ARF in snakebite envenomation may involve hemodynamic disturbances, immunologic reactions and direct nephrotoxicity. This study aimed at evaluating Bothrops jararaca venom direct toxicity on isolated rat renal proximal tubules (PT). PT was kept oxygenated and subjected to hypoxia (H, 15 min) and reoxygenation (R, 45 min). Bothropic antivenom effects, role of extracellular calcium and peroxide production were also evaluated. Cell injury was determined by LDH release (%) and peroxide production determined by xylenol-orange method. B. jararaca venom caused tubular injury (LDH 31.6 vs. 17.2%, P <0.05), which was prevented by simultaneous or delayed antivenom administration, but not with low extracellular calcium medium. Venom increased tubules peroxide production: 2.21 vs. 1.27 microM/mg protein (P <0.05) which was also prevented by antivenom administration. Venom toxic concentration did not enhance H/R injury. In contrast, non-toxic venom concentration afforded protection (LDH 41.3 vs. 51.5%, P <0.05). In conclusion, B. jararaca venom caused direct injury to normoxic renal tubules, but not to hypoxic/reoxygenated tubules. Tubular toxicity is independent of extracellular calcium and mediated in part by lipid peroxidation. Venom induced tubular injury was prevented by simultaneous or delayed antivenom administration.
Nephrology-LIM 12, School of Medicine, University of São Paulo, Av. Dr. Arnaldo 455-3 degrees A-S. 3310, São Paulo 01246-903, Brazil.
Isac
I
de Castro
Emmanuel A
EA
Burdmann
Antonio Carlos
AC
Seguro
Luis
L
Yu
D000704:Analysis of Variance; D000818:Animals; D000997:Antivenins / Q000627:therapeutic use*; D017837:Bothrops; D002118:Calcium / Q000378:metabolism; D003435:Crotalid Venoms / Q000633:toxicity*; D004195:Disease Models, Animal; D006861:Hydrogen Peroxide / Q000378:metabolism; D007683:Kidney Tubular Necrosis, Acute / Q000139:chemically induced / Q000188:drug therapy* / Q000517:prevention & control; D007684:Kidney Tubules / Q000473:pathology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000502:physiology; D008297:Male; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D000997:Antivenins; D003435:Crotalid Venoms; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; D010100:Oxygen; D002118:Calcium