Efeito renal do veneno da Bothrops erythomelas e bloqueio induzido pelo fator antibotrópico do Dedelphis marsupialis

Abstract

Some animals present natural resistance to the effects of snake venoms that can be explained by the presence of neutralizing factors in their blood serum. The resistance of South American Didelphis marsupialis, against crotalid venoms, especially of the genus Bothrops, of utmost medical importance in Brazil, has been object of investigation in the last few years. Bothrops erythromelas, known as “jararaca-da-seca” or “jararaca-malha-de-cascavel” is responsible for a great deal of snakebites in Northeastern Brazil. The venom of this snake induces acute renal failure (Wen et al., 1989). In this work, we examined the action of the antibothropic factor isolated from Didelphis marsupialis on the renal effects of B. erythromelas venom in the absence of systemic interactions. Isolated kidneys from Wistar rats, weighing 260 to 300g, were perfused with Krebs-Henseleit solution containing 6g% of bovine serum albumin, Bothrops erythromelas venom (10mg/mL), antibothropic factor from Didelphis marsupialis (10mg/mL), antibothropic factor from Didelphis marsupialis (10mg/mL) incubated with Bothrops erythromelas venom (10mg/mL) and antibothropic factor from Didelphis marsupialis (30mg/mL) incubated with Bothrops erythromelas venom (10mg/mL). The parameters studied included perfusion pressure (PP), renal vascular resistance (RVR), glomerular filtration rate (GFR), urinary flow (UF), percent sodium, potassium and chloride tubular transport (%TNa+, %TK+ and %TCl-), and osmotic clearance (Cosm). The control group perfused with albumin was functionally stable for over 120 min. The administration of antibothropic factor from Didephis marsupialis (10µg/mL) did not modify the functional kidney parameters when compared with control group. The infusion of B. erythromelas venom (10µg/mL) caused a significant decrease (p< 0,05*) in perfusion pressure and renal vascular resistance at 60, 90 and 120 min. with maximum effect at 90 min. (PP→ ct90 = 108.70 ± 5.1 mmHg vs vBE90 = 65.20 ± 5.6* mmHg) and (RVR→ ct90 = 5.76 ± 0.65 mmHg/mL.g-1.min-1. vs vBE90 = 3.10 ± 0.45* mmHg/mL.g-1.min-1). The glomerular filtration rate decreased at 60 min. and increased at 90 and 120 min (ct120 = 0.72 ± 0.10 mL.g-1.min-1. vs vBE120 = 1.24 ± 0.26* mL.g-1.min-1). After administration of the venom, the urinary flow increased at 90 and 120 min when compared with control group (ct120 = 0.14 ± 0.07 mL.g-1.min-1. vs vBE120 = 0.47 ± 0.08* mL.g-1.min-1). Sodium transport percent decreased at 90 and 120 min. (ct90 = 79.18 ± 0.88% vs vBE90 = 58.35 ± 4.86* %). Potassium transport percent decreased at 90 and 120 min. (ct90 = 67.20 ± 4.04% vs vBE90 = 57.32 ± 5.28* %). Chloride transport percent decreased at 60, 90 and 120 min. (ct90 = 77.32 ± 2.22% vs vBE90 = 55.97 ± 5.52* %). The osmotic clearance increased at 90 and 120 min. (ct120 = 0.13 ± 0.01 mL. g-1.min-1 vs vBE120 = 0.42 ± 0.07* mL.g-1.min-1). The antibothropic factor from Didelphis marsupialis (10µg/mL) incubated with B. erythromelas venom (10µg/mL) blocked only the effects promoted by venom in the perfusion pressure and in the renal vascular resistance, whereas the highest concentration of the antibothropic factor from Didelphis marsupialis (30µg/mL) reversed the effects on renal vascular resistance, urinary flow, glomerular filtration rate, percent sodium potassium and chloride tubular transport (%TNa+, %TK+ and %TCl-), and osmotic clearance (Cosm). In conclusion, B. erythromelas venom altered all the renal functional parameters evaluated and the antibothropic factor from D.marsupialis was able to inhibit the effects induced by the venom in rat isolated kidney.