Histologic and functional renal alterations caused by Bothrops moojeni snake venom in rats.

Abstract

Abstract. Acute renal failure (ARF) is the main cause of death following snake bites by Bothrops species. In this study, we investigated the morphologic and functional renal disturbances caused by Bothrops moojeni venom in rats. Renal function was assessed based on creatinine and lithium clearances and on histologic examination of renal tissue 5 hr after the intravenous administration of 0.2 mg of venom/kg and 5 hr, 16 hr, and 48 hr after 0.4 mg of venom/ kg. A venom dose of 0.4 mg/kg produced renal tubule disturbances, including acute impairment of proximal and post-proximal tubule sodium handling associated with acute tubule necrosis. The glomerular filtration rate (GFR) decreased significantly and was accompanied by severe morphologic disturbances in the renal glomeruli. These functional and morphologic findings were observed in the absence of any change in mean arterial blood pressure. The decrease in GFR was not related to the presence of fibrin deposits in the glomerular capillary loops. These results suggest an early nephrotoxic action of B. moojeni venom involving significant morphologic and functional changes similar to those observed in snakebite-induced ARF in humans. Envenomation following snakebite is a health problem in tropical regions of the world. The genus Bothrops contains many species distributed from Mexico to Argentina. 1 Of the 20,000 snakebite accidents per year in Brazil, about 90% are attributed to the genus Bothrops. 2 Bothrops moojeni is the most common cause of snakebite in central Brazil (Cardoso JLC, unpublished data). In common with other Bothrops venoms, 3-7 B. moojeni venom contains blood-clotting, hemorrhagic, phospholipase A 2 , and proteolytic activities. 8 Envenomation by Bothrops species leads to local and systemic effects that develop simultaneously. The local lesions include edema, pain, erythema, ecchymosis, bullae, cyanosis, necrosis, and cellulitis. The most serious systemic change and primary cause of death is acute renal failure (ARF) secondary to acute tubular necrosis and, occasionally, glomerulonephritis. 3,4,7,[9][10][11][12][13][14] Thus, elucidation of the mechanisms involved in this nephrotoxicity is important. Experimental models used to investigate the pathogenesis of renal lesions caused by bothropic venoms have shown hemodynamic changes and hemolysis prior to renal ischemia. 4,6,15 Ischemia caused by massive fibrin deposition in the glomerular capillaries as well as intravascular hemolysis appear to have a crucial role in the physiopathology of renal failure. 16 However a direct nephrotoxic action of the venom cannot be excluded.In this work, we studied the pathogenesis of the alterations in renal function and morphology in rats after a single intravenous injection of B. moojeni venom. Experimental protocol. One group of rats was injected with venom (V 1 ) and another, which served as the control group, received 0.15 M NaCl solution (S 1 ). The renal function of both groups was evaluated 5 hr (V, n ϭ 7; S, n ϭ 5), 16 hr (V, n ϭ 6; S, n ϭ 4), and 48 hr (V,...

Bothrops moojeni snake venom-induced renal glomeruli changes in rat.

“…9 Significant proteinuria occurred 5 hours, 16 hours, and 48 hours after venom. However, the level of proteinuria had recovered considerably after 48 hours, indicating that the process was reversible.…”

“…8 We observed a significant decrease in the glomerular filtration rate, an increase in the fractional urinary Na + and K + excretion, and significant histological changes in the tubular and glomerular structure after intravenous injection of Bothrops moojeni venom. 9 The alterations observed by light microscopy include glomerulonephritis characterized by hypercellularity, glomeruli lobulation with retraction of the capillary tuft, and condensed mesangial matrix-forming nodular lesions. The mean arterial pressure remained unchanged.…”

Aspectos clinicopatológicos e laboratoriais do envenenamento experimental por Bothrops moojeni e Bothropoides neuwiedi em ovinos

“…No caso do envenenamento por serpentes, estudos em ratos com ação do veneno de Bothrops moojeni concluíram que há efeito nefrotóxico direto em células tubulares renais (Boer-Lima et al 1999).…”

Fatal bothropic snakebite in a horse: a case report

“…The increase in urea and creatinine levels may be explained by the acute renal failure that may occur due to several factors, such as disseminated intravascular coagulation, hypotension, direct nephrotoxic action of the venom, and hemolysis (11,12). Tachycardia and tachypnea may be due to the stress and pain (3).…”