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American Journal of Pathology, Vol 122, 240-251, Copyright © 1986 by American Society for Investigative Pathology

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Glomerular injury in mice induced by Agkistrodon venom

N Sakurai, K Sugimoto, H Sugihara, H Shirasawa, H Muro, M Kaneko, T Nikai and K Shibata

Glomerular injury was produced in mice after a single LD50 intravenous dose of purified 100-pace snake venom (Agkistrodon acutus). Characteristic features in glomeruli where the venom was demonstrated immunohistochemically included cystic lesions of the capillary tufts, thrombosis, subsequent proliferative and sclerotic changes, and crescent formation. Venom was recognized immunohistochemically in the glomerular endothelium, visceral basement membrane, mesangium, epithelium, and Bowman's capsule. Venom transfer across the basement membrane or into cells required less than 2 hours. Within this period mesangiolysis occurred due to the protease activity of the venom. Cystic lesions with fibrin thrombi then developed, which were replaced by proliferative and sclerotic changes after 3 days. Crescent formation began within 48 hours and was completed within a few days. Microangiography revealed hemodynamic changes in the intrarenal vasculature after venom treatment. Immune complex deposition was not found in any tissue. The study demonstrates the moderately constant potency (LD50) of Agkistron acutus venom, and documents it as a useful tool for quantitative studies of renal lesions.