Pharmacological activities of a toxic phospholipase a isolated from the venom of the snake Bothrops Asper

Abstract

1. A toxic phospholipase A was isolated from the venom of Bothrops asper. It induced skeletal muscle damage, anticoagulant effects and edema in the foot pad. 2. The toxin had an intravenous ld 50 of 95 μg/16–18 g mouse body wt and an intraventricular ld 50, of 0.42 μg/16–18 g mouse body wt. 3. Upon intramuscular and intravenous injections, the toxin induced a prominent increase in serum creatine kinase (CK) levels; only the CK-MM isozyme increased markedly. 4. The toxin induced CK and creatine release from skeletal muscle incubated in vitro. The rate of efflux of creatine was higher than that of CK, although both markers were partially released as early as 15 min after incubation. 5. The toxin also induced elevation of serum levels of lactic dehydrogenase isozymes. However, histological examination of skeletal muscle, kidneys, heart and lungs revealed cell damage only in skeletal muscle. 6. The toxin was not cytotoxic to erythrocytes, lymphocytes or macrophages. In addition, it did not induce a mitogenic response on lymphocytes. 7. In the absence of albumin in the medium, there was no significant difference between myotoxic activities in Ca 2+-free and Ca 2+-containing bathing solutions. However, when albumin was added, there was a significantly higher myotoxic effect in the presence of Ca 2+. Thus, although phospholipolytic activity of the toxin plays a role in muscle damage when albumin is present, the toxin induces muscle damage even when phospholipase A activity is inhibited.