In
snake venoms, non-covalent
protein-
protein interaction leads to
protein complexes with synergistic and, at times, distinct pharmacological activities. Here we describe a new
protein complex containing phospholipaseA(2) (PLA(2)),
protease, and a
trypsin inhibitor. It is isolated from the
venom of Daboia russelii by gel permeation chromatography, on a
Sephadex G-75 column. This 44.6 kDa complex exhibits only
phospholipase A(2) activity. In the presence of 8M
urea it is well resolved into
protease (29.1 kDa), PLA(2) (13 kDa), and
trypsin inhibitor (6.5 kDa) peaks. The complex showed an LD(50) of 5.06 mg/kg
body weight in mice. It inhibited the frequency of spontaneous release of
neurotransmitter in hippocampal neurons. It also caused peritoneal
bleeding, and
edema in the mouse foot pads. Interestingly, the complex caused degeneration of both the germ cells and the mouse Leydig cells of mouse testis. A significant reduction in both the diameter of the seminiferous tubules and height of the seminiferous epithelia were observed following
intraperitoneal injection of the sub-lethal dose (3 mg/kg
body weight). This effect of the toxin is supported by the increase in the activities of
acid and alkaline
phosphatases and the
nitric oxide content in the testes, and a decrease in the
ATPase activity. Because of its potent organ atrophic effects on the reproductive organs, the toxin is named "Reprotoxin". This is the first report demonstrating toxicity to the reproductive system by a toxin isolated from
snake venom.