Analysis of nociceptive effects of neurotoxic phospholipase A2 from Vipera nikolskii venom in mice

Abstract

Phospholipases A2 are represented in snake venoms by several types and possess diverse biological activities including neurotoxicity. Previously, we isolated and characterized two neurotoxic phospholipases A2 (HDP-1 and HDP-2) from the venom of Nikolski's viper (Vipera nikolskii), which were heterodimers composed of two non-covalently bound subunits. Each heterodimer consisted of an enzymatically active basic subunit and an inactive acidic subunit. In this work, we studied the in vivo biological activity of HDP-2 in mice. The acute toxicity (LD50 = 0.38 μg/gm) and maximal tolerated dose (0.1 μg/gm) were determined. In the hot plate test, HDP-2 at the maximal tolerated dose, reliably prolonged the time of the mouse staying on the plate. However, taking into account the neurotoxicity of HDP-2, we believe that this effect may be explained by a general intoxication rather than specific decrease of pain sensitivity. In this respect HDP-2 differs from other heterodimeric phospholipases A2 like crotoxin, which possess analgesic activity. This difference can be explained by the dissimilarity in the structure of the acidic subunits, suggesting an important role of this subunit in analgesic activity.

Keywords: Phospholipase A2; nociception; snake; toxicity; venom; α-neurotoxin.

Figure 1.

Amino acid sequences of crotoxin and HDP-2. HDP-I and HDP-2P are acidic and basic subunits of HDP-2, respectively (Ramazanova et al, 2008). Crotoxin chain B - basic subunit of crotoxin (Bouchier et al, 1991). Identical amino acid residues are shaded in grey. Crossed residues indicate fragments removed from the precursor during processing.