Objective: Peripheral neurotoxic effects (PNE) after European viper envenomation have been reported both in Italy and South-Eastern France. PNE involve mostly cranial nerves and can be related to the presynaptic toxicity of phospholipases-A2 (PLA2) that causes neuromuscular paralysis. Currently PLA2 in Italian viper has never been demonstrated. The aims of this study are to identify PNE observed in patients referred to Pavia Poison Centre after viper bite, and describe presence and activity of PLA2 in Italian viper venom. Methods: Clinical data: Patients with PNE after viper bite observed between 2001-2008 were reviewed and valuated for local, neurological and non-neurological manifestations. Experimental data: Venom milked from 3 adults of Italian Vipera aspis was analyzed through a polyacrylamide gel electrophoresis. Venom activity was tested with mouse phrenic nerve-hemidiaphragm and stimulated by supramaximal stimuli of 3-6 V amplitude and 0.1 millisecond pulse with a frequency of 0.1Hz; isometric muscle contraction was monitored and a curve of paralysis was registered. Immortalized motor neuron cell line was incubated with venom. Results: Clinical data: Eighteen patients were observed (3-75 years). PNE included bilateral ptosis (16/18 patients), diplopia (6/18), dysphagia (3/18). Patients showed mild (6/18), moderate (10/18) or massive limb oedema (2/18). Systemic non-neurotoxic effects were vomiting (12/18), abdominal pain (6/18) and diarrhea (5/18). Five patients showed PNE as unique systemic manifestation. PNE were observed 3-30 hours after bite; systemic non-neurotoxic effects occurred earlier. Experimental data: SDS-gel electrophoresis of venom showed proteins with molecular mass resembling PLA2. Venom added to mouse hemidiaphragm caused a biphasic curve of paralysis without impairment of muscle contraction. Incubation of neuronal cells with venom induced a defined swelling of synaptic sites with formation of bulges similar to other snake neurotoxins with PLA2 activity. Discussion: PNE observed seems potentially connected with the action of PLA2. PNE can occur with delayed onset, even in patients presenting only local effects. PLA2 was detected in all venom samples analyzed. Nevertheless patients without signs of neurotoxicity are reported, and this could be related to the amount of venom injected, the concentration of PLA2 and a possible individual susceptibility.

Clinical and experimental evidencies of Italian viper venom neurotoxicity

GENTILLI, AUGUSTO SERGIO;SACCHI, ROBERTO;BERNINI, FRANCO;
2010-01-01

Abstract

Objective: Peripheral neurotoxic effects (PNE) after European viper envenomation have been reported both in Italy and South-Eastern France. PNE involve mostly cranial nerves and can be related to the presynaptic toxicity of phospholipases-A2 (PLA2) that causes neuromuscular paralysis. Currently PLA2 in Italian viper has never been demonstrated. The aims of this study are to identify PNE observed in patients referred to Pavia Poison Centre after viper bite, and describe presence and activity of PLA2 in Italian viper venom. Methods: Clinical data: Patients with PNE after viper bite observed between 2001-2008 were reviewed and valuated for local, neurological and non-neurological manifestations. Experimental data: Venom milked from 3 adults of Italian Vipera aspis was analyzed through a polyacrylamide gel electrophoresis. Venom activity was tested with mouse phrenic nerve-hemidiaphragm and stimulated by supramaximal stimuli of 3-6 V amplitude and 0.1 millisecond pulse with a frequency of 0.1Hz; isometric muscle contraction was monitored and a curve of paralysis was registered. Immortalized motor neuron cell line was incubated with venom. Results: Clinical data: Eighteen patients were observed (3-75 years). PNE included bilateral ptosis (16/18 patients), diplopia (6/18), dysphagia (3/18). Patients showed mild (6/18), moderate (10/18) or massive limb oedema (2/18). Systemic non-neurotoxic effects were vomiting (12/18), abdominal pain (6/18) and diarrhea (5/18). Five patients showed PNE as unique systemic manifestation. PNE were observed 3-30 hours after bite; systemic non-neurotoxic effects occurred earlier. Experimental data: SDS-gel electrophoresis of venom showed proteins with molecular mass resembling PLA2. Venom added to mouse hemidiaphragm caused a biphasic curve of paralysis without impairment of muscle contraction. Incubation of neuronal cells with venom induced a defined swelling of synaptic sites with formation of bulges similar to other snake neurotoxins with PLA2 activity. Discussion: PNE observed seems potentially connected with the action of PLA2. PNE can occur with delayed onset, even in patients presenting only local effects. PLA2 was detected in all venom samples analyzed. Nevertheless patients without signs of neurotoxicity are reported, and this could be related to the amount of venom injected, the concentration of PLA2 and a possible individual susceptibility.
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11571/208325
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact