Effects of Snake-Derived Phospholipase A2 Inhibitors on Acute Pancreatitis: In vitro and in vivo Characterization.

Abstract

OBJECTIVE:

We aimed to investigate the effects of snake-derived phospholipase A2 inhibitor (PLA2) from Sinonatrix percarinata and Bungarus multicinctus on acute pancreatitis in vivo and in vitro and assess the mechanisms.

METHODS:

The levels of platelet-activating factor (PAF) and tumor necrosis factor (TNF)-α were detected by ELISA, and the characteristics of autophagy were detected by transmission electron microscopy and Western blotting (LC3, p62, and ATG5).

RESULTS:

In vitro experiments showed that PLA2 treatment caused obvious formation of autophagic bodies. By contrast, Sinonatrix and Bungarus peptides reduced the number of autophagic bodies. The concentrations of PAF and TNF-α, and the expressions of p62, autophagy-related 5 (ATG5), and microtubule-associated protein 1A/1B-light chain 3 (LC3)II/LC3I in the PLA2-treated group were significantly higher than in the control group (P<0.05). The concentrations of PAF and TNF-α, and the expressions of p62, ATG5, and LC3II/LC3I in the Sinonatrix or Bungarus peptide treatment groups were significantly lower than in the PLA2-treated cells (P<0.05). In the pancreatic tissue, autophagic bodies were observed in the model group; autophagic bodies were remarkably reduced in Sinonatrix or Bungarus peptide-treated groups compared with the model group. In vivo experiments also showed that the levels of PAF and TNF-α, and the expressions of p62, ATG5, and LC3II/LC3I were significantly higher in the model group than in the control group (P<0.05). The levels of PAF and TNF-α in the model group, and the expressions of p62, ATG5, and LC3II/LC3I in Sinonatrix or Bungarus peptide-treated groups were significantly lower than in the model group (P<0.05).

CONCLUSION:

Sinonatrix or Bungarus peptide could ameliorate the features of acute pancreatitis, likely through regulating autophagy.

• Authors: Yanping Wu, Gen-You Liao, Hua-Jing Ke, Pi Liu
• Journal: Drug design, development and therapy (Drug Des Devel Ther) Vol. 14 Pg. 4765-4774 ( 2020) ISSN: 1177-8881 [Electronic] New Zealand
• PMID: 33192052 (Publication Type: Journal Article)
• Copyright: © 2020 Wu et al.

Chemical References

• Peptides
• Phospholipase A2 Inhibitors
• Phospholipases A2

Topics

• Animals
• Cells, Cultured
• Disease Models, Animal
• Injections, Intraperitoneal
• Mice
• Pancreatitis (drug therapy, metabolism)
• Peptides (administration & dosage, chemistry, pharmacology)
• Phospholipase A2 Inhibitors (administration & dosage, chemistry, pharmacology)
• Phospholipases A2 (metabolism)
• Rats
• Snakes