title: Inhibitory effects of bile acids on enzymatic and pharmacological activities of a snake venom phospholipase A(2) from group IIA.
abstract: Bile acids, such as cholic acid (CA) and ursodeoxycholic acid (UDCA) have shown to decrease or increase the enzymatic activity of group IB pancreatic PLA(2), depending on the concentration used. Studies suggest that the inhibition of hydrolysis rate of the substrate is due to formation in aqueous phase of a complex between bile acid and PLA(2), which is catalytically inert. For this reason, we tested the inhibition of the enzymatic activity of group IIA snake venom PLA(2) by bile acids, using an aqueous phase model. In addition, we measured the ability of bile acids to inhibit the toxic effects caused by the mentioned toxin. UDCA and CA inhibited the enzymatic activity of the PLA(2) in a competitive mode. Moreover, these compounds inhibited myotoxic, cytotoxic and edema-forming activities induced by the toxin, but UDCA was more efficient than CA. It was demonstrated that bile acids interact directly with this protein by causing slight changes in the intrinsic fluorescence spectra. Preliminary molecular docking studies suggest that bile acids interact with amino acids at the active site of the PLA(2) through different interactions, CA showed hydrogen bonds with His48, whereas, UDCA displayed with Asp49. Results obtained herein may turn UDCA and CA into promising models for the development of new molecules with anti-inflammatory and anti-snake venom PLA(2) properties.
authors.affiliation: Programa de Ofidismo/Escorpionismo, Universidad de Antioquia, A.A. 1226, Medellín, Colombia. andrespj20@yahoo.es
authors.forename: Jaime Andrés
authors.initials: JA
authors.lastname: Pereañez
authors.forename: Vitelbina
authors.initials: V
authors.lastname: Núñez
authors.forename: Arley Camilo
authors.initials: AC
authors.lastname: Patiño
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000302:isolation & purification / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D019826:Cholic Acid / Q000494:pharmacology*; D003435:Crotalid Venoms / Q000009:adverse effects / Q000037:antagonists & inhibitors* / Q000302:isolation & purification / Q000378:metabolism; D017839:Crotalus / Q000378:metabolism*; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D051379:Mice; D008958:Models, Molecular; D064801:Phospholipase A2 Inhibitors; D054467:Phospholipases A2 / Q000009:adverse effects / Q000302:isolation & purification / Q000378:metabolism; D011485:Protein Binding; D014580:Ursodeoxycholic Acid / Q000494:pharmacology*
chemical_list: D000925:Anticoagulants; D003435:Crotalid Venoms; D064801:Phospholipase A2 Inhibitors; D014580:Ursodeoxycholic Acid; D054467:Phospholipases A2; D019826:Cholic Acid