title: Therapeutic potential of peptides with neutralizing ability towards the venom and toxin (CaTx-I) of crotalus adamanteus.
abstract: The CaTx-I (PLA2) toxin of Crotalus adamanteus venom is responsible for most of the symptoms observed during envenomation. Synthetic peptides were designed and screened for venom (0.8 μg/ml) and CaTx-I (0.1 μM) inhibition at varying doses of the peptide (10000- 0.0001 μM) using a Cayman chemical human secretory phospholipase A2 (sPLA2, Type II) assay kit. Further, in vitro neutralization studies were evaluated by a fixed dose of peptide (1 μM) against venom (0.8 μg/ml) and toxin (0.1 μM). Among the linear peptides (PIP-18, cyclic C and PIP59-67) that showed potent neutralizing effects against the venom/toxin of C. adamanteus. PIP-18 [IC50, 1.23 μM] and cyclic C [IC50, 1.27 μM] peptides possessed the strongest inhibitory effect against CaTx-I. A fixed dose of CaTx-I (75 μg/kg) was administered intraperitoneally (i.p.) into mice followed by an i.p. injection of peptides PIP-18 and cyclic C at (6 μg/mouse), venom (150 μg/kg) and toxin CaTx-I alone served as references. Mice treated with PIP-18 and cyclic C showed a very strong neutralizing effect and markedly reduced mortality compared to the control after 24 h. The CA venom and CaTx-I injected mice showed severe toxicity after 24 h. Peptides PIP-18 and cyclic C were non-hemolytic at 100 μM. They produced a significant decrease in lipid peroxidase (LPx) and enhancement of superoxide dismutase (SOD), catalase (CAT) and Glutathione-s-transferase (GST) levels indicating their antioxidant property against venom-induced changes in mice. This study confirmed the potent snake venom neutralizing properties of peptides.
authors.affiliation: Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597. micramar@nus.edu.sg
authors.forename: Ramar Perumal
authors.initials: RP
authors.lastname: Samy
authors.forename: Maung Maung
authors.initials: MM
authors.lastname: Thwin
authors.forename: Bradley G
authors.initials: BG
authors.lastname: Stiles
authors.forename: Ho
authors.initials: H
authors.lastname: Bow
authors.forename: Vincent T K
authors.initials: VT
authors.lastname: Chow
authors.forename: Ponnampalam
authors.initials: P
authors.lastname: Gopalakrishnakone
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis / Q000494:pharmacology; D000997:Antivenins / Q000737:chemistry / Q000494:pharmacology; D002374:Catalase / Q000032:analysis / Q000378:metabolism; D003435:Crotalid Venoms / Q000037:antagonists & inhibitors* / Q000737:chemistry; D017839:Crotalus / Q000502:physiology*; D003439:Crotoxin / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000302:isolation & purification; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D005982:Glutathione Transferase / Q000032:analysis / Q000378:metabolism; D020128:Inhibitory Concentration 50; D007274:Injections, Intraperitoneal; D013058:Mass Spectrometry; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D009195:Peroxidase / Q000032:analysis / Q000378:metabolism; D064801:Phospholipase A2 Inhibitors; D054467:Phospholipases A2 / Q000737:chemistry / Q000302:isolation & purification; D012909:Snake Bites / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D013482:Superoxide Dismutase / Q000032:analysis / Q000378:metabolism; D015996:Survival Rate
chemical_list: D000975:Antioxidants; D000997:Antivenins; D003435:Crotalid Venoms; D010455:Peptides; D064801:Phospholipase A2 Inhibitors; D003439:Crotoxin; D002374:Catalase; D009195:Peroxidase; D013482:Superoxide Dismutase; D005982:Glutathione Transferase; D054467:Phospholipases A2