Contribution of metalloproteases, serine proteases and phospholipases A2 to the inflammatory reaction induced by Bothrops jararaca crude venom in mice.
Various toxins isolated from Bothrops snake venoms induce inflammatory reactions and have been claimed to contribute to the severity of local symptoms present in this envenomation. Notwithstanding, the relative participation of serine proteases, metalloproteases and phospholipases A(2) in the inflammatory reaction produced by crude Bothrops venoms is poorly understood. Herein, crude Bothrops jararaca venom was treated with phenylmethanesulfonyl fluoride (PMSF), 1,10-phenanthroline (oPhe), or p-bromophenacyl-bromide (p-BPB) to inhibit those classes of enzymes, respectively, and inflammatory parameters were evaluated and compared to those induced by the control crude venom. The intensity of edema and hyperalgesia/allodynia was remarkably reduced in animals administered with oPhe-treated venom. Leukocyte-endothelium interactions (LEI), such as adhesion and migration of leukocytes, were also modified at 2h and 24h. Edema and LEI parameters induced by p-BPB-treated venom were similar to those observed with the control venom, but hyperalgesia/allodynia was significantly lower. Inflammatory parameters induced by PMSF-treated venom were similar to those induced by the crude venom, except for a mild reduction in edema intensity. Our results indicate that metalloproteases have a pivotal role in the inflammatory reactions induced by B. jararaca venom, and phospholipases A(2) and serine proteases have a minor role.
Zychar
Bianca Cestari
BC
Laboratório de Fisiopatologia, Instituto Butantan, Av. Vital Brazil, 1500, 05503-900 São Paulo, SP, Brazil.
Dale
Camila Squazoni
CS
Demarchi
Denise Soares
DS
Gonçalves
Luis Roberto C
LR
D000818:Animals; D017837:Bothrops; D002465:Cell Movement / Q000187:drug effects; D004487:Edema / Q000139:chemically induced / Q000473:pathology; D042783:Endothelial Cells / Q000187:drug effects; D006930:Hyperalgesia / Q000139:chemically induced / Q000523:psychology; D007249:Inflammation / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D045726:Metalloproteases / Q000633:toxicity*; D051379:Mice; D009504:Neutrophils / Q000187:drug effects; D010147:Pain Measurement / Q000187:drug effects; D064801:Phospholipase A2 Inhibitors; D054467:Phospholipases A2 / Q000633:toxicity*; D010812:Physical Stimulation; D011480:Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology; D057057:Serine Proteases / Q000633:toxicity*; D015842:Serine Proteinase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D014757:Viper Venoms / Q000201:enzymology* / Q000633:toxicity*
D064801:Phospholipase A2 Inhibitors; D011480:Protease Inhibitors; D015842:Serine Proteinase Inhibitors; D014757:Viper Venoms; D054467:Phospholipases A2; D045726:Metalloproteases; D057057:Serine Proteases