Contribution of metalloproteases, serine proteases and phospholipases A2 to the inflammatory reaction induced by Bothrops jararaca crude venom in mice

Abstract

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.

Jararhagin-induced mechanical hyperalgesia depends on TNF-α, IL-1β and NFκB in mice

“…In agreement with the role of cytokines in pain, inhibiting NFkB activation also reduces pain (Possebon et al, 2014;Tegeder et al, 2004). Pain is an important clinical component of snakebites (Bonavita et al, 2006;Rocha et al, 2000;Zychar et al, 2010) and the mechanisms underlying B. jararaca snake venom and jararhagininduced pain are incompletely understood. Despite jararhagin induction of TNF-a and IL-1b production in other systems (Clissa et al, 2006;Laing et al, 2003), and the hyperalgesic role of TNF-a and IL-1b, and NFkB (Verri et al, 2006), the contribution of cytokines and NFkB to jararhagin-induced mechanical hyperalgesia remains to be determined.…”

Lonomia obliqua venomous secretion induces human platelet adhesion and aggregation

“…These inhibitors have been used in several previous works to identify and characterize the different classes of enzymes present in L. obliqua and some snake venoms [18,21,22,25]. Here, we used a similar approach in order to verify the possible contribution of each of these enzymes to the venom platelet pro-aggregating activity.…”

Inflammatory mediators involved in the paw edema and hyperalgesia induced by Batroxase, a metalloproteinase isolated from Bothrops atrox snake venom

“…BaP1, a metalloproteinase from B. asper venom, also induced hyperalgesia, but in contrast to Batroxase, it showed a maximum response 2 h after injection [26]. According to Zychar et al [79], metalloproteinases present in the venom of B. jararaca are the main responsible for the hyperalgesia induced by this venom.…”