Accidents caused by the venomous fish Thalassophryne nattereri are characterized by
edema, intense
pain and
necrosis at the site of the
sting. This study assessed the nociceptive and edematogenic activities of T. nattereri
venom after injection into the mouse hindpaw and determination of the paw licking duration and weight. Subplantar
injections of the
venom (0.1-6 microg) induced a dose-related increase of the paw licking time and paw swelling with maximal values at 3 microg (209.5 +/- 57.5 s and 135.0 +/- 6.8 mg, respectively). Pretreatment of mice with either
indomethacin (10 mg/kg, i.p.), a
cyclooxygenase inhibitor,
dexamethasone (1 mg/kg, s.c.), a
steroid anti-inflammatory agent,
cyproheptadine (1 mg/kg, i.p.), antagonist of
serotonin receptors or
L-NAME (100 mg/kg, s.c.), inhibitor of
nitric oxide syntase, did not affect the
venom-induced nociceptive and edematogenic responses. Injection of the
opioid analgesic fentanyl (0.1 mg/kg, s.c.) reduced the paw licking time induced by 1 microg
venom by 84% of control, without affecting the paw swelling. Both nociceptive and edematogenic responses were reduced
after treatment with a specific
tissue kallikrein inhibitor (TKI, 100 mg/kg, i.p.) by 78% and 24% from control values, respectively. Administration of a specific
plasma kallikrein inhibitor (
PKSI(527,) 100 mg/kg, s.c.) did not affect the
venom-induced nociceptive response, but it decreased the paw
edema by 15% from control. After injection of the
angiotensin-converting enzyme inhibitor captopril (100 mg/kg, i.p.) the
venom-induced nociceptive end edematogenic responses were increased by two-fold. The role of
kallikreins possibly present in the
venom was further assessed by hydrolysis of human
kininogen and
kininogen-derived synthetic
peptides, showing the release of
kallidin (
Lys-bradykinin). The hydrolysis was inhibited by
metal chelating agents but not by serino-, aspartyl- or cysteino-
proteinase inhibitors. The data suggest that a
protease with
tissue-kallikrein-like activity plays a major role in nociception and
edema induced by T. nattereri
venom and this should be considered to achieve efficient treatments for human accidents with this
venom.