Scorpion venoms are known to cause different inflammatory disorders through complex mechanisms in various tissues. In the study here, the involvement of
phospholipase A2 (PLA2) and
cyclo-oxygenase (COX)-derived metabolites in hepatic and renal
inflammation responses were examined. Mice were envenomed with Androctonus australis hector
scorpion venom in the absence or presence of inhibitors that can interfere with
lipid inflammatory mediator synthesis, i.e.,
dexamethasone (PLA2 inhibitor),
indomethacin (non-selective COX-1/
COX-2 inhibitor), or
celecoxib (selective
COX-2 inhibitor). The inflammatory response was assessed by evaluating vascular permeability changes, inflammatory cell infiltration, oxidative/nitrosative stress marker levels, and by histologic and functional analyses of the liver and kidney. Results revealed that the
venom alone induced an inflammatory response in this tissues marked by increased microvascular permeability and inflammatory cell infiltration, increases in levels of
nitric oxide and lipid peroxidation, and decreases in
antioxidant defense. Moreover, significant alterations in the histological architecture of these organs were associated with increased serum levels of some metabolic
enzymes, as well as
urea and
uric acid. Pre-treatment of mice with
dexamethasone led to significant decreases of the inflammatory disorders in the hepatic parenchyma;
celecoxib pre-treatment seemed to be more effective against renal
inflammation.
Indomethacin pre-treatment only slightly reduced the inflammatory disorders in the tissues. These results suggest that the induced
inflammation response in liver was mediated mainly by PLA2 activation, while the renal inflammatory process was mediated by
prostaglandin formation by COX-2. These findings provide additional insight toward the understanding of activated pathways and related mechanisms involved in
scorpion envenoming syndrome.