Stingray (Potamotrygon rex) maturity is associated with inflammatory capacity of the venom.

Several studies have been carried out with venom from sting and mucus of stingrays of marine or fluvial environments to compare the toxicity of their venom. However, studies demonstrating the existence of the influence of both sex and the maturation stage of stingrays on the variability of the toxic effects of venom are still scarce. Here, we investigated whether the sex and/or the stage maturation of the Potamotrygon rex stingray influence the toxic capacity of the venom to develop acute inflammation in mice. We carried out the main toxic activities in mice using venom from female or male of young and adult stingrays. Our results described here show that the nociception is mainly induced by venom from young female stingrays. In contrast, we observed the action of venom from both sex of adult stingrays in the induction of exudative phase of inflammatory process, including vascular leakage and neutrophil infiltration. Our data illustrate that the composition of the venom of P. rex is influenced by the stage of maturity of the stingray, modulating the production of peptides and proteins capable of acting on leukocytes-endothelial interactions and favoring neutrophil infiltration to the damage tissue.

Stingray (Potamotrygon rex) maturity is associated with inflammatory capacity of the venom

Several studies have been carried out with venom from sting and mucus of stingrays of marine or fluvial environments to compare the toxicity of their venom. However, studies demonstrating the existence of the influence of both sex and the maturation stage of stingrays on the variability of the toxic effects of venom are still scarce. Here, we investigated whether the sex and/or the stage maturation of the Potamotrygon rex stingray influence the toxic capacity of the venom to develop acute inflammation in mice. We carried out the main toxic activities in mice using venom from female or male of young and adult stingrays. Our results described here show that the nociception is mainly induced by venom from young female stingrays. In contrast, we observed the action of venom from both sex of adult stingrays in the induction of exudative phase of inflammatory process, including vascular leakage and neutrophil infiltration. Our data illustrate that the composition of the venom of P. rex is influenced by the stage of maturity of the stingray, modulating the production of peptides and proteins capable of acting on leukocytes-endothelial interactions and favoring neutrophil infiltration to the damage tissue.

Potamotrygon motoro stingray venom induces both neurogenic and inflammatory pain behavior in rodents.

Freshwater stingray accidents cause an immediate, intense, and unrelieved pain which is followed by edema, erythema and necrosis formation. Treatment for stingray envenomation is based on administration of analgesic, antipyretic and anti-inflammatory drugs. Concerning pain control, it is prescribed to immerse punctured limb on hot water to alleviate pain. There are no studies demonstrating specific targets on which stingray venom acts to promote pain. Therefore, the aim of this work was to investigate some mechanisms of Potamotrygon motoro venom (PmV) that contribute to nociception induction. Evaluating spontaneous pain behavior in mice injected i.pl. with PmV, it was seen that PmV induced both neurogenic and inflammatory pain. PmV also induced hyperalgesia in both mice and rats, evaluated through electronic von Frey and rat paw pressure test, respectively. Partial inhibition of hyperalgesia was observed in mice treated with cromolyn or promethazine, which indicated that mast cell and histamine via H1 receptor participate in the inflammatory pain. To search for some targets involved in PmVinduced hyperalgesia, the participation of TRPV1, calcium channels, neurokinins, CGRP, and norepinephrine, was evaluated in rats. It was seen that PmV-induced hyperalgesia occurs with the participation of neurokinins, mainly via NK1 receptor, CGRP, and calcium influx, through both P/Q and L-type voltage-dependent calcium channels, besides TRPV1 activation. The data presented herein indicate that PmV causes hyperalgesia in rodents which is dependent on the participation of several neuroinflammatory mediators.

Potamotrygon motoro stingray venom induces both neurogenic and inflammatory pain behavior in rodents

Freshwater stingray accidents cause an immediate, intense, and unrelieved pain which is followed by edema, erythema and necrosis formation. Treatment for stingray envenomation is based on administration of analgesic, antipyretic and anti-inflammatory drugs. Concerning pain control, it is prescribed to immerse punctured limb on hot water to alleviate pain. There are no studies demonstrating specific targets on which stingray venom acts to promote pain. Therefore, the aim of this work was to investigate some mechanisms of Potamotrygon motoro venom (PmV) that contribute to nociception induction. Evaluating spontaneous pain behavior in mice injected i.pl. with PmV, it was seen that PmV induced both neurogenic and inflammatory pain. PmV also induced hyperalgesia in both mice and rats, evaluated through electronic von Frey and rat paw pressure test, respectively. Partial inhibition of hyperalgesia was observed in mice treated with cromolyn or promethazine, which indicated that mast cell and histamine via H1 receptor participate in the inflammatory pain. To search for some targets involved in PmVinduced hyperalgesia, the participation of TRPV1, calcium channels, neurokinins, CGRP, and norepinephrine, was evaluated in rats. It was seen that PmV-induced hyperalgesia occurs with the participation of neurokinins, mainly via NK1 receptor, CGRP, and calcium influx, through both P/Q and L-type voltage-dependent calcium channels, besides TRPV1 activation. The data presented herein indicate that PmV causes hyperalgesia in rodents which is dependent on the participation of several neuroinflammatory mediators.

Mast cells and histamine play an important role in edema and leukocyte recruitment induced by Potamotrygon motoro stingray venom in mice.

This work aimed to investigate mechanisms underlying the inflammatory response caused by Potamotrygon motoro stingray venom (PmV) in mouse paws. Pre-treatment of animals with a mast cell degranulation inhibitor (cromolyn) diminished edema (62% of inhibition) and leukocyte influx into the site of PmV injection. Promethazine (histamine type 1 receptor antagonist) or thioperamide (histamine type 3 and 4 receptor antagonist) also decreased edema (up to 30%) and leukocyte numbers, mainly neutrophils (40-50 %). Cimetidine (histamine type 2 receptor antagonist) had no effect on PmV-induced inflammation. In the RBL-2H3 lineage of mast cells, PmV caused proper cell activation, in a dose-dependent manner, with release of PGD2 and PGE2. In addition, the role of COXs products on PmV inflammatory response was evaluated. Indomethacin (COX-1/COX-2 inhibitor) or etoricoxib (COX-2 inhibitor) partially diminished edema (around 20%) in PmV-injected mice. Indomethacin, but not etoricoxib, modulated neutrophil influx into the site of venom injection. In conclusion, mast cell degranulation and histamine, besides COXs products, play an important role in PmV-induced reaction. Since PmV mechanism of action remains unknown, hindering accurate treatment, clinical studies can be performed to validate the prescription of antihistaminic drugs, besides NSAIDs, to patients injured by freshwater stingrays.