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As proteins isolated from the Rhinella schneideri parotoid gland secretion (RsPP) exhibit anti-inflammatory activity, the goal of this work was to investigate their anti-nociceptive effects using acetic acid-induced writhing, formalin, and hot-plate tests. The intraperitoneal administration of RsPP (2.5 or 5 mg/kg) one hour prior to stimuli significantly reduced the abdominal constrictions induced by acetic acid (73.06 and 72.69% inhibition, respectively) and the inflammatory phase of paw licking time induced by formalin (69.3% inhibition, at 2.5 mg/kg). However, RsPP (1, 2.5 or 5 mg/kg) did not change the latency in response at the hot-plate test. The involvement of inflammatory mediators on the anti-nociceptive effect of RsPP was further demonstrated. RsPP (2.5 mg/kg) significantly inhibited the inflammatory peak of paw edema induced by histamine (44.0%), bradykinin (51.3%), or prostaglandin E2 (53.7%). Our data indicate that RsPP may act on the pain process by inhibiting the effect of inflammatory mediators.

Parotoid glands of amphibians are known for the production of several biologically active compounds having pharmacological and toxic effects in mammals. In the present work, a protein fraction obtained from Rhinella schneideri parotoid gland (RsPP) was characterized to study its biological and toxic effects. Rhinella schneideri parotoid secretion is composed of up to 30% (w/w) of soluble proteins. Tandem mass spectrometric analysis of the RsPP identified 104 proteins, including actin, beta-actin, ribosomal proteins, catalase, galectin, and uncharacterized proteins; however, no peptidases were found, and this result was reinforced by the absence of proteolytic activity. In addition, RsPP did not exhibit pro-coagulant or antibacterial effects. However, pretreatment of mice with different doses of RsPP intraperitoneally inhibited carrageenan-induced paw edema and increased tissue myeloperoxidase activity. RsPP also reduced interleukin 1β levels in the peritoneal cavities and cell migration in the peritoneal cavities of an animal model of carrageenan-induced peritonitis. Subchronic treatment of animals with RsPP for 7 consecutive days did not alter the serum biochemical, renal, or liver parameters. However, a significant reduction in blood leukocyte count was observed. Our results showed that R. schneideri parotoid secretion contains proteins with anti-inflammatory and slight toxic effects.