Comparison of venoms from wild and long-term captive Bothrops atrox snakes and characterization of Batroxrhagin, the predominant class PIII metalloproteinase from the venom of this species.

Comparisons between venoms from snakes kept under captivity or collected at the natural environment are of fundamental importance in order to obtain effective antivenoms to treat human victims of snakebites. In this study, we compared composition and biological activities of Bothrops atrox venom from snakes collected at Tapajós National Forest (Pará State, Brazil) or maintained for more than 10 years under captivity at Instituto Butantan herpetarium after have been collected mostly at Maranhão State, Brazil. Venoms from captive or wild snakes were similar except for small quantitative differences detected in peaks correspondent to phospholipases A2 (PLA2), snake venom metalloproteinases (SVMP) class PI and serine proteinases (SVSP), which did not correlate with fibrinolytic and coagulant activities (induced by PI-SVMPs and SVSPs). In both pools, the major toxic component corresponded to PIII-SVMPs, which were isolated and characterized. The characterization by mass spectrometry of both samples identified peptides that matched with a single PIII-SVMP cDNA characterized by transcriptomics, named Batroxrhagin. Sequence alignments show a strong similarity between Batroxrhagin and Jararhagin (96%). Batroxrhagin samples isolated from venoms of wild or captive snakes were not pro-coagulant, but inhibited collagen-induced platelet-aggregation, and induced hemorrhage and fibrin lysis with similar doses. Results suggest that in spite of environmental differences, venom variability was detected only among the less abundant components. In opposition, the most abundant toxin, which is a PIII-SVMP related to the key effects of the venom, is structurally conserved in the venoms. This observation is relevant for explaining the efficacy of antivenoms produced with venoms from captive snakes in human accidents inflicted at distinct natural environments.

Synthesis and biological activity of novel acridinylidene and benzylidene thiazolidinediones.

A novel set of acridinylidene thiazolidinediones and benzylidene thiazolidinediones was synthesized by nucleophilic addition of cyanoacrylates. Some of these compounds were evaluated for their glucose lowering capability and their effects on the triglyceride level in alloxan diabetic mice.

Antinociceptive and antiedematogenic effects of the aqueous extract of Hyptis pectinata leaves in experimental animals.

The aqueous leaf extract of Hyptis pectinata (L.) Poit (Lamiaceae), popularly known in Brazil as "sambaicatá" or "canudinho", was tested for its antinociceptive effects using the abdominal writhing, hot plate and formalin test models, and for its aniedematogenic effects using the carrageenin and arachidonic acid-induced rat paw edema. The aqueous extract of Hyptis pectinata administered orally at doses of 100, 200 and 400 mg/kg had a significant antinociceptive effect in the test of acetic acid-induced abdominal writhing, with 43, 51 and 54% reduction of writhes, respectively, compared to the control. An increase in hot-plate latency of 47 and 37.5% was also observed in animals receiving doses of 200 and 400 mg/kg, p.o. when placed on a hot plate. In the formalin test, doses of 200 and 400 mg/kg, p.o. had no significant effect during the first phase of the test (0-5 min), while the dose of 200 mg/kg, p.o. reduced the nociceptive effect by 70% during the second phase (20-25 min). At the dose of 600 mg/kg, p.o., the aqueous extract inhibited carrageenin-induced rat paw edema by 34.1%, and the dose of 300 mg/kg administered intraperitoneally inhibited the rat paw edema induced by subplantar injection of arachidonic acid by 32.8%. These results suggest that the aqueous extract from the Hyptis pectinata leaves produces antiedematogenic and antinociceptive effects. The antinocipetion observed with the hot-plate test probably involves the participation of the opioid system.

Anti-inflammatory, analgesic activity and acute toxicity of Sida cordifolia L. (Malva-branca).

Sida cordifolia L. (Malvaceae) is used in folk medicine for the treatment of inflammation of the oral mucosa, blenorrhea, asthmatic bronchitis and nasal congestion. The anti-inflammatory, analgesic effects and acute toxicity of an aqueous extract of S. cordifolia were evaluated in animal models. The extract was prepared using leaves collected before the flowering period. The aqueous extract (AE) showed a significant inhibition of carrageenin-induced rat paw edema at a dose of 400 mg/kg administered orally, but did not block the edema induced by arachidonic acid. The AE also increased the latency period for mice in the hot plate test, and inhibited the number of writhes produced by acetic acid at the oral dose of 400 mg/kg. The aqueous extract of S. cordifolia showed low acute toxicity in mice.

Antiinflammatory activity and acute toxicity (LD50) of the juice of Kalanchoe brasiliensis (Comb.) leaves picked before and during blooming.

Kalanchoe brasiliensis Comb. (Cassulaceae) extracts from leaves picked before and during plant blooming (extracts 1 and 2, respectively) were tested for their antiinflammatory effect on carrageenin-induced rat paw oedema and for acute toxicity (LD50). Oral doses of 0.25, 0.5 and 1.0 g/kg of extract 1 significantly inhibited the paw oedema during the first 4 h after injection of 2% carrageenin, while oral doses of 0.5, 1.0 and 2.0 g/kg of extract 2 had no inhibitory activity on the paw oedema induced by carrageenin. The results indicate an antiinflammatory effect of extract 1 and a proinflammatory effect of extract 2. K. brasiliensis extracts 1 and 2 presented no acute toxicity on mice at the doses of 0.25 to 5 g/kg administered intraperitoneally.