An isoflavone from Dipteryx alata Vogel is active against the in vitro neuromuscular paralysis of Bothrops jararacussu snake venom and bothropstoxin I, and prevents venom-induced myonecrosis.

Snakebite is a neglected disease and serious health problem in Brazil, with most bites being caused by snakes of the genus Bothrops. Although serum therapy is the primary treatment for systemic envenomation, it is generally ineffective in neutralizing the local effects of these venoms. In this work, we examined the ability of 7,8,3'-trihydroxy-4'-methoxyisoflavone (TM), an isoflavone from Dipteryx alata, to neutralize the neurotoxicity (in mouse phrenic nerve-diaphragm preparations) and myotoxicity (assessed by light microscopy) of Bothrops jararacussu snake venom in vitro. The toxicity of TM was assessed using the Salmonella microsome assay (Ames test). Incubation with TM alone (200 µg/mL) did not alter the muscle twitch tension whereas incubation with venom (40 µg/mL) caused irreversible paralysis. Preincubation of TM (200 µg/mL) with venom attenuated the venom-induced neuromuscular blockade by 84% ± 5% (mean ± SEM; n = 4). The neuromuscular blockade caused by bothropstoxin-I (BthTX-I), the major myotoxic PLA2 of this venom, was also attenuated by TM. Histological analysis of diaphragm muscle incubated with TM showed that most fibers were preserved (only 9.2% ± 1.7% were damaged; n = 4) compared to venom alone (50.3% ± 5.4% of fibers damaged; n = 3), and preincubation of TM with venom significantly attenuated the venom-induced damage (only 17% ± 3.4% of fibers damaged; n = 3; p < 0.05 compared to venom alone). TM showed no mutagenicity in the Ames test using Salmonella strains TA98 and TA97a with (+S9) and without (-S9) metabolic activation. These findings indicate that TM is a potentially useful compound for antagonizing the neuromuscular effects (neurotoxicity and myotoxicity) of B. jararacussu venom.

Bioequivalence study of two commercial amoxicillin suspension formulations in healthy human volunteers.

PURPOSE: To compare the pharmacokinetic profiles and to evaluate the bioequivalence of two commercial amoxicillin suspension formulations (500 mg/5 mL AMOXIL®, reference formulation and AMOXI-PED®, test formulation) in healthy Brazilian volunteers. METHODS: Under fasting condition, 25 volunteers (13 males and 12 females) were included in this randomized, open-label, two-period crossover (1-week washout interval) bioequivalence study. Blood samples were collected at pre-dose (0 hour) and 0.5, 1, 1.33, 1.66, 2, 2.5, 3, 4, 6, 8, and 12 hours after drug ingestion. Pharmacokinetic parameters (Cmax, tmax, t1/2, AUC0-tlast, and AUC0-∞) were calculated from plasma concentrations for both formulations in each subject. RESULTS: Arithmetic mean values of the pharmacokinetic parameters were: Cmax = 12.004 (± 2.824) µg×mL-1; tmax = 1.118 (± 0.396) h; t1/2 = 1.226 (± 0.179) h; AUC0-tlast = 29.297 (± 6.007) µg×h×mL-1; and AUC0-∞ = 29.299 (± 6.007) µg×h×mL-1 for reference formulation and Cmax = 11.456 (± 2.825) µg×mL-1; tmax = 1.331 (± 0.509) h; t1/2 = 1.141 (± 0.133) h; AUC0-tlast = 28.672 (± 5.778) µg×h×mL-1; and AUC0-∞ = 28.693 (± 5.796) µg×h×mL-1 for test formulation. The confidence intervals (90% CI) for reference and test formulations were, respectively, 90.74 - 100.46% for Cmax and 93.62 - 103.61% for AUC0-t. CONCLUSION: Based on the results, both formulations of amoxicillin evaluated in this study were considered bioequivalent according to FDA and ANVISA/Brazil criteria.

Chemical constituents of the bark of Dipteryx alata vogel, an active species against Bothrops jararacussu venom.

The effect of four sub-extracts prepared from the lyophilized hydroalcoholic bark of Dipteryx alata (Leguminosae-Papilionoideae) dissolved in a methanol-water (80:20) mixture through a liquid-liquid partition procedure has been investigated against the neuromuscular blockade of the venom of the snake Bothrops jararacussu. The active CH2Cl2 sub-extract has been extensively analyzed for its chemical constituents, resulting in the isolation of four lupane-type triterpenoids: lupeol, lupenone, 28-hydroxylup-20(29)-en-3-one, betulin, nine isoflavonoids: 8-O-methylretusin, 7-hydroxy-5,6,4'-trimethoxyisoflavone, afrormosin, 7-hydroxy-8,3',4'-trimethoxyisoflavone, 7,3'-dihydroxy-8,4'-dimethoxyisoflavone, odoratin, 7,8,3'-trihydroxy-4'-methoxyisoflavone, 7,8,3'-trihydroxy-6,4'-dimethoxyisoflavone, dipteryxin, one chalcone: isoliquiritigenin, one aurone: sulfuretin and three phenolic compounds: vanillic acid, vanillin, and protocatechuic acid. Their chemical structures were elucidated on the basis of spectroscopic analysis, including HRMS, 1D- and 2D-NMR techniques.