Estudo de efeitos tóxicos e atividades farmacológicas da fração quinona de Auxemma oncocalyx Taub

Abstract

Auxemma oncocalyx Taub. belongs to the Boraginaceae family and is native from the northeastem caatings where is know as “pau branco”. The stem bark of the tree is adstringent and popularly used in the treatment of wounds. The objective of the present work was to study toxicological effects and pharmacological activities of the hydrosoluble fraction isolated from the heartwood of A. oncocalyx. This fraction presents around 80 % of oncocalyxone A (quinone fraction). The LD50 of the quinone fraction (QF) in mice determined by the probit method was 182.16 mg/kg, i.p. and above of 500 mg/kg, o.d. The administration of QF for 15 days at the dose of 50 mg/kg, o.d. in rats, did not alter hematological or blood biochemical parameters . The pharmacological activities investigated were antiaggregating platelet, antioxidant, antiaedematogenic and antinociceptive using several experimental models. Results showed that QF presents a potent antiaggregating platelet activity in human platelets in vitro with different agonists (ADP, IC50 = 53.85 pg/ml; thrombin, IC50 = 93.76 pg/ml; collagen, IC50 = 56.57 pg/ml; arachidonic acid, IC50 = 86.07 pg/ml e adrenaline IC50 = 67.93 jig/ml). The activity was potentiated by aspirin (cyclooxynase inhibitor), pentoxifylline (methylxantine derivative and cAMP-dependent phosphodiesterase inhibitor), but not by L-arginine (NO precursor). The antiaggregating activity of QF was also observed in rat platelet in vitro in the presence of the following agonists: ADP and thrombin. However no activity was observed ex vivo. Surprisingly QF decreased bleeding time and contracted vascular smooth muscle (rat aorta). A potent antioxidant activity of QF was detected by inhibition of lipoperoxidation in rat brain homogenates, as determined by the production of substance reactive to the thiobarbituric acid (TBARS, Q1/2 = 1.64 pg/ml) and chemiluminescence (Q1Z2 = 2.06 jag/ml). However QF exerted a week activity on the model of CCl4-induced hepatotoxicity in rats as determined by measurement of ALT, AST activities and TBARS besides histopathological studies. The hepatoprotective effect of QF manifested itself more intensely in the model of prolongation by CCL4 of the barbiturate sleeping time in mice. Antinociceptive and antiedematogenic activities were also observed after QF administration, in the tests of abdominal contortion by acetic acid, formalin and hot-plate in mice (antinociceptive activity) and carrageenan and dextran-induced rat paw edema (antiedematogenic activity). The antinociceptive activity was dose-dependent, predominantly peripheric and independent of the opioid system. Results from the present work show that QF presents antiplatelet, antiinflamatory and antioxidant activities among others and these actions are probably dependent upon free radicais scavenger ability of QF.