RESUMO
PURPOSE: To evaluate the effects of exposure of enoxaparin and unfractionated heparin (UFH) in prophylactic and therapeutic doses on the fertility rates of pregnant healthy Wistar rats. METHODS: Enoxaparin and UFH were administered in prophylactic doses 1 mg/Kg/day 72 UI/Kg/day, and in therapeutic doses at 2 mg/kg/day 400UI/Kg/day. The rats were divided into five groups. The number of live and dead foetuses was quantified. The uterine horns were dissected and the presence of early and late reabsorptions (abortions) was determined. A p<0.05 was considered statistically significant. RESULTS: We did not observe statistically significant differences between groups when comparing the average weight of the foetuses and placentas, rate of female VS males, rates of pre-implantation loss (RPL), rates of efficiency implantation (REI), rates of post-implantation loss (RPIL) and rates of foetal viability (RFV). CONCLUSIONS: There was no significant effect on fertility with the use of anticoagulant drugs in pregnant healthy Wistar rats. (AU)
Assuntos
Humanos , Animais , Feminino , Gravidez , Ratos , Heparina/toxicidade , Heparina/uso terapêutico , Enoxaparina/toxicidade , Enoxaparina/uso terapêutico , Fertilidade , Anticoagulantes/toxicidade , Anticoagulantes/uso terapêutico , Ratos Wistar , Trombofilia/terapia , PrenhezRESUMO
Pharmaceutical grade heparins from porcine intestine and bovine lung consist mainly of repeating tri-sulfated units, of the disaccharide â4-α-IdoA2S-1â4-α-GlcNS6S-1â. Heparin preparations from bovine intestine, in contrast, are more heterogeneous. Nuclear magnetic resonance (NMR) and disaccharide analysis after heparinase digestions show that heparin from bovine intestine contains α-glucosamine with significant substitutive variations: 64% are 6-O-sulfated and N -sulfated, as in porcine intestinal heparin while 36% are 6-desulfated. Desulfated α-iduronic acid units are contained in slightly lower proportions in bovine than in porcine heparin. NMR data also indicate N-, 3- and 6-trisulfated α-glucosamine (lower proportions) and α-GlcNS-1â4-α-GlcA and α-IdoA2S-1â4-α-GlcNAc (higher amounts) in bovine than in porcine heparin. Porcine and bovine heparins can be fractionated by anion exchange chromatography into three fractions containing different substitutions on the α-glucosamine units. Each individual fraction shows close disaccharide composition and anticoagulant activity, regardless of their origin (bovine or porcine intestine). However, these two heparins differ markedly in the proportions of the three fractions. Interestingly, fractions with the typical heparin disaccharides of porcine intestine are present in bovine intestinal heparin. These fractions contain high in vitro anticoagulant activity, reduced antithrombotic effect and high bleeding tendency. These observations indicate that the prediction of haemostatic effects of heparin preparations cannot rely exclusively on structural analysis and anticoagulant assays in vitro . Minor structural components may account for variations on in vivo effects. In conclusion, we suggest that pharmaceutical grade bovine intestinal heparin, even after purification procedures, is not an equivalent drug to porcine intestinal heparin.
Assuntos
Anticoagulantes/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Fibrinolíticos/farmacologia , Heparina/farmacologia , Mucosa Intestinal/química , Sulfatos/farmacologia , Animais , Resinas de Troca Aniônica , Anticoagulantes/química , Anticoagulantes/isolamento & purificação , Anticoagulantes/metabolismo , Anticoagulantes/toxicidade , Proteínas Antitrombina/metabolismo , Bovinos , Cromatografia por Troca Iônica , Dissacarídeos/metabolismo , Modelos Animais de Doenças , Fator Xa/metabolismo , Inibidores do Fator Xa , Feminino , Fibrinolíticos/química , Fibrinolíticos/isolamento & purificação , Fibrinolíticos/metabolismo , Fibrinolíticos/toxicidade , Glicosilação , Hemorragia/induzido quimicamente , Heparina/química , Heparina/isolamento & purificação , Heparina/metabolismo , Heparina/toxicidade , Antagonistas de Heparina/farmacologia , Heparina Liase/metabolismo , Humanos , Espectroscopia de Ressonância Magnética , Masculino , Estrutura Molecular , Tempo de Tromboplastina Parcial , Protaminas/farmacologia , Protrombina/antagonistas & inibidores , Protrombina/metabolismo , Ratos , Ratos Wistar , Relação Estrutura-Atividade , Sulfatos/química , Sulfatos/isolamento & purificação , Sulfatos/metabolismo , Sulfatos/toxicidade , Suínos , Tromboplastina , Trombose Venosa/sangue , Trombose Venosa/induzido quimicamente , Trombose Venosa/prevenção & controleRESUMO
Sulfated D-galactans occur on the red algae Botryocladia occidentalis as three fractions that differ in their sulfate content. Fractions F2 and F3 are potent anticoagulants. Like heparin, they enhance thrombin and factor Xa inhibition by antithrombin and/or heparin cofactor II. The inhibition potency increases simultaneously with the sulfate content of the fractions. The antithrombotic activity of these sulfated D-galactans was investigated on an experimental thrombosis model in which thrombus formation was induced by a combination of stasis and hypercoagulability. In contrast with heparin. the sulfated D-galactans showed a dual dose-response curve preventing thrombosis at doses up to approximately 0.5 mg/ kg body weight but losing the effect at higher doses. This unexpected behavior is probably due to a combined action of the sulfated D-galactan as anticoagulant and also as a strong inducer of platelet aggregation. In platelet-depleted animals the antithrombotic activity at higher dose of sulfated D-galactan is restored and almost total inhibition of thrombus formation is achieved. The sulfated D-galactan has no hemorrhagic effect even at high doses, possibly as a consequence of its effect on platelet aggregation. At comparable dose heparin has an intense bleeding effect. These results indicate that new polysaccharides, with well-defined structures, can help to distinguish events, such as antithrombotic and anticoagulant activities, bleeding and platelet-aggregating effects, which are obscure when induced simultaneously by a single compound.