ABSTRACT
Intracerebral haemorrhage (ICH) is a worldwide public health problem. Experimental studies have shown that oxidative stress plays an important role in the pathogenesis of ICH and could represent a target for its treatment. However, the blood-brain barrier is an obstacle to be overcome, as it hampers the administration of compounds to the central nervous system. In this study, we compared the effects of a quercetin-loaded nanoemulsion (QU-N) with the free form of the drug (QU-SP) in a collagenase-induced ICH rat model. Quercetin (QU) is a polyphenol that has an antioxidant effect in vitro, but due to its high lipophilicity, it has low bioavailability in vivo. In this study, animals submitted or not to ICH were treated with a single intraperitoneal QU dose (free or nanoemulsion) of 30 mg kg(-1). Motor assessment was evaluated by the open field, foot fault and beam walking behavioural tests. 72 h after surgery the haematoma size was evaluated and biochemical measurements were performed. Animals treated with QU-N had a significant improvement in the beam walking and open field tests. Also, QU-N was able to reduce the size of the haematoma, preserving the activity of glutathione S-transferase (GST), increasing GSH content, and the total antioxidant capacity. QU-SP recovered locomotor activity and increased the GSH content and the total antioxidant capacity. Thus, it can be observed that QU presented antioxidant activity in both formulations, but the incorporation into nanoemulsions increased its antioxidant effect, which was reflected in the improvement of the motor skills and in the haematoma size decrement. These results suggest that the nanoemulsion containing QU developed in this study could be promising for future studies on treatments for ICH.
Subject(s)
Antioxidants/administration & dosage , Cerebral Hemorrhage/drug therapy , Drug Carriers/chemistry , Nanostructures/chemistry , Quercetin/chemistry , Animals , Antioxidants/chemistry , Antioxidants/pharmacology , Body Weight/drug effects , Cerebral Hemorrhage/etiology , Chromatography, High Pressure Liquid , Collagenases/metabolism , Disease Models, Animal , Emulsions/chemistry , Glutathione/metabolism , Glutathione Transferase/metabolism , Locomotion/drug effects , Particle Size , Quercetin/administration & dosage , Quercetin/pharmacology , Rats , Rats, WistarABSTRACT
The vasorelaxing activity of the aqueous extract of fish Balistes capriscus skin (AEBc) on mesenteric arterial bed (MAB) of rats was studied. The bolus injections of AEBc (bolus of 5.1, 10.2, 20.5, and 41.1mg) significantly inhibited, in a concentration-dependent manner, the maximal contractile response induced by methoxamine (30 microM) in MAB. The vasodilatation action of AEBc is not mediated through beta-adrenoceptors or cyclo-oxigenase, since it was not affected by propranolol (20 microM) or diclofenac sodium (3 microM). The vasodilator response induced by subsequent addition of AEBc Balistes capriscus in bolus was significantly reduced in water infusion for endothelium removal. Treatment with an inhibitor of NO synthase (L-NAME, 10 microM) decreased AEBc effect. The guanylate cyclase inhibitor methylene blue (MB, 100 microM) had no significant effect on AEBc-induced vasodilatation. These results suggest that the vasorelaxing effect of AEBc is mediated by endothelium-dependent (NO/EDRF) and endothelium-independent neurally induced vasorelaxation from nonadrenergic and noncholinergic nerves (NO).
Subject(s)
Mesenteric Arteries/drug effects , Skin/chemistry , Tetraodontiformes/physiology , Vasodilation/drug effects , Vasodilator Agents/pharmacology , Adrenergic beta-Antagonists/pharmacology , Animals , Cyclooxygenase Inhibitors/pharmacology , Diclofenac/pharmacology , Dose-Response Relationship, Drug , Endothelium, Vascular/drug effects , In Vitro Techniques , Male , Methoxamine/pharmacology , Methylene Blue/pharmacology , NG-Nitroarginine Methyl Ester/pharmacology , Nitric Oxide Synthase/antagonists & inhibitors , Propranolol/pharmacology , Rats , Rats, Wistar , Vasodilator Agents/isolation & purificationABSTRACT
The effects of aqueous extracts of Ilex paraguariensis leaves (AEIp) were studied. Mesenteric arterial bed (MAB), precontracted by methoxamine with or without intact endothelium, was mounted on a tissue bath and exposed to plant extracts (bolus). The bolus injections of AEIp (300-1050 microg) significantly inhibited, in a concentration-dependent manner, the maximal contractile response induced by methoxamine (30 microm) in MAB. The endothelium-dependent relaxations were reversed by N(G)-nitro-L-arginine methyl ester (10 mM), whereas methylene blue (100 microM) was not capable of effectively inhibiting the AEIp-induced vasodilatation of MAB. The vasorelaxing effect of AEIp persisted in the presence of indomethacin (10 microM). These results suggest the involvement of NO of endothelial source (or others factors) in this vasodilatory effect.