Antispasmodic effects of the essential oil of Croton zehnteneri, anethole, and estragole, on tracheal smooth muscle.

Croton zehntneri is a plant well adapted to the semi-arid climate of northeastern region of Brazil. The essential oil of C. zehntneri (EOCz) has been described to have several pharmacologic properties, including effect on airflow resistance of in vivo respiratory system. For this reason, we investigated the hypothesis that EOCz and its major constituents, anethole and estragole, have antispasmodic activity on tracheal muscle. In tracheal rings of Wistar rats, maintained in Krebs-Henseleit's solution, EOCz, anethole and estragole inhibited contractions induced by 60mM [K+], ACh (10µM), Ba2+ and Phorbol dibutirate (1 µM). For EOCz, anethole and estragole, the IC50 for inhibition of KCl-induced contractions were 145.8 ± 14.8, 89.9 ± 7.4 and 181.0 ± 23.3 µg/mL, respectively, and for ACh-induced contraction, they were 606.1 ± 122.0, 160.5 ± 33.0 and 358.6 ± 49.2 µg/mL. Pharmacodynamic efficacy was maximal in all cases. These data in Ba2+-induced contraction and the differential IC50 suggested that blockade of Voltage Dependent Calcium Channels (VDCC) is a component of the mechanism of action of the three agents. Evaluation of the direct effect of anethole, on VDCC, showed inhibition of the Ca2+ current through this type of channel. These results show that EOCz and the constituents have antispasmodic activity and the mechanism includes blockade of VDCC channels.

Eucalyptol reduces airway hyperresponsiveness in rats following cigarette smoke-exposed.

BACKGROUND: Cigarette smoke is the major cause of airway inflammatory disease, including airway hyperresponsiveness. Eucalyptol (EUC), also named 1.8-cineole, is a monoterpenoid found in essential oil of medicinal plants, showing several biological effects. HYPOTHESIS/PURPOSE: Based in the eucalyptol protective activity in respiratory diseases as asthma, our hypothesis is that eucalyptol is able to reduce the airway hyperresponsiveness and the respiratory mechanic parameters in rats exposed to cigarette smoke. STUDY DESIGN: Wistar rats were divided into control and cigarettes smoke (CS) groups. CS group was daily subjected to cigarette smoke and treated by inhalation for 15 min/day with EUC (1 mg/mL) or vehicle during 30 days. After treatment, bronchoalveolar lavage (BAL) was collected to analyze the inflammatory profile, and tracheal rings were isolated for evaluation of the airway smooth muscle hyperresponsiveness. Lung function was analyzed in vivo. METHODS: The inflammatory profile was evaluated by optical microscopy performing total (Neubauer chamber) and differential leukocyte count (smear slides stained in H&E). The hyperresponsiveness was evaluated in tracheal rings contracted with potassium chloride (KCl) carbamoylcholine (CCh), or Barium chloride (BaCl2) in presence or absence of nifedipine. The lung function (Newtonian resistance-RN) was evaluated by bronco stimulation with methacholine (MCh). RESULTS: BAL from CS group increased the influx of leukocyte, mainly neutrophils and macrophages compared to control group. EUC reduced by 71% this influx. The tracheal contractions induced by KCl, CCh or BaCl2 were reduced by EUC in 59%, 42% and 26%, respectively. The last one was not different of nifedipine activity. Newtonian resistance (RN) was also reduced in 37% by EUC compared to CS group. CONCLUSION: EUC reduces the hyperresponsiveness and the airway inflammatory profile, recovering the lung function.

Antispasmodic effects of eugenol on rat airway smooth muscle.

This study was undertaken to assess the effects of eugenol (EUG) on tracheal muscle (TM) and the putative mechanisms underlying these effects. Cumulatively increasing concentrations (1-1000 µm) of EUG did not affect the resting tonus of TM. However, EUG (1-2000 µm) reduced the contractions induced by electrical field stimulation (IC(50) = 842.3 ± 52.7 µm), an effect that was unaltered by either 10 µm montelukast (IC(50) = 816.1 ± 70.1 µm) or 2 µm indomethacin (IC(50) = 693.1 ± 170.8 µm). EUG also completely relaxed the sustained contractile responses to 80 mM K(+) (IC(50) = 597.3 ± 60.6 µm) and 1 µm carbamoylcholine (IC(50) = 571.3 ± 148.8 µm), an effect that was unaltered by indomethacin (2 µm). Under Ca(2+) -free conditions, EUG reduced the ACh-induced contractions (IC(50) = 703.4 ± 256.1 µm), the CaCl2 -induced contractions in preparations pretreated with 60 µm ACh in the presence of nifedipine, and the Ba(2+) -induced contractions in preparations depolarized with K(+) . In tracheal preparations maintained in Ca(2+) -containing solution, EUG (300-2000 µm) relaxed the contractile response to phorbol dibutyrate (1 µm), an activator of protein kinase C. It is concluded that in TM, EUG induces a myogenic antispasmodic effect (not modulated by arachidonic acid derivatives) either through various mechanisms almost with the same pharmacological potency or via an action on a step common to all of them. These mechanisms seem to include blockade of voltage- and receptor-operated Ca(2+) channels, IP3 -induced Ca(2+) release from sarcoplasmic reticulum and reduction of the sensitivity of contractile proteins to Ca(2+) .

Ileal smooth muscle motility depression on rabbit induced by toxin A from Clostridium difficile.

This study is aimed at elucidating with in vitro experiments the time course of alteration of ileal motility caused by in vivo exposure of ligated loops of ileum to toxin A (1 microg/ligated loop) of Clostridium difficile. In the sham-operated animals no significant alteration of motility was observed. In ligated loops directly injected with toxin A and in loops neighboring those administered with this toxin, a biphasic time course of motility alterations was observed. There was initially (2 h after toxin administration) an increase in spontaneous motility and in the amplitude of maximal contraction induced by potassium and acetylcholine. Afterwards there was a progressive depression of motility, which was more severe in loops directly injected. These results suggested a significant progressive depression of rabbit ileal motility induced by toxin A from C. difficile.

Efeito da toxina A do clostridium difficile na atividade contrátil do musculo liso intestinal de coelho / The effect toxin Clostridium difficile in the contractile activity of intestinal smooth muscle of rabbit

Há na literatura uma grande lacuna a respeito dos efeitos da toxina A (TxA) do Clostridium difficile, sobre as propriedades mecânicas da musculatura lisa intestinal. Neste estudo foram avaliados os efeitos da TxA sobre as propriedades mecânicas da musculatura lisa intestinal e o mecanismo de ação. Esses efeitos foram avaliados no curso temporal de 2, 6 e 18 h, quando alças intestinais isoladas de coelho foram injetadas com 1 μg/mL/alça de TxA. Como controle interno injetamos PBS em alças isoladas, vizinhas às injetadas com TxA. O efeito do manuseio cirúrgico do protocolo experimental foi avaliado utilizando alças isoladas de coelho injetadas apenas com PBS (controle externo). Alças intestinais de animais sacrificados não submetidos à cirurgia também foram utilizadas. Foram avaliados: a amplitude da movimentação espontânea e as amplitudes das contrações fásicas induzidas por K+ (7,5 a 120 mM) e ACh (0,1 a 300 μM). Em relação à movimentação espontânea, apenas no grupo PBSp6 observou-se um aumento significativo quando comparado ao grupo SC. A TxA alterou esses parâmetros da contratilidade de maneira bifásica em relação ao curso temporal. Para os grupos TxAt18 e PBSt18, houve um escalonamento de efeitos: TxAt18 < PBSt18 < PBSt18...