aconitine and Reperfusion-Injury

Activation of transient receptor potential vanilloid type 1 (TRPV1) decreases lung ischemia-reperfusion injury (LIRI) in rabbits and rats. Stimulation of α7 nicotinic acetylcholine receptors (α7nAChRs) protects against lung injury. Here we examined whether α7nAChRs contribute to TRPV1-mediated protection against LIRI.. Wild-type (WT) and TRPV1-knockout (KO) mice were subjected to 1-h lung ischemia by clamping left hilum, followed by 2-h reperfusion. WT or KO mice were pretreated with vehicle, TRPV1 agonist capsaicin, TRPV1 antagonist capsazepine, α7nAChR antagonist methyllycaconitine, or α7nAChR agonist PNU-282987. Arterial blood and lung tissues were obtained for blood gas, lung wet-to-dry weight ratio, interleukin (IL)1β, IL6, tumor necrosis factor-α (TNF-α), apoptosis-related proteins (caspases, Bax, Fas), and pathologic scoring.. TRPV1 activation alleviates LIRI, partially dependent on α7nAChR activity. The α7nAChR stimulation with or without existence of TRPV1 alleviates LIRI. Thus, α7nAChR is involved in the pathway of TRPV1-mediated protection against LIRI and the specific mechanism remains to be revealed.

Topics: Aconitine; alpha7 Nicotinic Acetylcholine Receptor; Animals; Apoptosis; Benzamides; Bridged Bicyclo Compounds; Capsaicin; Disease Models, Animal; Down-Regulation; Humans; Lung; Lung Injury; Male; Mice; Mice, Knockout; Reperfusion Injury; Treatment Outcome; TRPV Cation Channels

To observe the effects of low-intensity pulsed ultrasound (LIPUS) pretreatment on pulmonary expression of high mobility group box-1 (HMGB1) in a rat model of lung ischemia-reperfusion (IR).. LIPUS preconditioning can reduce lung IR injury possibly by activating α7nAChR-dependent cholinergic anti-inflammatory pathway to reduce lung tissue HMGB1 expression.

Topics: Aconitine; alpha7 Nicotinic Acetylcholine Receptor; Animals; HMGB1 Protein; Interleukin-1; Interleukin-6; Lung; Male; Nicotinic Antagonists; Random Allocation; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Ultrasonic Therapy; Ultrasonic Waves

Intestinal ischemia and reperfusion (I/R) is a potentially life-threatening disease, ensuing from various clinical conditions. Experimentally, either protective or detrimental roles have been attributed to 5-HT in the functional and morphological injury caused by mesenteric I/R. Recently, we proved the involvement of 5-HT2A receptors in the intestinal dysmotility and leukocyte recruitment induced by 45min occlusion of the superior mesenteric artery (SMA) followed by 24h reperfusion in mice. Starting from these premises, the aim of our present work was to investigate the role played by endogenous 5-HT in the same experimental model where 45min SMA clamping was followed by 5h reflow. To this end, we first observed that ischemic preconditioning before I/R injury (IPC+I/R) reverted the increase in 5-HT tissue content and in inflammatory parameters induced by I/R in mice. Second, the effects produced by intravenous administration of 5-HT1A ligands (partial agonist buspirone 10mgkg(-1), antagonist WAY100135 0.5-5mgkg(-1)), 5-HT2A antagonist sarpogrelate (10mgkg(-1)), 5-HT3 antagonist alosetron (0.1mgkg(-1)), 5-HT4 antagonist GR125487 (5mgkg(-1)) and 5-HT re-uptake inhibitor fluoxetine (10mgkg(-1)) on I/R-induced inflammatory response were investigated in I/R mice and compared to those obtained in sham-operated animals (S). Our results confirmed the significant role played by 5-HT2A receptors not only in the late but also in the early I/R-induced microcirculatory dysfunction and showed that blockade of 5-HT1A receptors protected against the intestinal leukocyte recruitment, plasma extravasation and reactive oxygen species formation triggered by SMA occlusion and reflow. The ability of α7 nicotinic receptor (α7nAchR) antagonist methyllycaconitine (5mgkg(-1)) to counteract the beneficial action provided by buspirone on I/R-induced neutrophil infiltration suggests that the anti-inflammatory effect produced by 5-HT1A receptor antagonism could be partly ascribed to the indirect activation of α7nAch receptors.

Topics: Aconitine; alpha7 Nicotinic Acetylcholine Receptor; Animals; Buspirone; Female; Heme Oxygenase-1; Interleukin-1beta; Intestinal Mucosa; Intestines; Malondialdehyde; Membrane Proteins; Mice; Nicotinic Antagonists; Peroxidase; Piperazines; Receptor, Serotonin, 5-HT1A; Reperfusion Injury; Serotonin; Serotonin 5-HT1 Receptor Agonists; Serotonin 5-HT1 Receptor Antagonists; Tumor Necrosis Factor-alpha

The antiarrhythmic effects of 100; 150; and 300microg/kg i.p. oxygen/ozone mixture were tested on arrhythmias induced by i) ischemia; ii) ischemia/reperfusion; iii) aconitine (15microg/kg/i.v.); potassium chloride (1.5% i.v.) in rats. 25min of cardiac left descending coronary artery ischemia caused severe incidence of ventricular tachycardia, ventricular fibrillation and mortality. These were significantly reduced by pre-treatment of rats with oxygen/ozone mixture at doses of 150 and 300microg/kg. In separate experiments using a protocol of 5min ischemia followed by 8min reperfusion this caused arrhythmias starting within 6+/-1s. The incidence of ventricular tachycardia was 100%, while ventricular fibrillation occurred in 75% of the animals and lasted 85+/-14s. The mortality was 62.5%. These figures were significantly (P<0.01) reduced in animals treated with 150microg/kg oxygen/ozone and a substantial increase observed with 300microg/kg, whilst not affected by the lower dose of 100microg/kg. 150 and 300microg/kg oxygen/ozone prolonged the onset time for the appearance of arrhythmias induced by aconitine (300microg/kg oxygen/ozone, approximately 81% longer). Oxygen/ozone also reduced the ventricular tachycardia duration, ventricular fibrillation incidence, arrhythmia score, and increased the rat's survival rate. As for example, this latter was increased from 25% (aconitine) to 50% (aconitine+oxygen/ozone 150microg/kg). 100microg/kg oxygen/ozone was without effect. None of the oxygen/ozone doses affected the arrhythmias caused by potassium chloride 1.5% i.v. All the oxygen/ozone antiarrhythmic effects were similar to those observed with lidocaine (1.5mg/kg i.v.). In conclusion, oxygen/ozone has antiarrhythmic effects against arrhythmias caused by aconitine, myocardial ischemia and ischemia/reperfusion.

Topics: Aconitine; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Male; Myocardial Ischemia; Oxygen; Ozone; Potassium Chloride; Rats; Rats, Sprague-Dawley; Reperfusion Injury