European journal of pharmacology
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Baicalein, a pure compound derived from Scutellaria baicalensis Georgi, protected cells from lethal damage in an ischemia-reperfusion model. This study was aimed to investigate the role of opioid receptors in mediating cardioprotection by baicalein against hypoxia-reoxygenation injury. By using chick cardiomyocyte as in vitro model, baicalein was added to the perfusate during 1 h-hypoxia followed by 1 h-reoxygenation. ⋯ The cardioprotective effect of baicalein (1 microM) was blocked by pretreatment of nonspecific opioid receptor antagonist (naloxone), opioid mu-receptor (beta-funaltrexamine) and delta-receptor (7-Benzylidenenaltrexone) antagonists, protein kinase C inhibitors (H7 and chelerythrine), and KATP channel blockers (glibenclamide and 5-hydroxydecanoate). Finally, RT-PCR analysis successfully demonstrated the presence of opioid receptors mRNA in chicken embryonic cardiomyocytes. We conclude that the cardioprotective effect of baicalein is mediated via mu-, delta- but not kappa-opioid receptor and their related signal transduction pathways, such as protein kinase C and the KATP channel.
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The effect of Sivelestat, a neutrophil elastase inhibitor, on hepatic ischemia-reperfusion injury was examined in a pig hepatectomy model. An internal jugular vein-splenic vein bypass was prepared in male pigs and about 40% hepatic resection (left lobe) was performed under 15-min liver ischemia and 5-min intermittent reperfusion. Six animals received Sivelestat (10 mg/kg/h) intravenously and six control animals received physiological saline (10 mg/kg/h) from commencement of laparotomy. ⋯ Sivelestat inhibited NOS production in J774 cells, but did not inhibit expression of iNOS mRNA or TNF-alpha mRNA. In hepatic tissues, Sivelestat showed a greater tendency to inhibit expression of TNF-alpha mRNA and fewer TUNEL-positive cells were present in the hepatic sinusoidal endothelium after Sivelestat treatment, although these differences were not statistically significant. We conclude that Sivelestat inhibits production of TNF-alpha and NO by inhibiting neutrophil elastase, and thus reduces hepatic injury and stabilizes hemodynamics after ischemia-reperfusion.
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The present study was designed to investigate the ameliorative effects of clinically available drugs, with Na+/Ca2+ and Na+/H+ exchange inhibitory actions, in chronic constriction injury and vincristine induced painful neuropathy in rats. Sciatic nerve ligation and vincristine treatment (50 microg/kg for 10 days) was employed to induce neuropathy in rats. Paw pressure, von Frey hair, acetone drop, and tail heat immersion tests were performed to assess degree of mechano-hyperalgesia, mechano-allodynia, cold chemical allodynia and spinal thermal sensation respectively. ⋯ Sciatic nerve ligation and vincristine treatment resulted in significant axonal degeneration, development of mechano-hyperalgesia, mechano-allodynia, cold chemical allodynia and spinal heat hyperalgesia and also resulted in rise in thio-barbituric acid reactive species, total calcium and decrease in reduced glutathione levels. Administration of amiloride and pralidoxime attenuated chronic constriction injury and vincristine induced axonal degeneration and reduction of nociceptive threshold along with reduction in calcium levels and oxidative stress. The observed anti-nociceptive effects of amiloride and pralidoxime may possibly be attributed to inhibition of Na+/Ca2+ and Na+/H+ exchangers with subsequent decrease in Ca2+ ions and oxidative stress.
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Licorice root is used to treat asthma as a component of Shaoyao-Gancao-tang, a traditional Chinese medicine formula. In this study, we investigated the tracheal relaxation effects of isoliquiritigenin, a flavonoid isolated from the roots of Glycyrrhiza glabra (a kind of Licorice), on guinea-pig tracheal smooth muscle in vitro and in vivo. The tension changes of isolated tracheal rings were isometrically recorded on a polygraph. ⋯ Moreover, isoliquiritigenin increased by 9-fold the probability of BKCa channel openings of TSMCs in inside-out patches and markedly reduced [Ca2+]i rise induced by acetylcholine inTSMCs, pretreatment with KT5823 attenuated above two responses to isoliquiritigenin. In vivo experiment isoliquiritigenin significantly prolonged the latency time of histamine-acetylcholine aerosol-induced collapse and inhibited the increase of lung overflow induced by intravenously administered histamine dose-dependently. These data indicate that isoliquiritigenin relaxes guinea-pig trachea through a multiple of intracellular actions, including sGC activation, inhibition of PDEs, and associated activation of the cGMP/PKG signaling cascade, leading to the opening of BKCa channels and [Ca2+]i decrease through PKG-dependent mechanism and thus to tracheal relaxation.
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Hydrogen sul fi de (H2S) is an endogenous gaseous mediator, produced by cystanthionine-gamma-lysase (CSE) in the cardiovascular system. Hydrogen sulfide given before ischemia can decrease myocardial ischemia and reperfusion injury. The present study investigated: (1) if hydrogen sulfide given at early reperfusion could decrease myocardial ischemia and reperfusion injury; (2) if the protective effects of hydrogen sulfide were related to mitochondrial ATP-sensitive K+ (KATP) channels opening. ⋯ The KATP channels blocker, Glibenclamide or 5-hydroxydecanoate, reversed the cardioprotective effects of NaHS. The datum provided further evidence that exogenous H2S postconditioning protected rat heart against ischemia and reperfusion injury. Mitochondrial KATP channel opening is implicated in the postconditioning of H2S.