Biological & pharmaceutical bulletin
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The present study was designed to investigate the ameliorative potential of pralidoxime in tibial and sural nerve transection-induced neuropathy in rats. Tibial and sural nerve transection was performed by sectioning tibial and sural nerve portions (2 mm) of the sciatic nerve, and leaving the common peroneal nerve intact. The pinprick, acetone, hot and cold tail immersion tests were performed to assess the degree of motor functions, mechanical hyperalgesia, cold allodynia, heat and cold hyperalgesia respectively. ⋯ However, administration of pralidoxime (10, 20 mg/kg intraperitoneally (i.p.)) for 14 d attenuated tibial and sural nerve transection-induced cold allodynia, mechanical, hot and cold hyperalgesia. Furthermore, pralidoxime also attenuated tibial and sural nerve transection induced increase in oxidative stress and calcium levels. It may be concluded that pralidoxime has ameliorative potential in attenuating the painful neuropathic state associated with tibial and sural nerve transection, which may possibly be attributed to decrease in oxidative stress and calcium levels.
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The radical scavenging effects and protective activities against oxidative stress of Korean mistletoe (Viscum album coloratum) lectin were investigated in vitro and with a cellular system using LLC-PK(1) renal epithelial cells. The Korean mistletoe lectin (KML) showed 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity with an IC(50) value of 42.6 microg/ml. It also exerted nitric oxide (NO), superoxide anion (O(2)(-)), and hydroxyl radical scavenging activities in concentration-dependent manners. ⋯ Furthermore, overexpressions of cyclooxygenase-2 and inducible NO synthase induced by SIN-1 were observed, but KML down-regulated the expression levels of both genes. KML also reduced SIN-1-induced nuclear factor kappa B expression and the phosphorylation of inhibitor kappa B alpha in LLC-PK(1) cells. These results indicate that KML has protective activities against oxidative damage induced by free radicals.
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We evaluated the cardioprotection against myocardial ischemia-reperfusion injury induced by sevoflurane postconditioning (SpostC) in chronically-infarcted rat hearts, and investigated the roles of phosphoinositide 3-kinase (PI3K)-protein kinase B/Akt (PKB/Akt), mitogen-activated extracellular regulated kinase 1/2 (MEK 1/2)-extracellular regulated kinase 1/2 (ERK 1/2), and mitochondrial permeability transition pore (mPTP). Left anterior descending (LAD) coronary artery was ligated to induce myocardial infarction in rats. Six weeks later, chronically-infarcted hearts were isolated and subjected to 30 min of global ischemia, followed by 1 h of reperfusion with Krebs-Henseleit (K-H) buffer. ⋯ We found that exposure of 3% sevoflurane during early reperfusion significantly improved functional recovery (improved left ventricular developed pressure (LVDP), +/-dp/dt, CF, HR and reduced left ventricular end-diastolic pressure (LVEDP)), decreased myocardial infarct size and reduced LDH and CK-MB release, when compared with unprotected hearts. However, these protective effects were abolished in the presence of either LY294002 or PD98059, which was accompanied by the prevention of PKB/Akt and ERK 1/2 phosphorylation, and reduction of myocardial nicotinamide adenine dinucleotide (NAD+) content. These findings suggest that sevoflurane postconditioning protects chronically-infarcted rat hearts against ischemia-reperfusion injury by inhibiting mPTP opening via recruitment of PKB/Akt and ERK 1/2.
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Cilnidipine is a 1,4-dihydropyridine-derived voltage-dependent calcium channel (VDCC) blocker and suppresses N-type VDCC currents in addition to L-type VDCC currents. An earlier investigation has suggested that intrathecally injected cilnidipine produces antinociception by blocking N-type VDCCs in mice. The present study using the rat formalin model examined antinociceptive effects of intrathecally and orally administered cilnidipine to elucidate a putative site of antinociception of cilnidipine, assess the efficacy of oral cilnidipine for pain relief, and clarify the mechanism(s) responsible for the antinociceptive effect of oral cilnidipine. ⋯ In contrast, orally administered nifedipine, an L-type VDCC blocker, had no effect on either phase of formalin-induced nociception. These results suggest that cilnidipine acts on the spinal cord to produce antinociception and is efficacious for pain relief after oral administration with better safety profile than that of ziconotide. Furthermore, the failure of orally administered nifedipine to affect formalin-induced nociception raises the possibility that oral cilnidipine produces antinociception through, at least in part, spinal N-type VDCC blockade.
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The Toll-like receptor 4 (TLR4)-mediated myeloid differentiation factor 88 (MyD88)-dependent signaling pathway plays an essential role in inflammation resulting from invading microbes. However, whether the signaling pathway is activated in the inflammatory reaction of cerebral ischemia-reperfusion and its mechanism is still unclear. In this experiment mice were randomly divided into sham group, ischemia/reperfusion group and TLR4-blocked group with different time points of reperfusion at 12, 24, 48 and 72 h. ⋯ We determined the result of TLR4 antibodies-blocking and mice cerebral ischemia-reperfusion injuries by Western blot, and evaluated neuronal damage in the hippocampus. We also determined expression of TLR4 mRNA and MyD88 mRNA by in situ hybridization (ISH), activation of nuclear factor (NF)-kappaB by electrophoretic mobility-shift analysis (EMSA), and expression of interrleukin (IL)-1beta protein by Western blot. The results demonstrated that TLR4-mediated MyD88-dependent signaling pathway activated by ischemia-reperfusion may be involved in the mechanism of ischemia-reperfusion through upregulation of NF-kappaB, IL-1beta.