European journal of pharmacology
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Methotrexate was developed as a cytostatic agent, but at low doses, it has shown potent anti-inflammatory activity. Previous studies have demonstrated that the anti-inflammatory effects of methotrexate are primarily mediated by the release of adenosine. In this study, we hypothesized that low-dose methotrexate has protective effects in spinal cord ischemia-reperfusion injury. ⋯ In contrast, both the serum and tissue catalase levels were increased. Furthermore, low-dose methotrexate treatment showed improved results concerning the histopathological scores, the ultrastructural score and the Tarlov scores. Our results revealed that low-dose methotrexate exhibits meaningful neuroprotective activity following ischemia-reperfusion injury of the spinal cord.
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Dexketoprofen and tramadol, alone or in combination, were evaluated after oral or intra-articular administration on knee osteoarthritis nociception induced by intra-articular (i.ar.) monosodium iodoacetate (MIA, 1 mg/25 µl) in the rat right knee while the left knee received saline (25 µl). Seven days after MIA treatment, dexketoprofen, tramadol, their combination or the vehicle were administered. Nociception was evaluated as alteration in hind limb weight distribution with Incapacitance tester at different time-points after drug administration. ⋯ This effect was significantly reduced by naloxone (10 μg/25 μl, i.ar.) co-administered with both compounds. The intra-articular administration of both drugs at 10 µg/25 µl in the contralateral control knee joint provoked a marked synergistic antinociceptive effect indicating significant systemic diffusion through synovial membrane. The oral or intra-articular combination of dexketoprofen and tramadol produced additive or synergistic antinociceptive effects, respectively, in the model of MIA-induced osteoarthritis in rats, that might allow to obtain therapeutic advantages with lower side effects.
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There are several studies carried out to test the effect of cholestasis on memory impairment and anxiolytic-like behaviors. Some previous studies have shown that cholestasis alters the activity of opioidergic and dopaminergic systems. The aim of the present study is however to investigate the role of mu opioid, D₁ and D₂ dopamine ventral hippocampal (CA₃) receptors upon cholestasis-induced anxiolytic-like behaviors in hole-board task. ⋯ Unlike the higher dose of SCH23390 (0.5 µg/mouse) which induced anxiogenic-like behaviors, other doses of the above drugs did not alter the exploratory behaviors in examined mice. Based on our findings, co-administration of the subthreshold dose of naloxone (0.125 µg/mouse), SCH23390 or sulpiride, and SCH23390 with sulpiride, neither altered exploratory behaviors in animals nor reversed the cholestasis-induced anxiolytic-like behaviors, seven days post BDL. Current results demonstrated firstly, the anxiolytic-like behaviors are evident in cholestatic mice seven days post BDL; secondly, there are plausible mechanisms governing the involvement of the CA₃ opioidergic and dopaminergic systems in this phenomenon and thirdly, there seem to be no interaction between these systems.
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Although carbetapentane produces skin (peripheral) infiltrative analgesia, the underlying mechanism of carbetapentane in local anesthesia is not well understood. The purpose of the study was to examine the effect of carbetapentane on voltage-gated Na(+) channels and its efficacy on spinal (central) anesthesia. We evaluated the effects of carbetapentane on rat motor and pain behavior (when administered intrathecally) and on voltage-gated sodium channels in differentiated neuronal NG108-15 cells. ⋯ Carbetapentane showed a much stronger frequency-dependence of block than lidocaine: with high frequency stimulation (3.33 Hz), 50 µM lidocaine produced an additional 30% blockade, while the same concentration of carbetapentane produced 70% more block. These results revealed carbetapentane had a more potent and prolonged spinal blockade with a more sensory/nociceptive-selective action over motor blockade in comparison with lidocaine. Spinal anesthesia with carbetapentane could be through inhibition of voltage-gated Na(+) currents.
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Resistance to ischemic acute kidney injury has been shown to be higher in female rats than in male rats. We found that renal venous norepinephrine overflow after reperfusion played important roles in the development of ischemic acute kidney injury. In the present study, we investigated whether sex differences in the pathogenesis of ischemic acute kidney injury were derived from the renal sympathetic nervous system using male and female Sprague-Dawley rats. ⋯ These sex differences were eliminated by ovariectomy or treatment with tamoxifen, an estrogen receptor antagonist, in female rats. Furthermore, an intravenous injection of hexamethonium (25mg/kg), a ganglionic blocker, 5 min before ischemia suppressed the elevation in renal venous plasma norepinephrine levels after reperfusion, and attenuated renal dysfunction and histological damage in male rats, and ovariectomized and tamoxifen-treated female rats, but not in intact females. Thus, the present findings confirmed sex differences in the pathogenesis of ischemic acute kidney injury, and showed that the attenuation of ischemia/reperfusion-induced acute kidney injury observed in intact female rats may be dependent on depressing the renal sympathetic nervous system with endogenous estrogen.