Paclitaxel, a widely used cancer chemotherapeutic agent, has high incidence of neurotoxicity associated with the production of neuropathic pain, for which only duloxetine has shown significant but moderate analgesic effect. Since statins, classically used to reduce hypercholesterolemia, have shown antinociceptive effect in preclinical studies on neuropathic pain, we studied whether the antinociceptive efficacy of duloxetine could be synergistically potentiated by rosuvastatin in a model of paclitaxel-induced neuropathy in mice. The astrocytic and microglial responses in the spinal cord of paclitaxel-treated mice were also assessed by measuring GFAP and CD11b proteins, respectively.
View Article and Find Full Text PDFThe global prevalence of obesity has been steadily increasing. Although pharmacotherapy and bariatric surgeries can be useful adjuvants in the treatment of morbid obesity, they may lose long-term effectiveness. Obesity result largely from unbalanced energy homeostasis.
View Article and Find Full Text PDFBackground: Pain is one of the most common problems in clinical medicine. There is considerable evidence that pharmacologic approaches are the most widely used therapeutic options to ameliorate persistent or chronic pain. In this study it was evaluated the effect of l-NAME and naltrexone in the antinociception induced by administration of gabapentin in the orofacial formalin test of mice.
View Article and Find Full Text PDFBackground And Methods: Neuropathic pain results from nerve injury, and gabapentin, an antiepileptic drug, has been approved for the treatment of several types of neuropathic pain. On the other hand, nortriptyline, an antidepressant drug, has been suggested as an alternative treatment. In partial sciatic nerve ligation (PSNL) mice, the interaction of gabapentin with nortriptyline was evaluated by the hot plate assay using isobolographic analysis.
View Article and Find Full Text PDFNeosaxitoxin (NeoSTX) is a specific reversible blocker of voltage gated sodium channels on excitable cells. In the last decade, it has been tested in a number of interesting clinical trials, however there is still little information available on mammalian toxicity. Rats were treated for 12 weeks with doses of 1, 3 or 6 μg/kg of subcutaneous NeoSTX.
View Article and Find Full Text PDFMitochondria are key organelles for ATP production in cardiomyocytes, which is regulated by processes of fission and fusion. We hypothesized that the mitochondria fusion protein dynamin-related protein 1 (Drp1) inhibition, attenuates ischemia-reperfusion (I/R) injury through modifications in mitochondrial metabolism. Rats were subjected to I/R through coronary artery ligation, and isolated cardiomyocytes were treated with an ischemia-mimicking solution.
View Article and Find Full Text PDFBackground: The combination of two analgesic agents offers advantages in pain treatment. Codeine and morphine analgesia is due to activation of opioid receptor subtypes.
Methods: This study, performed in mice using isobolographic analysis, evaluated the type of interaction in intraperitoneal (ip) or intrathecal (it) coadministration of codeine and morphine, in three nociceptive behavioral models.
Oxidative stress and endothelial dysfunction have been associated with essential hypertension (EH) mechanisms. The purpose of this study was to evaluate the effect of carvedilol and nebivolol on the oxidative stress-related parameters and endothelial function in patients with EH. The studied population included 57 patients, either sex, between 30 and 75 years of age, with mild-to-moderate EH complications.
View Article and Find Full Text PDFOpioids have been used for long time to management of pain, the coadministration of two opioids may induce synergism. The present study was conducted to determine the antinociceptive interaction between the dual mechanism of action of tramadol compared to the main of fentanyl antinociception in the orofacial formalin which represents a model of persistent cutaneous nociception in the region innervated by the trigeminal nerve. The i.
View Article and Find Full Text PDFIt has been suggested that prenatal exposure to cadmium may alter the cardiovascular function during adulthood. Using the left coronary artery ligation model of acute myocardial infarction, we studied the cardiac function of female adult offspring rats exposed to cadmium (30 ppm) during gestation. The cardiac ischemic zone in the control and cadmium-exposed groups was measured 72 h post-ligation using the TPT staining technique.
View Article and Find Full Text PDFMitochondria are dynamic organelles able to vary their morphology between elongated interconnected mitochondrial networks and fragmented disconnected arrays, through events of mitochondrial fusion and fission, respectively. These events allow the transmission of signaling messengers and exchange of metabolites within the cell. They have also been implicated in a variety of biological processes including embryonic development, metabolism, apoptosis, and autophagy.
View Article and Find Full Text PDFBasic Clin Pharmacol Toxicol
December 2011
Statins, belonging to a well-known drug class used for lowering cholesterol through competitive inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, also have other pleiotropic properties, such as anti-inflammatory action. The purpose of this study was to evaluate the antinociceptive and anti-inflammatory effects of simvastatin in five models of nociceptive behaviour. Oral gavage administration of simvastatin induced a dose-dependent inhibition of nociception for 1 day in the acetic acid writhing (ED(50) = 5.
View Article and Find Full Text PDFSeveral cardiovascular diseases (CVD) observed in adulthood have been associated with environmental influences during fetal growth. Here, we show that maternal exposure to cadmium, a ubiquitously distributed heavy metal and main component of cigarette smoke is able to induce cardiovascular morpho-functional changes in the offspring at adult age. Heart morphology and vascular reactivity were evaluated in the adult offspring of rats exposed to 30ppm of cadmium during pregnancy.
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