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  • OPEN ACCESS
    Effects of a 24-h naproxen dose on hydration and electrolyte measures during moderate-intensity cycling in the heat
    FACETS • Vol. 2 • pp. 819 - 832
    Few controlled laboratory studies have examined the negative effects non-steroidal anti-inflammatory drugs can have on fluid–electrolyte balance during exercise. Our objective was to determine whether a 24-h naproxen dose negatively affected hydration and electrolyte measures before, during, and 3 h after 90 min of cycling in a hot or ambient environment. Using a double blind, randomized and counterbalanced cross-over design, 11 volunteers (six male, five female) completed four trials, with conditions as follows: (1) placebo and ambient, (2) placebo and heat, (3) naproxen and ambient, and (4) naproxen and heat. We found no statistically significant differences among experimental conditions for any dependent measures. Though not statistically significant, mean fluid volume was higher and urine volume was lower during naproxen trials compared with placebos. Mean aggregate plasma sodium was <135 mmol/L at all time points and did not significantly change over time. Overall plasma potassium significantly increased pre- (3.9 ± 0.4) to post-exercise (4.2 ± 0.4 mmol/L, p = 0.02). In conclusion, an acute naproxen dose did not significantly alter hydration–electrolyte balance. The trend for naproxen to increase fluid volume and decrease urine volume suggests the start of fluid retention, which should concern individuals at risk for hyponatremia or with pre-existing cardiovascular conditions.
  • OPEN ACCESS
    The beneficial effect of natural antioxidants from olive oil with fig and date palm fruit extracts on biochemical and hematological parameters in rats during diethylnitrosamine-induced carcinogenesis
    FACETS • Vol. 3 • No. 1 • pp. 584 - 597
    Diethylnitrosamine (DEN) is a well-known carcinogen. The aim of our study was to determine the role of olive oil (7 g/kg) with fig (1 g/kg) (OF) and (or) date palm (1 g/kg) (D) fruit extracts during DEN treatment of male Wistar rats. The OF–DEN and (or) D–DEN groups were given oral antioxidants daily for two weeks before and during DEN treatment (21 weeks).The DEN-treated group showed dramatic results for all investigated parameters as compared with the control rats. All OF–DEN and D–DEN groups showed significant improvement in hepatic thiobarbituric acid reactive substances, reduced glutathione, and nitric oxide concentration in the liver tissue, in addition to improvement in serum vascular endothelial growth factor level, alpha-fetoprotein, lipid profile, lipid risk ratios, and the hematological parameters as compared with the DEN-treated group.In conclusion, the administration of OF and (or) D fruit extracts to DEN-treated rats resulted in a considerable improvement in the investigated biochemical and hematological parameters. In addition, the combined OFD treatments showed greater improvements revealing the synergistic effect of the combination.
  • OPEN ACCESS
    The beneficial effect of natural antioxidants from olive oil with fig and date palm fruit extracts on biochemical and hematological parameters in rats treated with doxorubicin and γ-radiation
    FACETS • Vol. 3 • No. 1 • pp. 722 - 735
    The goal of this study was to determine the possible beneficial effect of olive oil (7 g/kg) with fig (1 g/kg) and date palm fruit (1 g/kg) extracts (OFD) on the toxicity hazards of doxorubicin (DOX) and (or) γ-radiation. The DOX-treated groups received doses of 2.5 mg/kg body weight via intravenous (IV) injection weekly for four consecutive weeks. Rats in the irradiated groups were exposed to whole-body γ-radiation with fractioned doses of 2 Gy weekly for four consecutive weeks. The OFD-treated groups received two weeks of pretreatment with OFD and daily supplementation via oral gavage during the experimental period. The DOX-treated and (or) irradiated groups showed decreases in the antioxidant parameters (reduced glutathione and nitric oxide) as well as increased lipid peroxidation products. In addition, we observed changes in the lipid profile parameters, lipid risk ratios, and hematological values (erythrocyte (RBC) count, hemoglobin (Hb) concentration, hematocrit (Hct) percentage, platelet count, and total and differential leukocyte (WBC) count) in these groups compared with the control rats. The administration of OFD to DOX-treated and (or) irradiated rats significantly ameliorated the oxidative stress markers, lipid profile, risk ratios, and hematological parameters. In conclusion, OFD could be used synergistically to decrease the negative side effects of chemotherapy and radiotherapy.
  • OPEN ACCESS
    Neuroprotective effect of Panax ginseng extract against cerebral ischemia–reperfusion-injury-induced oxidative stress in middle cerebral artery occlusion models
    FACETS • Vol. 4 • No. 1 • pp. 52 - 68
    The present study investigated the in vivo neuroprotective role of Panax ginseng extract (PGE) pretreatment against transient cerebral ischemia in a middle cerebral artery occlusion (MCAO) model. Rats were randomly divided as follows: group I, control; group II, sham-operated; group III, where animals were subjected to MCAO surgery; and group IV, where animals were orally administered 10 mL PGE per day (200 mg/kg of body weight per day) for 30 d followed by MCAO induction at day 31. Following 24 h of reperfusion, blood and tissue (brain, liver, and kidney) samples were collected for biochemical and histopathological examination. Biochemical testing included lipid profile, liver enzymes, kidney function tests, C-reactive protein (CRP), lactate dehydrogenase (LDH), glucose, and total protein estimation. Tissue antioxidants (catalase, superoxide dismutase, and glutathione) were assessed in brain, liver, and kidney tissues. MCAO-induced histopathological changes were also examined in the tissues. Pretreatment with PGE showed significant improvement in tissue antioxidant status in brain, liver and kidney tissues. PGE treatment maintains plasma lipid profile, liver enzymes, kidney function, and CRP, LDH, and glucose levels. Histologically, monocytes and macrophage infiltration were observed in the tissues of MCAO animals, whereas PGE treatment preserved tissue architecture and minimal monocyte infiltration. PGE supplementation showed a neuroprotective effect against ischemia–reperfusion injury by effectively increasing endogenous antioxidant enzyme activity.
  • OPEN ACCESS
    Pyrogenic and neuroinflammatory properties of zymosan and its potential as an alternative to live yeast in antipyretic drug testing
    FACETS • Vol. 4 • No. 1 • pp. 162 - 182
    Zymosan, an immunogenic cell wall extract of Saccharomyces cerevisiae has potential for use as an experimental pyrogen. However, the short-lived sickness responses noted with intraperitoneal and intra-articular administration of zymosan limits investigations on the long-term effectiveness of antipyretic drugs. Thus, there remains a need to establish an alternative route of zymosan administration that could induce long-lived fevers and inflammation. We injected male Sprague Dawley rats (250–300 g) subcutaneously with zymosan (30 or 300 mg/kg) or saline; n = 7–8. We measured core body temperature, cage activity, food intake and body mass for 24 h after injection. Blood and brain samples were collected at 2, 8, and 18 h after injection. Zymosan (300 mg/kg) induced fever, lethargy, and anorexia, which lasted for 24 h. Zymosan-induced sickness responses were accompanied by increased blood plasma levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α; activation of inflammatory transcription factors (nuclear factor (NF) for IL-6, signal transducer and activator of transcription (STAT)-3, and NF-κB) in the hypothalamus and circumventricular organs; and increased hypothalamic mRNA expression of TNF-α, IL-1β, and IL-6 and rate-limiting enzymes for prostaglandin synthesis. Our results confirm the suitability of subcutaneous administration of zymosan for screening antipyretic and anti-inflammatory drugs in rats.
  • OPEN ACCESS
    Relaxin peptides reduce cellular damage in cultured brain slices exposed to transient oxygen–glucose deprivation: an effect mediated by nitric oxide
    FACETS • Vol. 6 • pp. 118 - 130
    The effect of treatment with human relaxins on cell death was studied in oxygen- and glucose-deprived brain slices. In addition, involvement of nitric oxide and the relaxin receptor, RXFP3, was studied. Brain slices (n = 12–18/group) were cultured under standard conditions for two weeks and then exposed to: (i) an oxygenated balanced salt solution, (ii) a deoxygenated, glucose-free balanced salt solution (OGD media), or (iii) OGD media containing 10−7 mol/L H2 relaxin, 10−7 mol/L H2 relaxin with 50 μmol/L L-NIL, 10−7 mol/L H3 relaxin, or 10−7 mol/L H3 relaxin with 50 μmol/L L-NIL. Cell death was assessed using propidium iodide fluorescence. In a separate experiment, 10−5 mol/L R3 B1-22R (an antagonist of RXFP3) was added to both H2 and H3 relaxin treatments. H2 and H3 relaxin treatment reduced cell damage or death in OGD slices and L-NIL partially attenuated the effect of H3 relaxin. Antagonism of RXFP3 blocked the effect of H3 but not H2 relaxin. These data increase our understanding of the role of relaxin ligands and their receptors in protecting tissues throughout the body from ischemia and reperfusion injury.
  • OPEN ACCESS
    α1-adrenergic stimulation increases ventricular action potential duration in the intact mouse heart
    FACETS • Vol. 6 • pp. 823 - 836
    The role of α1-adrenergic receptors (α-ARs) in the regulation of myocardial function is less well-understood than that of β-ARs. Previous reports in the mouse heart have described that α1-adrenergic stimulation shortens action potential duration in isolated cells or tissues, in contrast to prolongation of the action potential reported in most other mammalian hearts. It has since become appreciated, however, that the mouse heart exhibits marked variation in inotropic response to α1-adrenergic stimulation between ventricles and even individual cardiomyocytes. We investigated the effects of α1-adrenergic stimulation on action potential duration at 80% of repolarization in the right and left ventricles of Langendorff-perfused mouse hearts using optical mapping. In hearts under β-adrenergic blockade (propranolol), phenylephrine or noradrenaline perfusion both increased action potential duration in both ventricles. The increased action potential duration was partially reversed by subsequent perfusion with the α-adrenergic antagonist phentolamine (1 μmol L−1). These data show that α1-receptor stimulation may lead to a prolonging of action potential in the mouse heart and thereby refine our understanding of how action potential duration adjusts during sympathetic stimulation.