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Male SD Rats (male + sd_rat)
Selected AbstractsThe roles of prostaglandin E receptor subtypes in the cytoprotective action of prostaglandin E2 in rat stomachALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2000H. Araki Summary Aim: To investigate the EP receptor subtype involved in the gastroprotective action of prostaglandin (PG) E2 using various EP receptor agonists in rats, and using knockout mice lacking EP1 or EP3 receptors. Methods: Male SD rats and C57BL/6 mice were used after an 18-h fast. Gastric lesions were induced by oral administration of HCl/ethanol (150 m m HCl in 60% ethanol). Rats were given various EP agonists i.v. 10 min before HCl/ethanol: PGE2, sulprostone (EP1/EP3 agonist), butaprost (EP2 agonist), 17-phenyl-,-trinorPGE2 (17-phenylPGE2: EP1 agonist), ONO-NT012 (EP3 agonist) and 11-deoxyPGE1 (EP3/EP4 agonist). In a separate study, the effect of PGE2 on HCl/ethanol lesions was examined in EP1 - and EP3 -receptor knockout mice. Results: Gastric lesions induced by HCl/ethanol were dose dependently prevented by PGE2; this effect was mimicked by sulprostone and 17-phenylPGE2 and was significantly antagonized by ONO-AE-829, an EP1 antagonist. Neither butaprost, ONO-NT012 nor 11-deoxyPGE1 exhibited any protective activity against HCl/ethanol-induced gastric lesions. PGE2 caused an inhibition of gastric motility as well as an increase of mucosal blood flow and mucus secretion, the effects being mimicked by prostanoids activating EP1 receptors, EP2/EP3/EP4 receptors and EP4 receptors, respectively. On the other hand, although HCl/ethanol caused similar damage in both wild-type mice and knockout mice lacking EP1 or EP3 receptors, the cytoprotective action of PGE2 observed in wild-type and EP3 -receptor knockout mice totally disappeared in mice lacking EP1 receptors. Conclusion: The gastric cytoprotective action of PGE2 is mediated by activation of EP1 receptors. This effect may be functionally associated with inhibition of gastric motility but not with increased mucosal blood flow or mucus secretion. [source] Protective effect of Lycium barbarum on doxorubicin-induced cardiotoxicityPHYTOTHERAPY RESEARCH, Issue 11 2007Yan-Fei Xin Abstract The objective of this work was to explore the hypothesis that Lycium barbarum (LB) may be protective against doxorubicin (DOX)-induced cardiotoxicity through antioxidant-mediated mechanisms. Male SD rats were treated with distilled water or a water extract of LB (25 mg/kg, p.o.) daily and saline or DOX (5 mg/kg, i.v.) weekly for 3 weeks. Mortality, general condition and body weight were observed during the experiment. DOX-induced cardiotoxicity was assessed by electrocardiograph, heart antioxidant activity, serum levels of creatine kinase (CK) and aspartate aminotransferase (AST) and histopathological change. The DOX group showed higher mortality (38%) and worse physical characterization. Moreover, DOX caused myocardial injury manifested by arrhythmias and conduction abnormalities in ECG (increased QT and ST intervals and ST elevation), a decrease of heart antioxidant activity, an increase of serum CK and AST, as well as myocardial lesions. Pretreatment with LB significantly prevented the loss of myofibrils and improved the heart function of the DOX-treated rats as evidenced from lower mortality (13%), normalization of antioxidative activity and serum AST and CK, as well as improving arrhythmias and conduction abnormalities. These results suggested that LB elicited a typical cardioprotective effect on DOX-related oxidative stress. Furthermore, in vitro cytotoxic study showed the antitumor activity of DOX was not compromised by LB. It is possible that LB could be used as a useful adjunct in combination with DOX chemotherapy. Copyright © 2007 John Wiley & Sons, Ltd. [source] The effect of aging on distraction osteogenesis in the ratJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 3 2001J. Aronson The effect of age on bone formation in the limb lengthening model of distraction osteogenesis (DO) was investigated in two studies using Sprague,Dawley (SD) rats from two colonies at various ages (CAMM: 9 vs 24 months, Harlan: 4 vs 24 months). External fixators were placed on the right tibiae of 30 male SD rats (20 CAMM, 10 Harlan) and mid-diaphyseal osteotomies were performed. Distraction was performed at 0.2 mm bid for 20 days (CAMM) or 14 days (Harlan). The experimental (DO) and control (contra-lateral) tibiae were removed for high-resolution radiography and decalcified histology. Videomicroscopy was used to quantitate radiodensity, histology (matrix type) and relative areas of cell proliferation, which was identified by proliferating cell nuclear antigen (PCNA) immunochemistry. Both studies demonstrated an age-related decrease in the percent mineralized bone (radiodensity) in the distraction gap (CAMM 9 vs 24 months: 68% vs 51%, P < 0.003; Harlan 4 vs 24 months: 95% vs 36%, P < 0.001) and no significant colony or distraction time-specific difference was seen between the two colonies of 24-month-old rats. Histology was performed on the Harlan rats. The DO gaps in the 24-month-old rats demonstrated less endosteal new bone compared to the 4-month-old rats (P < 0.01), but equivalent periosteal new bone. In 4-month-old rats, PCNA-immunostained cells were organized along the primary matrix front (where the first deposition of osteoid occurs) extending across both periosteal and endosteal surfaces. In 24-month-old rats, PCNA + cells were organized in zones along the periosteal new bone fronts only and irregularly scattered throughout the endosteal gap within a fibrovascular non-ossifying matrix. These results indicate that 24-month-old rats have a relative deficit in endosteal bone formation which may not be related to cell proliferation but rather to cell organization. This model reflects the clinical situation where radiographic findings in older patients demonstrate significant delays in mineralization during DO. We believe this model of DO in aged rats presents unique in vivo opportunities to test hypotheses concerning (1) the effects of aging on bone repair, (2) the effects of pharmacological agents on bone repair in a geriatric setting, and (3) to study the mechanisms underlying DO. © 2001 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved. [source] Characteristic rat tissue accumulation of nobiletin, a chemopreventive polymethoxyflavonoid, in comparison with luteolinBIOFACTORS, Issue 3-4 2002Akira Murakami Abstract Nobiletin (NOB), a polymethoxyflavonoid, is an effective anti-inflammatory and chemopreventive phytochemical found in citrus fruits. We compared the absorption and metabolism characteristics of NOB with those of luteolin (LT) in male SD rats. Each flavonoid (67.1 ,mol/kg of body weight) was given separately by gastric intubation, and then concentrations were measured at 1, 4, and 24 hours after administration. In the digestive organs, NOB showed a notable tendency for localizing into the mucous membrane and muscularis from 1 to 4 hours, in contrast to LT, though both NOB and LT were completely excreted within 24 hours. Further, significant amounts of NOB were detected in the whole liver and kidney specimens, whereas LT accumulation was slight. Although serum concentrations of NOB from 1 to 4 hours were comparable to those of LT, urinary concentrations of LT were significantly higher from 4 to 24 hours. Following glucuronidase/sulfatase treatments of urinary materials, we detected 3 types of mono-demethylated NOB, including 3,-demethyl-NOB, and two di-demethylated types, as well as 3,-demethyl-NOB alone in serum samples using liquid chromatography-mass spectral analysis. Our results suggest that the metabolic properties of polymethoxyflavonoids are distinct from those of other general flavonoids, because of their wide distribution and accumulation in tissue. [source] Quantitative HPLC method and pharmacokinetic studies of ergosta-4,6,8(14),22-tetraen-3-one, a natural product with diuretic activity from Polyporus umbellatusBIOMEDICAL CHROMATOGRAPHY, Issue 10 2010Ying-Yong Zhao Abstract A simple and specific HPLC method with dual wavelength UV detection for the determination of ergosta-4,6,8(14),22-tetraen-3-one (ergone) in rat plasma was developed and proved to be efficient. The method used ergosterol as internal standard (IS). Following a single-step protein precipitation, the analyte and IS were separated on an Inertsil ODS-3 column with a mobile phase containing methanol,water (99:1, v/v) at a flow rate of 1,mL/min. The analytes were detected by using UV detection at wavelength of 350 (ergone) and 283 (IS) nm, respectively. The calibration curve was linear over the range of 0.1,2.0,µg/mL and the lower limit of quantification was 0.1,µg/mL. The intra-day and inter-day precision studies showed good reproducibility with RSD less than 8.5%. The intra-day and inter-day accuracy ranged from 95.6 to 104%. Mean extraction recovery was above 95% at the low, medium and high concentrations. The present HPLC-UV method was simple and reliable. The method described herein had been successfully applied for the pharmacokinetic studies in male SD rats after administration of 20,mg/kg dose of solution of ergone. Copyright © 2010 John Wiley & Sons, Ltd. [source] | |||||||||||||