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Sample records for rats oral administration

  1. Clonic Seizures in GAERS Rats after Oral Administration of Enrofloxacin

    Science.gov (United States)

    Bauquier, Sebastien H; Jiang, Jonathan L; Lai, Alan; Cook, Mark J

    2016-01-01

    The aim of this study was to evaluate the effect of oral enrofloxacin on the epileptic status of Genetic Absence Epilepsy Rats from Strasbourg (GAERS). Five adult female GAERS rats, with implanted extradural electrodes for EEG monitoring, were declared free of clonic seizures after an 8-wk observation period. Enrofloxacin was then added to their drinking water (42.5 mg in 750 mL), and rats were observed for another 3 days. The number of spike-and-wave discharges and mean duration of a single discharge did not differ before and after treatment, but 2 of the 5 rats developed clonic seizures after treatment. Enrofloxacin should be used with caution in GAERS rats because it might induce clonic seizures. PMID:27298247

  2. Metabolism and incorporation of orally administrated arachidonic acid in rats

    International Nuclear Information System (INIS)

    Magni, F.; Kikawa, Y.; Jedlinski, A.; Lands, W.E.M.

    1986-01-01

    50 mg 3 H 2 H-20: 4n-6 was administered by oral intubation to rats maintained on a normal diet. The distribution of radioactive arachidonate esterified in the various tissues was similar to that for EFA-deficient rats from their previous study. The amount incorporated in the tissues was 14% in normal rats and 16% in EFA-deficient rats. At 24 hrs, the relative radioactivity in PC was higher (and lower in PE) than after 20 days in the previous study. Urine had 3-4% of initial radioactivity in the first 12 hours and only 1% more by 24 hours. Urine components were analyzed as methyl ester-methoxime-t-butyldimethylsilyl ethers. Most of the arachidonate metabolites in urine reported in the literature have expected ECL values between 26 to 32, whereas they found 68% of radioactivity with ECL values below 26. This represents a substantial divergence from arachidonate metabolite patterns described for injected prostaglandins and indicates the need of examining the metabolites formed from endogenously formed eicosanoids

  3. Oral administration of piperine for the control of aflatoxin intoxication in rats.

    Science.gov (United States)

    Gagini, Thalita B; Silva, Robson E; Castro, Isabela S; Soares, Breno A; Lima, Marco E F; Brito, Marilene F; Mazur, Carlos; Direito, Glória M; Danelli, Maria das Graças M

    2010-04-01

    Aflatoxins are mycotoxins that have important toxic effects on human and animal health, even if consumed at low doses. The oral administration of piperine (1.12 mg/kg) during 23 days in rats seemingly interfered with the toxicity of aflatoxins, decreasing hepatic injuries and the leukocyte depletion in experimentally intoxicated animals.

  4. Comparative pharmacokinetics of arctigenin in normal and type 2 diabetic rats after oral and intravenous administration.

    Science.gov (United States)

    Zeng, Xiao-yan; Dong, Shu; He, Nan-nan; Jiang, Chun-jie; Dai, Yue; Xia, Yu-feng

    2015-09-01

    Arctigenin is the main active ingredient of Fructus Arctii for the treatment of type 2 diabetes. In this study, the pharmacokinetics of arctigenin in normal and type 2 diabetic rats following oral and intravenous administration was investigated. As compared to normal rats, Cmax and AUC(0-10h) values of oral arctigenin in diabetic rats increased by 356.8% and 223.4%, respectively. In contrast, after intravenous injection, the Cmax and AUC(0-10h) values of arctigenin showed no significant difference between diabetic and normal rats. In order to explore how the bioavailability of oral arctigenin increased under diabetic condition, the absorption behavior of arctigenin was evaluated by in situ single-pass intestinal perfusion (SPIP). The results indicated that arctigenin was a substrate of P-glycoprotein (P-gp). The absorption difference of arctigenin in the normal and diabetic rats could be eliminated by the pretreatment of classic P-gp inhibitor verapamil, suggesting that P-gp might be the key factor causing the absorption enhancement of arctigenin in diabetic rats. Further studies revealed that the uptake of rhodamine 123 (Rho123) in diabetic rats was significantly higher, indicating that diabetes mellitus might impair P-gp function. Consistently, a lower mRNA level of P-gp in the intestine of diabetic rats was found. In conclusion, the absorption of arctigenin after oral administration was promoted in diabetic rats, which might be partially attribute to the decreased expression and impaired function of P-gp in intestines. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Effect of Oral Administration of “Gadagi” Tea on Lipid Profile in Rats ...

    African Journals Online (AJOL)

    Abstract: Effect of oral administration of “Gadagi” tea on lipid profile was assessed in 50 healthy male albino rats which were grouped and administered with different doses(mg/kg) i.e low dose (380mg/kg, 415mg/kg, 365mg/kg,. 315mg/kg for “sak”, ”sada” and “magani” respectively), standard dose (760mg/kg, 830mg/kg, ...

  6. Pharmacokinetics of /sup 3/H-pipethiaden after single oral and intravenous administration in rats

    Energy Technology Data Exchange (ETDEWEB)

    Lapka, R.; Franc, Z.; Smolik, S.

    1985-01-01

    Tritium labelled anti-migraine drug 4-(1-methyl-4-piperidyliden)-4,9-duhydrothieno(2,3-c)-2-benzothiepine (pipethiaden) was prepared. After oral and intravenous administration to rats not only the courses of total radioactivity in plasma and various organs were determined, but by means of TLC-radiometry also the levels of pipethiaden itself. After the oral dose 1.35 mg/kg the plasma levels of pipethiaden did not exceed 3.5 ng/ml. Some pharmacokinetic parameters (e.g. t/sub 1/2/el-4h) were calculated by compartmental analysis of plasma levels.

  7. Combined oral administration of bovine collagen peptides with calcium citrate inhibits bone loss in ovariectomized rats.

    Science.gov (United States)

    Liu, JunLi; Wang, YiHu; Song, ShuJun; Wang, XiJie; Qin, YaYa; Si, ShaoYan; Guo, YanChuan

    2015-01-01

    Collagen peptides (CPs) and calcium citrate are commonly used as bone health supplements for treating osteoporosis. However, it remains unknown whether the combination of oral bovine CPs with calcium citrate is more effective than administration of either agent alone. Forty 12-week-old Sprague-Dawley rats were randomly divided into five groups (n = 8) for once-daily intragastric administration of different treatments for 3 months at 3 months after ovariectomy (OVX) as follows: sham + vehicle; OVX + vehicle; OVX + 750 mg/kg CP; OVX + CP-calcium citrate (75 mg/kg); OVX + calcium citrate (75 mg/kg). After euthanasia, the femurs were removed and analyzed by dual energy X-ray absorptiometry and micro-computed tomography, and serum samples were analyzed for bone metabolic markers. OVX rats supplemented with CPs or CP-calcium citrate showed osteoprotective effects, with reductions in the OVX-induced decreases in their femoral bone mineral density. Moreover, CP-calcium citrate prevented trabecular bone loss, improved the microarchitecture of the distal femur, and significantly inhibited bone loss with increased bone volume, connectivity density, and trabecular number compared with OVX control rats. CP or CP-calcium citrate administration significantly increased serum procollagen type I N-terminal propeptide levels and reduced serum bone-specific alkaline phosphatase, osteocalcin, and C-telopeptide of type I collagen levels. Our data indicate that combined oral administration of bovine CPs with calcium citrate inhibits bone loss in OVX rats. The present findings suggest that combined oral administration of bovine CPs with calcium citrate is a promising alternative for reducing bone loss in osteopenic postmenopausal women.

  8. Combined oral administration of bovine collagen peptides with calcium citrate inhibits bone loss in ovariectomized rats.

    Directory of Open Access Journals (Sweden)

    JunLi Liu

    Full Text Available Collagen peptides (CPs and calcium citrate are commonly used as bone health supplements for treating osteoporosis. However, it remains unknown whether the combination of oral bovine CPs with calcium citrate is more effective than administration of either agent alone.Forty 12-week-old Sprague-Dawley rats were randomly divided into five groups (n = 8 for once-daily intragastric administration of different treatments for 3 months at 3 months after ovariectomy (OVX as follows: sham + vehicle; OVX + vehicle; OVX + 750 mg/kg CP; OVX + CP-calcium citrate (75 mg/kg; OVX + calcium citrate (75 mg/kg. After euthanasia, the femurs were removed and analyzed by dual energy X-ray absorptiometry and micro-computed tomography, and serum samples were analyzed for bone metabolic markers.OVX rats supplemented with CPs or CP-calcium citrate showed osteoprotective effects, with reductions in the OVX-induced decreases in their femoral bone mineral density. Moreover, CP-calcium citrate prevented trabecular bone loss, improved the microarchitecture of the distal femur, and significantly inhibited bone loss with increased bone volume, connectivity density, and trabecular number compared with OVX control rats. CP or CP-calcium citrate administration significantly increased serum procollagen type I N-terminal propeptide levels and reduced serum bone-specific alkaline phosphatase, osteocalcin, and C-telopeptide of type I collagen levels.Our data indicate that combined oral administration of bovine CPs with calcium citrate inhibits bone loss in OVX rats. The present findings suggest that combined oral administration of bovine CPs with calcium citrate is a promising alternative for reducing bone loss in osteopenic postmenopausal women.

  9. Evaluation of Cardiopulmonary Toxicity Following Oral Administration of Multi-walled Carbon Nanotubes in Wistar Rats

    Directory of Open Access Journals (Sweden)

    Ehsan Zayerzadeh

    2016-07-01

    Full Text Available Objective(s: Carbon nanotubes have unique mechanical, electrical, and thermal properties, with potential different applications in nanomedicine, electronics, and other industries. These new applications of carbon nanotubes in different industries lead to the increased exposure risk of nanomaterials to human. Up to now, all aspects of carbon nanotubes toxicity are not completely clear following human and animal exposures with these novel compounds. The aim of this study was to assess cardiopulmonary toxicity of multi-walled carbon nanotubes following oral administration in rats with respect to the histopathological and biochemical evaluation. Methods: In the present investigation, we studied cardiorespiratory toxicity of multi-wall carbon nanotubes (MWCNT with regard to histopathological changes and some biomarkers including TnT, CK-MB and LDH in experimental rats following oral administration. One dose per 24 h of MWCNT suspension was administered orally (gavage technique to animals at the doses of 500, 1000 and 2000 mg/kg/day BW for 5 days. Results: The results of these study showed oral administration of MWCNT induces histopathological complications such as severe alveolar edema and hemorrhage in lungs and myocytolysis in heart of all experimental groups of animals. In all of the groups, troponin T level showed no changes when compared to baseline. Lactate dehydrogenase and CK-MB activity showed significant increment in all of animal groups following oral administration of carbon nanotubes. Conclusions: It can be concluded that oral exposure of MWCNT may be toxic for cardiovascular and respiratory systems, because MWCNT induced biochemical alterations and histopathological abnormalities in these vital systems.

  10. Excretion and metabolism of 1-nitropyrene in rats after oral or intraperitoneal administration

    International Nuclear Information System (INIS)

    Dutcher, J.S.; Sun, J.D.; Bechtold, W.E.; Unkefer, C.J.

    1985-01-01

    The metabolism and excretion of 1-nitropyrene (NP), a prevalent NPAH, by Fischer-344 rats after intraperitoneal (ip) or oral administration was studied. Radiolabeled NP was administered to rats (10 mg NP/kg body wt), and urine and feces were collected for 7 days. After ip administration of [ 14 C]NP, 60% of the radioactivity was found in the urine and 20% in the feces. Likewise, 55 and 35% of the orally administered 14 C was found in urine and feces, respectively. Both urine and feces were analyzed by high-pressure liquid chromatography for metabolites. The majority of the radioactivity in both urine and feces was associated with very polar metabolites, none accounting for more than 10% of the dose. Small amounts (less than 1% of the dose) of aminopyrene (AP), acetylaminopyrene, and NP were detected. A urinary metabolite (3-8% of the dose) was found that converted to acetylaminopyrene phenol (two isomers) when urine was heated overnight at 37 0 C at pH 4.5. More of this metabolite (2.2 times) as well as AP (1.8 times), was excreted after oral than after ip administration of NP. The NP metabolites found in this study demonstrate that reduction of the nitro group is a significant route of NP metabolism in rats. Since nitroreduction appears to be necessary in the activation of NPAHs to bacterial mutagens, this indicates that similar metabolic pathways are present in rats (catalyzed by mammalian and/or gut bacterial enzymes) and that activation of NPAHs to carcinogens or toxins by nitroreduction is possible. 29 references, 8 figures

  11. Regulation of operant oral ethanol self-administration: a dose-response curve study in rats.

    Science.gov (United States)

    Carnicella, Sebastien; Yowell, Quinn V; Ron, Dorit

    2011-01-01

    Oral ethanol self-administration procedures in rats are useful preclinical tools for the evaluation of potential new pharmacotherapies as well as for the investigation into the etiology of alcohol abuse disorders and addiction. Determination of the effects of a potential treatment on a full ethanol dose-response curve should be essential to predict its clinical efficacy. Unfortunately, this approach has not been fully explored because of the aversive taste reaction to moderate to high doses of ethanol, which may interfere with consumption. In this study, we set out to determine whether a meaningful dose-response curve for oral ethanol self-administration can be obtained in rats. Long-Evans rats were trained to self-administer a 20% ethanol solution in an operant procedure following a history of excessive voluntary ethanol intake. After stabilization of ethanol self-administration, the concentration of the solution was varied from 2.5 to 60% (v/v), and operant and drinking behaviors, as well as blood ethanol concentration (BEC), were evaluated following the self-administration of a 20, 40, and 60% ethanol solution. Varying the concentration of ethanol from 2.5 to 60% after the development of excessive ethanol consumption led to a typical inverted U-shaped dose-response curve. Importantly, rats adapted their level and pattern of responding to changes in ethanol concentration to obtain a constant level of intake and BEC, suggesting that their operant behavior is mainly driven by the motivation to obtain a specific pharmacological effect of ethanol. This procedure can be a useful and straightforward tool for the evaluation of the effects of new potential pharmacotherapies for the treatment of alcohol abuse disorders. Copyright © 2010 by the Research Society on Alcoholism.

  12. Oral metformin-ascorbic acid co-administration ameliorates alcohol-induced hepatotoxicity in rats.

    Science.gov (United States)

    Adeneye, A A; Benebo, A S

    2007-01-01

    Alcoholic liver disease remains a major cause of liver failure worldwide with no available curative or prophylactic therapy as at present. High dose metformin is reported to ameliorate liver injuries in both human and animal models of acute and chronic alcoholic liver injuries. The aim of the present in vivo animal study was to determine whether metformin-ascorbic acid co-administration also prevents alcoholic hepatotoxicity in chronic alcohol exposure. In the present study, ameliorating effect of 200 mg/ kg/day of ascorbic acid (Asc), 500 mg/kg/day of metformin (Met) and their co-administration (Met-Asc) were investigated in 5 groups of 50% ethanol-treated male Wistar rats for 2 weeks of the experiment. The body weight of each rat was taken on days 1, 7, and 14 of the experiment, respectively. On day 15, fasted blood samples for plasma lipids and liver enzyme markers were collected via cardiac puncture from the rats under diethyl ether anaesthesia. Results showed that administration of graded oral doses of 50% ethanol for 14 days significantly (pcholesterol (PTC), high density lipoprotein (HDL-c), and low density lipoprotein (LDL-c). However, these elevations were significantly (pascorbic acid co-administration protected the liver against the deleterious effects of chronic high dose alcohol and the hepatoprotective effect of Met-Asc appeared to be due mainly to the metformin molecule of the drug combination. However, further studies would be required to evaluate the mechanisms underlying the observed effects.

  13. Oral administration of amphotericin B nanoparticles: antifungal activity, bioavailability and toxicity in rats.

    Science.gov (United States)

    Radwan, Mahasen A; AlQuadeib, Bushra T; Šiller, Lidija; Wright, Matthew C; Horrocks, Benjamin

    2017-11-01

    Amphotericin B (AMB) is used most commonly in severe systemic life-threatening fungal infections. There is currently an unmet need for an efficacious (AMB) formulation amenable to oral administration with better bioavailability and lower nephrotoxicity. Novel PEGylated polylactic-polyglycolic acid copolymer (PLGA-PEG) nanoparticles (NPs) formulations of AMB were therefore studied for their ability to kill Candida albicans (C. albicans). The antifungal activity of AMB formulations was assessed in C. albicans. Its bioavalability was investigated in nine groups of rats (n = 6). Toxicity was examined by an in vitro blood hemolysis assay, and in vivo nephrotoxicity after single and multiple dosing for a week by blood urea nitrogen (BUN) and plasma creatinine (PCr) measurements. The MIC of AMB loaded to PLGA-PEG NPs against C. albicans was reduced two to threefold compared with free AMB. Novel oral AMB delivery loaded to PLGA-PEG NPs was markedly systemically available compared to Fungizone® in rats. The addition of 2% of GA to the AMB formulation significantly (p bioavailability from 1.5 to 10.5% and the relative bioavailability was > 790% that of Fungizone®. The novel AMB formulations showed minimal toxicity and better efficacy compared to Fungizone®. No nephrotoxicity in rats was detected after a week of multiple dosing of AMB NPs based on BUN and PCr, which remained at normal levels. An oral delivery system of AMB-loaded to PLGA-PEG NPs with better efficacy and minimal toxicity was formulated. The addition of glycyrrhizic acid (GA) to AMB NPs formulation resulted in a significant oral absorption and improved bioavailability in rats.

  14. Effect of age on the pharmacokinetics of polymorphic nimodipine in rats after oral administration

    DEFF Research Database (Denmark)

    Liu, Wenli; Wang, Xiaona; Chen, Ruilian

    2016-01-01

    The previous investigation has proved that their existed pharmacokinetic difference between the different crystal forms of the polymorphic drugs after oral administration. However, no systemic investigations have been made on the change of this pharmacokinetic difference, resulted either from...... and 3.06 in 9-month-old rats. Since age difference could result in unparallelled change of the absorption and bioavailability of the polymorphic drugs, the results in this experiment are of value for further investigation of crystal form selection in clinical trials and rational clinical application...

  15. Oral administration of synthetic human urogastrone promotes healing of chronic duodenal ulcers in rats

    DEFF Research Database (Denmark)

    Poulsen, Steen Seier; Nexø, Ebba

    1986-01-01

    The effect of oral administration of synthetic human epidermal growth factor/urogastrone (EGF/URO) on healing of chronic duodenal ulcers induced by cysteamine in rats was investigated and compared with that of cimetidine, a H2-receptor antagonist. After 25 and 50 days of treatment, synthetic human...... EGF/URO significantly increased healing of chronic duodenal ulcers to the same extent as cimetidine. Combined treatment with synthetic human EGF/URO and cimetidine for 25 days was more effective than synthetic human EGF/URO given alone, whereas combined treatment for 50 days was significantly more...... human EGF/URO is a potent inhibitor of gastric acid secretion when administered intravenously, but had no effect on acid secretion when given intraduodenally, which suggests that the effect of synthetic human EGF/URO is a direct action on the duodenal mucosa. In conclusion, this study showed that oral...

  16. Effect of oral administration of terephthalic acid on testicular functions of rats

    International Nuclear Information System (INIS)

    Cui Lunbiao; Dai Guidong; Xu Lichun; Wang Shouling; Song Ling; Zhao Renzhen; Xiao Hang; Zhou Jianwei; Wang Xinru

    2004-01-01

    To investigate the toxic effect of terephthalic acid (TPA) on testicular functions of rats, male Sprague-Dawley rats were orally administered TPA in diet at the levels 0 (control), 0.2, 1 and 5% for 90 days. Testicular functions were assessed by histopathology, testicular sperm head counts, daily sperm production, sperm motility (measured by computer-assisted sperm analysis, CASA), biochemical indices (marker testicular enzymes), and serum testosterone. Oral feeding with terephthalic acid did not cause body and testes weight loss in TPA-treated groups. Histopathologically, damages of spermatogenic cells and Sertoli cells were observed by electron microscope, testicular sperm head counts, daily sperm production, and activities of sorbitol dehydrogenase (SDH) were decreased significantly in the 5% TPA group. The motility of spermatozoa was reduced significantly in all treated groups, which was correlated with administration doses. Serum testosterone concentrations were not declined in treated groups. In conclusion, TPA can cause impairment of testicular functions. The primary sites of action may be spermatogenic cells and Sertoli cells. The results of the present study provide first information of TPA on testicular functions in male rats

  17. Toxicokinetics and biotransformation of 3-(4-methylbenzylidene)camphor in rats after oral administration

    International Nuclear Information System (INIS)

    Voelkel, Wolfgang; Colnot, Thomas; Schauer, Ute M.D.; Broschard, Thomas H.; Dekant, Wolfgang

    2006-01-01

    3-(4-Methylbenzylidene)camphor (4-MBC) is an UV-filter frequently used in sunscreens and cosmetics. Equivocal findings in some screening tests for hormonal activity initiated a discussion on a possible weak estrogenicity of 4-MBC. In this study, the toxicokinetics and biotransformation of 4-MBC were characterized in rats after oral administration. Male and female Sprague-Dawley rats (n = 3 per group) were administered single oral doses of 25 or 250 mg/kg bw of 4-MBC in corn oil. Metabolites formed were characterized and the kinetics of elimination for 4-MBC and its metabolites from blood and with urine were determined. Metabolites of 4-MBC were characterized by 1 H NMR and LC-MS/MS as 3-(4-carboxybenzylidene)camphor and as four isomers of 3-(4-carboxybenzylidene)hydroxycamphor containing the hydroxyl group located in the camphor ring system with 3-(4-carboxybenzylidene)-6-hydroxycamphor as the major metabolite. After oral administration of 4-MBC, only very low concentrations of 4-MBC were present in blood and the peak concentrations of 3-(4-carboxybenzylidene)camphor were approximately 500-fold above those of 4-MBC; blood concentrations of 3-(4-carboxybenzylidene)-6-hydroxycamphor were below the limit of detection. Blood concentration of 4-MBC and 3-(4-carboxybenzylidene)camphor peaked within 10 h after 4-MBC administration and then decreased with half-lives of approximately 15 h. No major differences in peak blood levels between male and female rats were seen. In urine, one isomer of 3-(4-carboxybenzylidene)hydroxycamphor was the predominant metabolite [3-(4-carboxybenzylidene)-6-hydroxycamphor], the other isomers and 3-(4-carboxybenzylidene)camphor were only minor metabolites excreted with urine. However, urinary excretion of 4-MBC-metabolites represents only a minor pathway of elimination for 4-MBC, since most of the applied dose was recovered in feces as 3-(4-carboxybenzylidene)camphor and, to a smaller extent, as 3-(4-carboxybenzylidene)-6-hydroxycamphor

  18. Oral and nasal administration of chicken type II collagen suppresses adjuvant arthritis in rats with intestinal lesions induced by meloxicam.

    Science.gov (United States)

    Zheng, Yong-Qiu; Wei, Wei; Shen, Yu-Xian; Dai, Min; Liu, Li-Hua

    2004-11-01

    To investigate the curative effects of oral and nasal administration of chicken type II collagen (CII) on adjuvant arthritis (AA) in rats with meloxicam-induced intestinal lesions. AA model in Sprague-Dawley (SD) rats with or without intestinal lesions induced by meloxicam was established and those rats were divided randomly into six groups which included AA model, AA model+meloxicam, AA model+oral CII, AA model+nasal CII, AA model+ meloxicam+oral C II and AA model+meloxicam+nasal CII (n = 12). Rats was treated with meloxicam intragastrically for 7 d from d 14 after immunization with complete Freund's adjuvant (CFA), and then treated with chicken CII intragastrically or nasally for 7 d. Histological changes of right hind knees were examined. Hind paw secondary swelling and intestinal lesions were evaluated. Synoviocyte proliferation was measured by 3-(4,5-dimethylthiazol-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide (MTT) method. Activities of myeloperoxidase (MPO) and diamine oxidase (DAO) from supernatants of intestinal homogenates were assayed by spectrophotometric analysis. Intragastrical administration of meloxicam (1.5 mg/kg) induced multiple intestinal lesions in AA rats. There was a significant decrease of intestinal DAO activities in AA+meloxicam group (P<0.01) and AA model group (P<0.01) compared with normal group. DAO activities of intestinal homogenates in AA+meloxicam group were significantly less than those in AA rats (P<0.01). There was a significant increase of intestinal MPO activities in AA+meloxicam group compared with normal control (P<0.01). Oral or nasal administration of CII (20 microg/kg) could suppress the secondary hind paw swelling(P<0.05 for oral CII; P<0.01 for nasal CII), synoviocyte proliferation (P<0.01) and histopathological degradation in AA rats, but they had no significant effects on DAO and MPO changes. However, oral administration of CII (20 microg/kg) showed the limited efficacy on arthritis in AA+meloxicam model and the

  19. Toxicokinetics of the ciguatoxin P-CTX-1 in rats after intraperitoneal or oral administration.

    Science.gov (United States)

    Bottein, Marie-Yasmine Dechraoui; Wang, Zhihong; Ramsdell, John S

    2011-06-18

    Ciguatoxins are voltage-gated selective algal toxins responsible for ciguatera fish poisoning. In this study we evaluate the toxicokinetics of one of the most common ciguatoxins found in the Pacific, the P-CTX-1, in rat after an oral or intraperitoneal (ip) dose of 0.26 μg/kg body weight. We report levels of ciguatoxin activity assessed over time in blood, urine and feces, and at 4 days in liver, muscle and brain, using the functional in vitro N2A cytotoxicity assay. Following exposure, the ciguatoxin activity exhibited a rapid systemic absorption that was followed by a bi-exponential decline, and data best fit a two-compartment model analysis. Maximum blood concentrations were reached at 1.97 and 0.43 h after the oral and ip dose, respectively. Ciguatoxin elimination from blood was slow with terminal half lives (t(½)β) estimated at 82 h for oral and 112 h for ip dosing. Ciguatoxin activity remained in liver, muscle and brain 96 h after ip and oral administration. While smaller amounts appeared in the urine, the main excretion route was feces, with peak rates reaching > 10 pg P-CTX-1 equivalents/h in both routes of administration. Assay guided fractionation showed the presence in the feces and liver of peaks of activity corresponding to the P-CTX-1 and to other less polar metabolites. In conclusion, biologically active ciguatoxins are detectable in blood, liver, muscle and brain, and continued to be excreted in urine and feces 4 days following exposure. Blood, as well as urine and feces may be useful matrices for low-invasive testing methods for ciguatera clinical cases. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  20. Pharmacokinetics of oxiracetam and its degraded substance (HOPAA after oral and intravenous administration in rats

    Directory of Open Access Journals (Sweden)

    Xinhuan Wan

    2014-12-01

    Full Text Available The pharmacokinetics of oxiracetam and its degraded substance (4-hydroxy-2-oxo-1-pyrrolidine acetic acid, HOPAA after oral and intravenous administration in rats were studied using an established UPLC-MS/MS method. Three groups of rats after an overnight fasted received 10 g/kg (n = 6 oxiracetam suspensions orally, and 2 g/kg (n = 6 normal or degraded oxiracetam injections intravenously via a caudal tail vein, respectively. Before the pharmacokinetic experiment, a simple safety evaluation test was conducted on the degraded oxiracetam injections containing 16.16% HOPAA in mice. There was no mortality by a single intravenous dose of 2 g/kg of degraded oxiracetam injections within two weeks, demonstrating that HOPAA was non-toxic in mice. Following intravenous administration of the normal injections, the plasma concentration-time curves of oxiracetam and HOPAA both showed a rapid elimination phase. The values of t1/2 were 3.1 ± 1.5 h for oxiracetam and 0.8 ± 0.2 h for HOPAA, and the mean residence times (MRT were 1.2 ± 0.1 h and 0.8 ± 0.1 h, respectively. Oxiracetam and HOPAA after intravenous administration of the degraded oxiracetam injections presented elimination patterns similar to those observed in the normal injections. Oral pharmacokinetic results showed that the Tmax was less than 1.5 h for the two analytes, and both had a longer t1/2 and MRT than those of intravenous administration. Contents of HOPAA in three groups were calculated based on AUC0–t values of the two analytes. The quantitative change of HOPAA in vivo was also evaluated by comparing the plasma concentrations of HOPAA and oxiracetam at the same time for every group. Additionally, the values of absolute bioavailability of oxiracetam were about 8.0% and 7.4% calculated by the normal or degraded oxiracetam injections, which were far less than the value of 75% reported in literature, indicating the necessity of further study.

  1. Changes in plasma glucose in Otsuka Long-Evans Tokushima Fatty rats after oral administration of maple syrup.

    Science.gov (United States)

    Nagai, Noriaki; Yamamoto, Tetsushi; Tanabe, Wataru; Ito, Yoshimasa; Kurabuchi, Satoshi; Mitamura, Kuniko; Taga, Atsushi

    2015-01-01

    We investigate whether maple syrup is a suitable sweetener in the management of type 2 diabetes using the Otsuka Long-Evans Tokushima Fatty (OLETF) rat. The enhancement in plasma glucose (PG) and glucose absorption in the small intestine were lower after the oral administration of maple syrup than after sucrose administration in OLETF rats, and no significant differences were observed in insulin levels. These data suggested that maple syrup might inhibit the absorption of glucose from the small intestine and preventing the enhancement of PG in OLETF rats. Therefore, maple syrup might help in the prevention of type 2 diabetes.

  2. Effects of prolonged oral administration of fumonisin B1 and aflatoxin B1 in rats.

    Science.gov (United States)

    Pozzi, C R; Corrêa, B; Xavier, J G; Direito, G M; Orsi, R B; Matarazzo, S V

    2001-01-01

    The effects of prolonged oral administration (21 days) of fumonisin B1 (FB1) and aflatoxin B1 (AFB1) were evaluated on male Wistar rats. The animals were housed in individual metabolic cages and submitted to the following treatments: 1-0 microg AFB1 + 0 mg FB1/100g bw.; 2-72 microg AFB1+ 0 mg FB1/100 g bw; 3-0 microg AFB1 + 0.5 mg FB1 g bw; 4-0 microg AFB1 + 1.5 mg FB1/100 g bw; 5-72 microg AFB1 + 0.5 mg FB1/100g bw; 6-72 microgAFB1 + 1.5 mg FB1/100g bw. On day 21, the rats were sacrificed for evaluation. The results showed that treated animals presented differences in body weight and absolute/relative weights of liver and kidney as well as altered hepatic function and cholesterol blood levels. Rats fed with the greatest doses of AFB1 and FB1 gained less weight (2.79 g/day) at the end of the experimental period; their blood concentrations of liver enzymes aspartate aminotransferase (AST) and alkaline phosphatase (AP) were above control levels (130.35 micro/l and 471.00 micro/l, respectively). Blood cholesterol increased in the groups treated with the highest dose of FB1 or FB1 associated with AFB1. Histopathology revealed the occurrence of apoptosis in the liver of rats exposed to FB1. The association of aflatoxin B1 with fumonisin B1 at higher dose probably potentiated the effects of the higher dose of fumonisin B1 acting singly.

  3. Absorption, distribution, metabolism and excretion of selenium following oral administration of elemental selenium nanoparticles or selenite in rats

    DEFF Research Database (Denmark)

    Löschner, Katrin; Hadrup, Niels; Hansen, Marianne

    2014-01-01

    A suspension of nanoparticles of BSA-stabilized red amorphous elemental selenium (Se) or an aqueous solution of sodium selenite was repeatedly administered by oral gavage for 28 days at 0.05 mg/kg bw/day (low dose) or at 0.5 mg/kg bw/day (high dose) as Se to female rats. Prior to administration...

  4. Pharmacokinetic interaction of enrofloxacin/trimethoprim combination following single-dose intraperitoneal and oral administration in rats.

    Science.gov (United States)

    Choi, Myung-Jin; Yohannes, Sileshi Belew; Lee, Seung-Jin; Damte, Dereje; Kim, Jong-Choon; Suh, Joo-Won; Park, Seung-Chun

    2014-03-01

    The pharmacokinetic interaction of enrofloxacin and trimethoprim was evaluated after single-dose intraperitoneal or oral co-administration in rats. Plasma concentrations of the two drugs were determined by high-performance liquid chromatography. Following intraperitoneal combination, a significant (P trimethoprim, respectively. There was a significant (P trimethoprim. Further study is recommended in other species of animals.

  5. Tissue distribution of berberine and its metabolites after oral administration in rats.

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    Xiang-Shan Tan

    Full Text Available Berberine (BBR has been confirmed to have multiple bioactivities in clinic, such as cholesterol-lowering, anti-diabetes, cardiovascular protection and anti- inflammation. However, BBR's plasma level is very low; it cannot explain its pharmacological effects in patients. We consider that the in vivo distribution of BBR as well as of its bioactive metabolites might provide part of the explanation for this question. In this study, liquid chromatography coupled to ion trap time-of-flight mass spectrometry (LC/MS(n-IT-TOF as well as liquid chromatography that coupled with tandem mass spectrometry (LC-MS/MS was used for the study of tissue distribution and pharmacokinetics of BBR in rats after oral administration (200 mg/kg. The results indicated that BBR was quickly distributed in the liver, kidneys, muscle, lungs, brain, heart, pancreas and fat in a descending order of its amount. The pharmacokinetic profile indicated that BBR's level in most of studied tissues was higher (or much higher than that in plasma 4 h after administration. BBR remained relatively stable in the tissues like liver, heart, brain, muscle, pancreas etc. Organ distribution of BBR's metabolites was also investigated paralleled with that of BBR. Thalifendine (M1, berberrubine (M2 and jatrorrhizine (M4, which the metabolites with moderate bioactivity, were easily detected in organs like the liver and kidney. For instance, M1, M2 and M4 were the major metabolites in the liver, among which the percentage of M2 was up to 65.1%; the level of AUC (0-t (area under the concentration-time curve for BBR or the metabolites in the liver was 10-fold or 30-fold higher than that in plasma, respectively. In summary, the organ concentration of BBR (as well as its bioactive metabolites was higher than its concentration in the blood after oral administration. It might explain BBR's pharmacological effects on human diseases in clinic.

  6. Absorption, Distribution, Metabolism and Excretion of 3-MCPD 1-Monopalmitate after Oral Administration in Rats.

    Science.gov (United States)

    Gao, Boyan; Liu, Man; Huang, Guoren; Zhang, Zhongfei; Zhao, Yue; Wang, Thomas T Y; Zhang, Yaqiong; Liu, Jie; Yu, Liangli

    2017-03-29

    Fatty acid esters of monochloropropane 1,2-diol (3-MCPD) are processing-induced toxicants and have been detected in several food categories. This study investigated the absorption, distribution, metabolism, and excretion of 3-MCPD esters in Sprague-Dawley (SD) rats using 3-MCPD 1-monopalmitate as the probe compound. The kinetics of 3-MCPD 1-monopalmitate in plasma was investigated using SD rats, and the results indicated that 3-MCPD 1-monopalmitate was absorbed directly in vivo and metabolized. Its primary metabolites in the liver, kidney, testis, brain, plasma, and urine were tentatively identified and measured at 6, 12, 24, and 48 h after oral administration. Structures were proposed for eight metabolites. 3-MCPD 1-monopalmitate was converted to free 3-MCPD, which formed the phase II metabolites. All of the metabolites were chlorine-related chemical components; most of them existed in urine, reflecting the excretion pattern of 3-MCPD esters. Understanding the metabolism of 3-MCPD esters in vivo is critical for assessing their toxicities.

  7. Tissue distribution and elimination after oral and intravenous administration of different titanium dioxide nanoparticles in rats

    Science.gov (United States)

    2014-01-01

    Objective The aim of this study was to obtain kinetic data that can be used in human risk assessment of titanium dioxide nanomaterials. Methods Tissue distribution and blood kinetics of various titanium dioxide nanoparticles (NM-100, NM-101, NM-102, NM-103, and NM-104), which differ with respect to primary particle size, crystalline form and hydrophobicity, were investigated in rats up to 90 days post-exposure after oral and intravenous administration of a single or five repeated doses. Results For the oral study, liver, spleen and mesenteric lymph nodes were selected as target tissues for titanium (Ti) analysis. Ti-levels in liver and spleen were above the detection limit only in some rats. Titanium could be detected at low levels in mesenteric lymph nodes. These results indicate that some minor absorption occurs in the gastrointestinal tract, but to a very limited extent. Both after single and repeated intravenous (IV) exposure, titanium rapidly distributed from the systemic circulation to all tissues evaluated (i.e. liver, spleen, kidney, lung, heart, brain, thymus, reproductive organs). Liver was identified as the main target tissue, followed by spleen and lung. Total recovery (expressed as % of nominal dose) for all four tested nanomaterials measured 24 h after single or repeated exposure ranged from 64-95% or 59-108% for male or female animals, respectively. During the 90 days post-exposure period, some decrease in Ti-levels was observed (mainly for NM-100 and NM-102) with a maximum relative decrease of 26%. This was also confirmed by the results of the kinetic analysis which revealed that for each of the investigated tissues the half-lifes were considerable (range 28–650 days, depending on the TiO2-particle and tissue investigated). Minor differences in kinetic profile were observed between the various particles, though these could not be clearly related to differences in primary particle size or hydrophobicity. Some indications were observed for an

  8. Inhibition of rat microsomal lipid peroxidation by the oral administration of D002

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    Menéndez R.

    2000-01-01

    Full Text Available The effect of D002, a defined mixture of higher primary alcohols purified from bee wax, on in vivo and in vitro lipid peroxidation was studied. The extent of lipid peroxidation was measured on the basis of the levels of thiobarbituric acid reactive substances (TBARS. When D002 (5-100 mg/kg body weight was administered orally to rats for two weeks, a partial inhibition of the in vitro enzymatic and non-enzymatic lipid peroxidation was observed in liver and brain microsomes. Maximal protection (46% occurred at a dose of 25 mg/kg. D002 behaved differently depending on both the presence of NADPH and the integrity of liver microsomes, which suggests that under conditions where microsomal metabolism was favored the protective effect of D002 was increased. D002 (25 mg/kg also completely inhibited carbon tetrachloride- and toluene-induced in vivo lipid peroxidation in liver and brain. Also, D002 significantly lowered in a dose-dependent manner the basal level of TBARS in liver (19-40% and brain (28-44% microsomes. We conclude that the oral administration of D002 (5, 25 and 100 mg/kg for two weeks protected rat liver and brain microsomes against microsomal lipid peroxidation in vitro and in vivo. Thus, D002 could be useful as a dietary natural antioxidant supplement. More studies are required before these data can be extrapolated to the recommendation for the use of D002 as a dietary antioxidant supplement for humans.

  9. Positive Foci of Glutathione S‐Transferase Placental Form in the Liver of Rats Given Furfural by Oral Administration

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    Shimizu, Akio; Nakamura, Yoshiyasu; Harada, Masaoki; Ono, Tetsuo; Sato, Kiyomi; Inoue, Tohru; Kanisawa, Masayoshi

    1989-01-01

    We observed GST‐P‐positive liver foci in rats during the course of developing liver cirrhosis by oral administration of furfural, an organic solvent. Male Wistar rats were given furfural‐containing diet (20–30 rag/kg diet) for 15–150 days, and killed 14 days after terminating furfural feeding. Immuno‐histochemical investigation of GST‐P‐positive liver foci which appeared in rats fed furfural for more than 30 days revealed an increase in number and size of the foci in proportion to the duration of furfural administration. Since furfural is known not to be carcinogenic in rats, this finding will be helpful to understand the enhancing effect of furfural‐induced cirrhosis on chemical hepatocarcino‐genesis. PMID:2507483

  10. Pharmacokinetics of Stereoisomeric Dipeptide Prodrugs of Acyclovir Following Intravenous and Oral Administrations in Rats: A Study Involving In vivo Corneal Uptake of Acyclovir Following Oral Dosing

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    Ravi S.Talluri

    2009-10-01

    Full Text Available Objective: To delineate the plasma pharmacokinetics and determine the corneal uptake of valine based stereoisomeric dipeptide prodrugs of acyclovir (ACV in rats. Methods: Male Sprague-Dawley rats were used for the study. Pharmacokinetics of ACV, L-valine-acyclovir (LACV, L-valine- D-valine-acyclovir (LDACV and D-valine-L-valine acyclovir (DLACV prodrugs were delineated. These compounds were administered intravenously as a bolus via jugular vein cannula and orally by gavage. Samples were purified by protein precipitation method and analyzed by LC-MS/MS. Pertinent pharmacokinetic parameters were obtained by using WinNonlin. Corneal uptake studies of LDACV and LACV were studied following oral administration. Results: Following i.v. administration, the area under the curve (AUC in µM*min of generated ACV was in the order of LACV › LDACV › DLACV indicating their rate of metabolism. The AUC values of total drug obtained in the systemic circulation after oral administration LACV and LDACV were 1077.93 ± 236.09 and 1141.76 ± 73.67 µM*min, respectively. DLACV exhibited poor oral absorption. Cmax (µM and AUC of the intact prodrug obtained in the systemic circulation following oral administration of LDACV were almost 4–5 times higher than LACV. Moreover, concentrations achieved in the cornea after oral administration of LDACV were almost two times of LACV. Conclusions: LDACV increased both the oral bioavailability and subsequent in vivo corneal uptake of ACV. Hence, LDACV can be considered as the most promising drug candidate for delivery of ACV, in treatment of both genital herpes and ocular herpes keratitis after oral administration.

  11. Pharmacokinetics of Stereoisomeric Dipeptide Prodrugs of Acyclovir Following Intravenous and Oral Administrations in Rats: A Study Involving In vivo Corneal Uptake of Acyclovir Following Oral Dosing

    Science.gov (United States)

    Talluri, Ravi S.; Gaudana, Ripal; Hariharan, Sudharshan; Mitra, Ashim K.

    2009-01-01

    Objective To delineate the plasma pharmacokinetics and determine the corneal uptake of valine based stereoisomeric dipeptide prodrugs of acyclovir (ACV) in rats. Methods Male Sprague-Dawley rats were used for the study. Pharmacokinetics of ACV, L-valine-acyclovir (LACV), L-valine-D-valine-acyclovir (LDACV) and D-valine-L-valine acyclovir (DLACV) prodrugs were delineated. These compounds were administered intravenously as a bolus via jugular vein cannula and orally by gavage. Samples were purified by protein precipitation method and analyzed by LC-MS/MS. Pertinent pharmacokinetic parameters were obtained by using WinNonlin. Corneal uptake studies of LDACV and LACV were studied following oral administration. Results Following i.v. administration, the area under the curve (AUC) in μM*min of generated ACV was in the order of LACV > LDACV > DLACV indicating their rate of metabolism. The AUC values of total drug obtained in the systemic circulation after oral administration LACV and LDACV were 1077.93 ± 236.09 and 1141.76 ± 73.67 μM*min, respectively. DLACV exhibited poor oral absorption. Cmax (μM) and AUC of the intact prodrug obtained in the systemic circulation following oral administration of LDACV were almost 4–5 times higher than LACV. Moreover, concentrations achieved in the cornea after oral administration of LDACV were almost two times of LACV. Conclusions LDACV increased both the oral bioavailability and subsequent in vivo corneal uptake of ACV. Hence, LDACV can be considered as the most promising drug candidate for delivery of ACV, in treatment of both genital herpes and ocular herpes keratitis after oral administration. PMID:23861607

  12. Pharmacokinetics of Stereoisomeric Dipeptide Prodrugs of Acyclovir following Intravenous and Oral Administrations in Rats: A study Involving in vivo corneal Uptake of Acyclovir following Oral Dosing

    Directory of Open Access Journals (Sweden)

    Ravi S. Talluri

    2009-01-01

    Full Text Available Objective To delineate the plasma pharmacokinetics and determine the corneal uptake of valine based stereoisomeric dipeptide prodrugs of acyclovir (ACV in rats. Methods Male Sprague-Dawley rats were used for the study. Pharmacokinetics of ACV, L-valine-acyclovir (LACV, L-valine-D-valine-acyclovir (LDACV and D-valine-L-valine acyclovir (DLACV prodrugs were delineated. These compounds were administered intravenously as a bolus via jugular vein cannula and orally by gavage. Samples were purified by protein precipitation method and analyzed by LC-MS/MS. Pertinent pharmacokinetic parameters were obtained by using WinNonlin. Corneal uptake studies of LDACV and LACV were studied following oral administration. Results Following i.v. administration, the area under the curve (AUC in μM*min of generated ACV was in the order of LACV > LDACV > DLACV indicating their rate of metabolism. The AUC values of total drug obtained in the systemic circulation after oral administration LACV and LDACV were 1077.93 ± 236.09 and 1141.76 ± 73.67 μM*min, respectively. DLACV exhibited poor oral absorption. C max (μM and AUC of the intact prodrug obtained in the systemic circulation following oral administration of LDACV were almost 4–5 times higher than LACV. Moreover, concentrations achieved in the cornea after oral administration of LDACV were almost two times of LACV. Conclusions LDACV increased both the oral bioavailability and subsequent in vivo corneal uptake of ACV Hence, LDACV can be considered as the most promising drug candidate for delivery of ACV, in treatment of both genital herpes and ocular herpes keratitis after oral administration.

  13. Pharmacokinetics and dosimetry of the anti-androgen vinclozolin after oral administration inthe rat

    Science.gov (United States)

    Vinclozolin (V) is a fungicide with antiandrogenic properties. To determine the pharmacokinetics and dosimetry of V, adult male rats were administered an oral dose of V (100 mg/kg) in corn oil and sacrificed over time after dosing. V and its metabolites were analyzed in serum and...

  14. Acute oral administration of low doses of methylphenidate targets calretinin neurons in the rat septal area.

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    Alvaro eGarcía-Aviles

    2015-03-01

    Full Text Available Methylphenidate (MPD is a commonly administered drug to treat children suffering from attention deficit hyperactivity disorder (ADHD. Alterations in septal driven hippocampal theta rhythm may underlie attention deficits observed in these patients. Amongst others, the septo-hippocampal connections have long been acknowledged to be important in preserving hippocampal function. Thus, we wanted to ascertain if methylphenidate administration, which improves attention in patients, could affect septal areas connecting with hippocampus. We used low and orally administered methylphenidate doses (1.3; 2.7 and 5mg/Kg to rats what mimics the dosage range in humans. In our model, we observed no effect when using 1.3mg/Kg methylphenidate; whereas 2.7 and 5 mg/Kg induced a significant increase in c-fos expression specifically in the medial septum, an area intimately connected to the hippocampus. We analyzed dopaminergic areas such as nucleus accumbens and striatum, and found that only 5mg/Kg induced c-fos levels increase. In these areas tyrosine hydroxylase correlated well with c-fos staining, whereas in the medial septum the sparse tyrosine hydroxylase fibres did not overlap with c-fos positive neurons. Double immunofluorescence of c-fos with neuronal markers in the septal area revealed that co-localization with choline acethyl transferase, parvalbumin, and calbindin with c-fos did not change with MPD treatment; whereas, calretinin and c-fos double labeled neurons increased after MPD administration. Altogether, these results suggest that low and acute doses of methylphenidate primary target specific populations of caltretinin medial septal neurons.

  15. Oral Administration of Shark Type II Collagen Suppresses Complete Freund’s Adjuvant-Induced Rheumatoid Arthritis in Rats

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    Wenhui Wu

    2012-03-01

    Full Text Available Objective: Shark type II collagen (SCII is extracted as a glycoprotein from the cartilage of blue shark (Prionace glauca. We aim to confirm the effects of oral tolerance of SCII on inflammatory and immune responses to the ankle joint of rheumatoid-arthritis rats induced by Complete Freund’s Adjuvant (CFA. Materials and Methods: The onset of rheumatoid arthritis (RA was observed 14 ± x days after injection of CFA. Rats in the control group were treated with acetic acid by oral administration (0.05 mmol kg−1d−1, days 14–28, while rats in experimental groups were treated by oral administration with SCII (1 or 3 mg kg−1d−1, days 14–28, Tripterygium wilfordii polyglycosidium (TWP (10 mg kg−1d−1, days 14–28, and bovine type II collagen from US (US-CII (1 mg kg−1d−1, days 14–28, respectively. The severity of arthritis was evaluated by the articular swelling. The immunological indexes observed included delayed type hypersensitivity (DTH reaction, the level of interleukins 10 (IL-10 in rat blood serum and morphological characterization. Mixed lymphocyte culture (MLC was performed to investigate the relationship between T cell apoptosis and specific immune tolerance induced by SCII. Results: Treatment with SCII for 2 weeks significantly attenuated the acute inflammation. The rats orally administrated with SCII at the level of 3 mg kg−1d−1 (SCII 3 and US-CII had decreased DTH reaction compared with rats in control group. Rats treated with SCII 3 had the highest level of IL-10 with 102 pg/mL. SCII with concentration of 10 μg/L could help to significantly enhance level of Fas/Apo-1 in T cell in vitro. The result of histological staining indicated that the recovery of the articular membranes of ankle joint in SCII 3 group was greatly enhanced. Conclusions: Our results suggest that appropriate dose of SCII can not only ameliorate symptoms but also modify the disease process of Complete-Freunds-Adjuvant-induced arthritis. Oral

  16. Toxicologic evaluation of acute and subacute oral administration of Cucurbita maxima seed extracts to rats and swine.

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    de Queiroz-Neto, A; Mataqueiro, M I; Santana, A E; Alessi, A C

    1994-06-01

    The extract prepared from dried seeds of Cucurbita maxima was administered to rats and pigs. Following a single dose or 4 weeks of daily oral administration, the extract produced no changes in serum glucose, urea, creatinine, total protein, uric acid, GOT, GPT, LDH or blood counts. Urine analysis (urea, uric acid, creatinine, total protein, Na and K), as well as histopathological investigation, showed no abnormalities. These results taken as a whole indicate that the seeds of C. maxima as used in Brazilian folk medicine are not toxic for rats and swine.

  17. Antihypertensive effects of continuous oral administration of nattokinase and its fragments in spontaneously hypertensive rats.

    Science.gov (United States)

    Fujita, Mitsugu; Ohnishi, Katsunori; Takaoka, Shinsaku; Ogasawara, Kazuya; Fukuyama, Ryo; Nakamuta, Hiromichi

    2011-01-01

    To determine whether the antihypertensive effect of nattokinase is associated with the protease activity of this enzyme, we compared nattokinase with the fragments derived from nattokinase, which possessed no protease activity, in terms of the effect on hypertension in spontaneously hypertensive rats (SHR). In the continuous oral administration test, the groups were given a basic diet alone (control), the basic diet containing nattokinase (0.2, 2.6 mg/g diet) or the basic diet containing the fragments derived from nattokinase (0.2, 0.6 mg/g diet). The group fed the basic diet containing high-dosage nattokinase (2.6 mg/g diet) showed significant reductions in systolic blood pressure (SBP), diastolic blood pressure (DBP) and plasma fibrinogen level, compared with control group and no influence on activities of renin and angiotensin-converting enzyme (ACE, EC 3.4.15.1), and plasma angiotensin II level in the renin-angiotensin system. The treatment of the basic diet containing high-dosage fragments (0.6 mg/g diet) significantly decreased SBP, DBP and plasma angiotensin II level in plasma but the treatment did not influence on plasma fibrinogen level. These results suggest that nattokinase and its fragments are different from each other in the mechanism to reduce hypertension. Nattokinase, retained its protease activity after absorbance across the intestines, may decrease blood pressure through cleavage of fibrinogen in plasma. The fragments, which absorbed as nattokinase-degradation products, prevents the elevation of plasma angiotensin II level to suppress hypertension.

  18. Contrasting Nephropathic Responses to Oral Administration of Extract of Cultured Penicillium polonicum in Rat and Primate

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    John E. Fincham

    2010-08-01

    Full Text Available Liquid- or solid substrate-cultured Penicillium polonicum administered in feed to rats over several days evokes a histopathological response in kidney involving apoptosis and abnormal mitosis in proximal tubules. The amphoteric toxin is yet only partly characterized, but can be isolated from cultured sporulating biomass in a fraction that is soluble in water and ethanol, and exchangeable on either anion- or cation-exchange resins. After several weeks of treatment renal proximal tubule distortion became striking on account of karyocytomegaly, but even treatment for nearly two years remained asymptomatic. Extract from a batch of solid substrate fermentation of P. polonicum on shredded wheat was incorporated into feed for rats during four consecutive days, and also given as an aqueous solution by oral gavage to a vervet monkey daily for 10 days. Treatment was asymptomatic for both types of animal. Rat response was evident as the typical renal apoptosis and karyomegaly. In contrast there was no such response in the primate; and neither creatinine clearance nor any haematological characteristic or serum component concentration deviated from a control or from historical data for this primate. The contrast is discussed concerning other negative findings for P. polonicum in pigs and hamsters. Renal karyomegaly, as a common rat response to persistent exposure to ochratoxin A, is not known in humans suspected as being exposed to more than the usual trace amounts of dietary ochratoxin A. Therefore the present findings question assumptions that human response to ochratoxin A conforms to that in the rat.

  19. The antinociceptive effects of Monechma ciliatum and changes in EEG waves following oral and intrathecal administration in rats

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    Meraiyebu, Ajibola B.; Adelaiye, Alexander B.; O, Odeh S.

    2010-02-01

    The research work was carried out to study the effect of Oral and Intrathecal Monechma Ciliatum on antinociception and EEG readings in Wistar Rats. Traditionally the extract is given to women in labour believed to reduce pain and ease parturition, though past works show that it has oesteogenic and oxytotic effects. The rats were divided into 5 major groups. Group 1 served as oral control group while groups 2 and 3 served as oral experimental groups and were treated with 500mg/kg and 1000mg/kg monechma ciliatum respectively. Group 4 served as intrathecal control group treated with intrathecal dextrose and group 5 received 1000mg/kg Monechma Ciliatrum intrathecally. The antinociceptive effect was analysed using a Von Frey's aesthesiometer. Monechma Ciliatum showed significant antinociceptive effect both orally and intrathecally, although it had a greater effect orally and during the first 15 minutes of intrathecal administration. EEG readings were also taken for all the groups and there was a decrease in amplitude and an increase in frequency for high dose (1000mg/ml) experimental groups and the mid brain electrodes produced a change from theta waves (3.5 - 7 waves per second) to alpha waves (7.5 - 13 waves per second) as seen in relaxed persons and caused decreased amplitudes and change in distribution seen in beta waves. Properties similarly accentuated by sedativehypnotic drugs.

  20. Pharmacokinetics and Biodistribution of Aurantiamide and Aurantiamide Acetate in Rats after Oral Administration of Portulaca oleracea L. Extracts.

    Science.gov (United States)

    Chen, Lijiang; Liu, Yang; Jia, Dechao; Yang, Jia; Zhao, Jinhua; Chen, Changlan; Liu, Hongsheng; Liang, Xiao

    2016-05-04

    Aurantiamide and aurantiamide acetate are the main active constituents of purslane (Portulaca oleracea L.), an edible plant with various biological activities. In this study, we developed a validated UHPLC-MS/MS method to quantitate the concentrations of aurantiamide and aurantiamide acetate in the plasma and various organ tissues of rat as the basis to study their pharmacological profile and distribution in vivo. Aurantiamide and aurantiamide acetate were rapidly absorbed following oral administration, both achieving a Cmax at around 0.2 h. The extent of their metabolisms also varied among different organ tissues, resulting in about 90% reduction in concentrations 4 h after their administration, thus leaving no long-term accumulation in the tissues. This is the first study to examine the pharmacokinetic and biodistribution of aurantiamide and aurantiamide acetate in rat, and our work may serve as the first step toward the investigation of the underlying mechanisms associated with the biological activity of purslane.

  1. Comparative pharmacokinetics of swertiamarin in rats after oral administration of swertiamarin alone, Qing Ye Dan tablets and co-administration of swertiamarin and oleanolic acid.

    Science.gov (United States)

    Xu, Gui-li; Li, Hong-liang; He, Jian-chang; Feng, En-fu; Shi, Pan-pan; Liu, Yue-qiong; Liu, Chang-xiao

    2013-08-26

    Qing Ye Dan is a well-known herbal drug that is widely used to treat viral hepatitis in the Yi and Hani minority regions in the Yunnan province of China. An LC-MS/MS method was developed to determine the levels of swertiamarin in rat plasma. Swertiamarin and naringin (internal standard, IS) were extracted from rat plasma using solid-phase extraction (SPE) to purify the samples. The pharmacokinetics of the following different administration methods of swertiamarin in rats were studied: oral administration of swertiamarin alone, a Qing Ye Dan tablet (QYDT) and co-administration of swertiamarin and oleanolic acid, with each method delivering approximately 20mg/kg of swertiamarin. Non-compartmental pharmacokinetic profiles were constructed by using the software DAS (version 2.1.1), and the pharmacokinetic parameters were compared using an unpaired Student's t-test. The results showed that the pharmacokinetic parameters Cmax, AUC0-∞, Vz/F and CLz/F were significantly different (P<0.05) among the three types of swertiamarin administration. The data indicate that oleanolic acid and the other ingredients present in QYDT could affect the pharmacokinetic behaviour of swertiamarin in rats. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  2. Evaluation of the subchronic toxicity of kefir by oral administration in Wistar rats.

    Science.gov (United States)

    Diniz Rosa, Damiana; Gouveia Peluzio, Maria do Carmo; Pérez Bueno, Tania; Vega Cañizares, Ernesto; Sánchez Miranda, Lilian; Mancebo Dorbignyi, Betty; Chong Dubí, Dainé; Espinosa Castaño, Ivette; Marcin Grzes Kowiak, Lukasz; Fortes Ferreira, Célia Lucia de Luces

    2014-06-01

    Kefir is obtained by fermentation of milk with complex microbial populations present in kefir grains. Several health-promoting benefits have been attributed to kefir consumption. The objective of this work was to conduct a subchronic toxicity study, offering the rats normal or high-doses of kefir and evaluating growth, hematology and blood chemistry, as well as assessing bacterial translocation and the integrity of the intestinal mucosa of animals. Wistar rats were randomly divided into three groups (n = 6/group): control group received 0.7 mL of water, kefir group received 0.7 mL/day of kefir, (normodose), and Hkefir group received 3.5 mL/day of kefir (fivefold higher dose). Feeding was carried out by gavage. The animals were housed in individual cages and maintained under standard conditions for 4 weeks. The normodose and high-dose of kefir supplementation did not harm the animals since growth, hematology and blood chemistry in rats, as well as the potential pathogenicity in tissues were within normal limits, demonstrating that consumption of normodose and highdose of kefir are safe. In addition, administration of the normodose of kefir reduced cholesterol levels and improved the intestinal mucosa of the rats. These results demonstrate that the consumption of kefir is safe. Importantly, while damages are not seen for the high-dose, the normodose consumption is recommended due to the pronounced beneficial effects, as safety is concerned. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  3. Comparison of the enhancement of plasma glucose levels in type 2 diabetes Otsuka Long-Evans Tokushima Fatty rats by oral administration of sucrose or maple syrup.

    Science.gov (United States)

    Nagai, Noriaki; Ito, Yoshimasa; Taga, Atsushi

    2013-01-01

    Maple syrup is used as a premium natural sweeter, and is known for being good for human health. In the present study, we investigate whether maple syrup is suitable as a sweetener in the management of type 2 diabetes using Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of type 2 diabetes mellitus. OLETF rats develop type 2 diabetes mellitus by 30 weeks of age, and 60-week-old OLETF rats show hyperglycemia and hypoinsulinemia via pancreatic β-cell dysfunction. The administration of sucrose or maple syrup following an OGT test increased plasma glucose (PG) levels in OLETF rats, but the enhancement in PG following the oral administration of maple syrup was lower than in the case of sucrose administration in both 30- and 60-week-old OLETF rats. Although, the insulin levels in 30-week-old OLETF rats also increased following the oral administration of sucrose or maple syrup, no increase in insulin levels was seen in 60-week-old OLETF rats following the oral administration of either sucrose or maple syrup. No significant differences were observed in insulin levels between sucrose- and maple syrup-administered OLETF rats at either 30 or 60 weeks of age. The present study strongly suggests that the maple syrup may have a lower glycemic index than sucrose, which may help in the prevention of type 2 diabetes.

  4. Field trial of GABA-fortified rice plants and oral administration of milled rice in spontaneously hypertensive rats.

    Science.gov (United States)

    Kowaka, Emi; Shimajiri, Yasuka; Kawakami, Kouhei; Tongu, Miki; Akama, Kazuhito

    2015-06-01

    Hypertension is one of the most critical risk factors accompanying cardiovascular diseases. γ-Aminobutyric acid (GABA) is a non-protein amino acid that functions as a major neurotransmitter in mammals and also as a blood-pressure lowering agent. We previously produced GABA-fortified rice lines of a popular Japonica rice cultivar 'Koshihikari' by genetic manipulation of GABA shunt-related genes. In the study reported here, we grew these same novel rice lines in a field trial and administered the milled rice orally to rats. The yield parameters of the transgenic rice plants were almost unchanged compared to those of untransformed cv. 'Koshihikari' plants, while the rice grains of the transgenic plants contained a high GABA content (3.5 g GABA/kg brown rice; 0.75-0.85 GABA g/kg milled rice) in a greenhouse trial. Oral administration of a diet containing 2.5% GABA-fortified rice, with a daily intake for 8 weeks, had an approximately 20 mmHg anti-hypertensive effect in spontaneous hypertensive rats but not in normotensive Wistar-Kyoto rats. These results suggest that GABA-fortified rice may be applicable as a staple food to control or prevent hypertension.

  5. Interaction of titanium dioxide nanoparticles with glucose on young rats after oral administration.

    Science.gov (United States)

    Chen, Zhangjian; Wang, Yun; Zhuo, Lin; Chen, Shi; Zhao, Lin; Chen, Tian; Li, Yang; Zhang, Wenxiao; Gao, Xin; Li, Ping; Wang, Haifang; Jia, Guang

    2015-10-01

    Titanium dioxide nanoparticles (TiO2 NPs) have a broad application prospect in replace with TiO2 used as a food additive, especially used in sweets. Understanding the interaction of TiO2 NPs with sugar is meaningful for health promotion. We used a young animal model to study the toxicological effect of orally administrated TiO2 NPs at doses of 0, 2, 10 and 50 mg/kg per day with or without daily consumption of 1.8 g/kg glucose for 30 days and 90 days. The results showed that oral exposure to TiO2 NPs and TiO2 NPs+glucose both induced liver, kidney, and heart injuries as well as changes in the count of white and red blood cells in a dose, time and gender-dependent manner. The toxicological interactions between orally-administrated TiO2 NPs and glucose were evident, but differed among target organs. These results suggest that it is necessary to limit dietary co-exposure to TiO2 NPs and sugar. Nanotechnology has gained entrance in the food industry, with the presence of nanoparticles now in many food items. Despite this increasing trend, the potential toxic effects of these nanoparticles to human remain unknown. In this article, the authors studied titanium dioxide nanoparticles (TiO2 NPs), which are commonly used as food additive, together with glucose. The findings of possible adverse effects on liver, kidney, and heart might point to a rethink of using glucose and TiO2 NPs combination. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Determination of rhynchophylline and hirsutine in rat plasma by UPLC-MS/MS after oral administration of Uncaria rhynchophylla extract.

    Science.gov (United States)

    Wu, Yu-Tse; Lin, Lie-Chwen; Tsai, Tung-Hu

    2014-03-01

    An ultra-performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS) method was developed and validated to concurrently determine rhynchophylline and hirsutine in rat plasma. The sample preparation of rat plasma was achieved by alkalization and liquid-liquid extraction. The mass transition of precursor ion → product ion pairs were monitored at m/z 385.2 → 160.0 for rhynchophylline, m/z 369.3 → 144.0 for hirsutine and m/z 414.0 → 220.0 for noscapine (internal standard). This method revealed linear relationships from 2.5 to 50 ng/mL (r(2)  > 0.997) for rhynchophylline and from 2.5 to 50 ng/mL (r(2)  > 0.998) for hirsutine. The limit of quantification values for rhynchophylline and hirsutine in rat plasma were both 2.5 ng/mL. Intra-day and inter-day precisions were within 10.6% and 12.5%, respectively, for rhynchophylline and hirsutine, and the accuracy (bias) was 83.6% for rhynchophylline, 73.4% for hirsutine and 90.7% for the internal standard. This method was applied successfully to a pharmacokinetic study of rhynchophylline and hirsutine in rats after oral administration. Copyright © 2013 John Wiley & Sons, Ltd.

  7. [Interaction between fluorine and zinc after long-term oral administration into the digestive system of rats].

    Science.gov (United States)

    Mazurek-Mochol, Małgorzata

    2002-01-01

    Drug interactions are the side effect of administration of two or more drugs or a drug-food combination. Although some drug interactions are intentional and beneficial to the patient, the majority are unintentional and associated with a potentially harmful effect. The aim of this study was to search for interactions in rats between fluoride and zinc administered orally for 12 weeks and to elucidate any potential toxicological and therapeutic consequences. 60 male Wistar rats were divided into six groups of ten rats each and exposed to: 1. controls (distilled water); 2. sodium fluoride (NaF); 3. low-dose zinc (Zn); 4. high-dose zinc; 5. NaF + low-dose Zn; 6. NaF + high-dose Zn. At the end of the experiment the content of F- and Zn+ in serum, urine, incisors, femur and mandible was measured and densitometry of femoral bones was performed. Serum alkaline phosphatase, alanine and aspartate aminotransferase activities, as well as bilirubin and creatinine concentrations were determined to confirm non-toxicity of fluoride dose. Animals receiving NaF only demonstrated higher content of fluorine in serum, urine bones and teeth. Zinc concentrations in serum, urine, bones and teeth were elevated in rats receiving zinc with or without NaF. Fluorine accumulation in bones and teeth was reduced by Zn, but in general the effect lacked statistical significance. Zinc slightly reduced the concentrations of fluorine in serum and urine. Sodium fluoride slightly reduced the concentration of zinc in serum and urine. Bone mineral content (BMC) was significantly increased by NaF and was not further increased by co-administration of zinc. No changes in serum alkaline phosphatase, alanine and aspartate aminotransferase activities, bilirubin and creatinine concentrations were detected. In conclusion, simultaneous administration of fluorine and zinc may be beneficial for prevention and treatment of pathologic conditions in bones and teeth and is not accompanied by an increase in fluorine

  8. Oral Administration of α-Asarone Promotes Functional Recovery in Rats With Spinal Cord Injury

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    Min-Jae Jo

    2018-05-01

    Full Text Available α-asarone, a bioactive compound found in Acorus plant species, has been shown to exhibit neuroprotective, anti-oxidative, anti-inflammatory, and cognitive-enhancing effects. However, the effects of α-asarone on spinal cord injury (SCI have not yet been elucidated. The present study investigated the effects of α-asarone on the mRNA of pro-inflammatory cytokines, macrophage polarization toward an anti-inflammatory M2 phenotype, and angiogenesis in rats with compressive SCI. α-Asarone was orally administered (10 mg/kg once per day for 14 days following moderate static compression SCI. Compared to controls, α-asarone treatment significantly improved locomotor score, prevented neuroinflammation, and facilitated angiogenesis in the spinal cord at 14 days after SCI. Furthermore, α-asarone significantly reduced the TNF-α, IL-1β, IL-6, monocyte chemoattractant protein 1 (MCP-1, macrophage inflammatory protein 2 (MIP-2, and inducible nitric oxide synthase (iNOS levels but increased the IL-4, IL-10, and arginase 1 levels at 24 h after SCI. At 7 and 14 days after SCI, immunohistochemistry showed reduced reactive gliosis and neuroinflammation and an increased expression of M2 macrophage markers and angiogenesis. The results suggest that the inhibition of pro-inflammatory cytokines, macrophage polarization toward an anti-inflammatory M2 phenotype, and angiogenesis by α-asarone may be some of the mechanisms underlying the α-asarone-mediated neuroprotective effects on an injured spinal cord.

  9. Changes in Bioavailability of Omega-3 (DHA through Alpha-Tocopheryl Phosphate Mixture (TPM after Oral Administration in Rats

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    Roksan Libinaki

    2017-09-01

    Full Text Available Benefits of Omega-3 Docosahexaenoic acid (DHA supplements are hindered by their poor solubility and bioavailability. This study investigated the bioavailability of various formulations of Omega-3 and tocopheryl phosphate mixture (TPM, following oral administration in rats, and assessed whether TPM could improve the oral absorption of DHA. The rats were administered with a high (265.7 mg/kg or low dose (88.6 mg/kg of DHA. TPM was examined at 1:0.1 w/w (low TPM dose and 1:0.5 w/w (high TPM dose. Over 24 h, the DHA plasma concentration followed a TPM dose-dependent relationship, reflected in the higher mean Cmax values (78.39 and 91.95 μg/mL and AUC values (1396.60 and 1560.60 for the low and high TPM, respectively. The biggest difference between the low dose DHA control (LDCont and TPM formulations was at 4 h after supplementation, where the low and high TPM showed a mean 20% (ns and 50% (p < 0.05 increase in DHA plasma concentrations versus the control formulation. After correcting for baseline endogenous DHA, the mean plasma DHA at 4 h produced by the LD-HTPM was nearly double (90% the LDC control (p = 0.057. This study demonstrated that co-administering omega-3 with TPM significantly increases the bioavailability of DHA in the plasma, suggesting potential use for commercially available TPM + DHA fortified products.

  10. The combined effect of laser and oral administration of Iranian propolis extract on skin wound healing in male rats

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    Nematollah Ghaibi

    2015-05-01

    Full Text Available Background: To date, a lot of research has been carried out on the effect of medications and surgical methods on the treatment of wounds, but no ideal achievement has been obtained yet. This study was conducted to investigate the single and combined effect of laser and propolis on skin wound healing in male rats. Methods: 40 Wistar male rats (200-250 g were divided into 4 groups (n= 10. All animals were anesthetized and sterile skin wound was created by surgical scissors. Control group had no treatment, the second group was treated with laser (10 mW, the third group was treated with oral propolis (100 mg /kg; 3 times /day and the forth group was treated with both laser and propolis. The wound healing level was measured based on the wound area and urinary hydroxyproline content. Results: Urinary hydroxyproline content was increased in groups treated with laser, propolis and combined laser and propolis compared to the control group (P<0.01, 0.05 and 0.01, respectively. Also at the end of the treatment period, the wound extent was significantly lower in the laser, propolis, and combined laser and propolis groups than the control (P<0.05, 0.05 and 0.01, respectively. There was no significant difference between treatment groups. Conclusion: Our results showed that oral administration of propolis or low power laser radiation can increase the wound healing rate.

  11. Disposition and metabolism of glyphosate in the Sprague Dawley rat following oral administration

    International Nuclear Information System (INIS)

    Brewster, D.W.; Warren, J.A.; Hopkins, W.E.

    1991-01-01

    Five groups of male SD rats were administered 14 C-labelled glyphosate, (N-[(phosphonomethyl)glycine]) by gavage at a dose level of 10 mg/kg. Animals were killed 2, 6.3, 28, 96 and 168 hours after dosing and the amount of glyphosate-derived material in various organs and excreta were determined. In addition, the metabolic profile in tissues containing > 1% of the administered dose was evaluated. Approximately 93% of the body burden 2 hours after administration was associated with the GI contents and small intestinal tissue. The total body burden 7 days after administration was ∼1% of the dose. Only the kidneys, small intestine, colon, bone, GI contents, residual carcass contained > 1% of the dose 6 hours after administration and the metabolic profiles of these tissues indicated that ∼100% of the body burden was present as unmetabolized parent material. Glyphosate was rapidly eliminated from these tissues with halflives ranging from 20 to 90 hours. A minor metabolite comprising < 0.1% of the dose was detected in the GI contents and colon tissue of 3 animals. Less than 40% of the administered dose was absorbed from the gut and glyphosate was rapidly eliminated from the body with urine and feces being equally important routes of elimination. The whole body halflife was approximately 52 hours. The results from this study indicate that no toxic metabolites of glyphosate were produced, as there was little evidence of metabolism, and essentially 100% of the body burden was parent glyphosate with no significant persistence of accumulated material

  12. Oral administration of Moringa oleifera oil but not coconut oil prevents mercury-induced testicular toxicity in rats.

    Science.gov (United States)

    Abarikwu, S O; Benjamin, S; Ebah, S G; Obilor, G; Agbam, G

    2017-02-01

    This study was conducted to compare the effects of administration of coconut oil (CO) and Moringa oleifera oil (MO) on testicular oxidative stress, sperm quality and steroidogenesis parameters in rats treated with mercury chloride (HgCl 2 ). After 15 days of oral administration of CO (2 ml kg -1 body weight) and MO (2 ml kg -1 body weight) along with intraperitoneal (i.p.) administration of HgCl 2 (5 mg kg -1 body weight) alone or in combination, we found that CO treatment did not protect against HgCl 2 -induced poor sperm quality (motility, count) as well as decreased testosterone level and 17β-hydroxysteroid dehydrogenase (17β-HSD) activity. Treatment with CO alone decreased glutathione (GSH), and glutathione peroxidase (GSH-Px) activities and increased malondialdehyde (MDA) level in rat's testis, whereas MO did not change these parameters. Cotreatment with MO prevented HgCl 2 -induced testicular catalase (CAT) and superoxide dismutase (SOD) activities, poor sperm quality and low testosterone level and also blocks the adverse effect of CO+HgCl 2 (2 ml kg -1 body weight + 5 mg kg -1 body weight) on the investigated endpoints. In conclusion, MO and not CO decreased the deleterious effects of HgCl 2 on sperm quality and steroidogenesis in rats and also strengthen the antioxidant defence of the testes. Therefore, MO is beneficial as an antioxidant in HgCl 2 -induced oxidative damage. © 2016 Blackwell Verlag GmbH.

  13. Longer period of oral administration of aspartame on cytokine response in Wistar albino rats.

    Science.gov (United States)

    Choudhary, Arbind Kumar; Sheela Devi, Rathinasamy

    2015-03-01

    Aspartame is a non-nutritive sweetener particularly used in 'diet' and 'low calorie' products and also in a variety of foods, drugs and hygiene products. Aspartame is metabolized by gut esterases and peptidases to three common chemicals: the amino acids, aspartic acid and phenylalanine, and small amounts of methanol. The aim of the present study was to assess potential changes in molecular mediators of aspartame as a chemical stressor in rats. The effects of long-term administration of aspartame (40 mg/kg body weight/day) were tested in Wistar Albino rats. The treatment effects were assessed in different conditions, including control groups. After 90 days of treatment, circulating concentrations of different parameters were assessed: corticosterone, lipid peroxidation, antioxidant activity, nitric oxide, reduced glutathione and cytokines (interleukin 2, interleukin 4, tumor necrosis factor-α and interferon-γ). The results show that there was a significant increase in plasma corticosterone, serum lipid peroxidation and nitric oxide level along with a decrease in enzymatic and non-enzymatic antioxidant as well as significant decrease in interleukin 2, tumor necrosis factor-α and interferon-γ. There was also a significant increase in interleukin 4 irrespective of whether the animals were immunized or not. The findings clearly point out that aspartame acts as a chemical stressor because of increased corticosterone level and increased lipid peroxidation and nitric oxide level induce generation of free radicals in serum which may be the reason for variation of cytokine level and finally results in alteration of immune function. Aspartame metabolite methanol or formaldehyde may be the causative factors behind the changes observed. Copyright © 2014 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

  14. Experimental oral iron administration: Histological investigations and expressions of iron handling proteins in rat retina with aging.

    Science.gov (United States)

    Kumar, Pankaj; Nag, Tapas Chandra; Jha, Kumar Abhiram; Dey, Sanjay Kumar; Kathpalia, Poorti; Maurya, Meenakshi; Gupta, Chandan Lal; Bhatia, Jagriti; Roy, Tara Sankar; Wadhwa, Shashi

    2017-12-01

    Iron is implicated in age-related macular degeneration (AMD). The aim of this study was to see if long-term, experimental iron administration with aging modifies retinal and choroidal structures and expressions of iron handling proteins, to understand some aspects of iron homeostasis. Male Wistar rats were fed with ferrous sulphate heptahydrate (500mg/kg body weight/week, oral; elemental iron availability: 20%) from 2 months of age onward until they were 19.5 month-old. At 8, 14 and 20 months of age, they were sacrificed and serum and retinal iron levels were detected by HPLC. Oxidative stress was analyzed by TBARS method. The retinas were examined for cell death (TUNEL), histology (electron microscopy) and the expressions of transferrin, transferrin receptor-1 [TFR-1], H- and L-ferritin. In control animals, at any age, there was no difference in the serum and retinal iron levels, but the latter increased significantly in 14- and 20 month-old iron-fed rats, indicating that retinal iron accumulation proceeds with progression of aging (>14 months). The serum and retinal TBARS levels increased significantly with progression of aging in experimental but not in control rats. There was significant damage to choriocapillaris, accumulation of phagosomes in retinal pigment epithelium and increased incidence of TUNEL+ cells in outer nuclear layer and vacuolation in inner nuclear layer (INL) of 20 month-aged experimental rats, compared to those in age-matched controls. Vacuolations in INL could indicate a long-term effect of iron accumulation in the inner retina. These events paralleled the increased expression of ferritins and transferrin and a decrease in the expression of TFR-1 in iron-fed rats with aging, thereby maintaining iron homeostasis in the retina. As some of these changes mimic with those happening in eyes with AMD, this model can be utilized to understand iron-induced pathophysiological changes in AMD. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Beneficial Effects of Long-Term Administration of an Oral Formulation of Angiotensin-(1–7 in Infarcted Rats

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    Fúlvia D. Marques

    2012-01-01

    Full Text Available In this study was evaluated the chronic cardiac effects of a formulation developed by including angiotensin(Ang-(1–7 in hydroxypropyl β-cyclodextrin (HPβCD, in infarcted rats. Myocardial infarction (MI was induced by left coronary artery occlusion. HPβCD/Ang-(1–7 was administered for 60 days (76 μg/Kg/once a day/gavage starting immediately before infarction. Echocardiography was utilized to evaluate usual cardiac parameters, and radial strain method was used to analyze the velocity and displacement of myocardial fibers at initial time and 15, 30, and 50 days after surgery. Real-time PCR was utilized to evaluate the fibrotic signaling involved in the remodeling process. Once-a-day oral HPβCD/Ang-(1–7 administration improved the cardiac function and reduced the deleterious effects induced by MI on TGF-β and collagen type I expression, as well as on the velocity and displacement of myocardial fibers. These findings confirm cardioprotective effects of Ang-(1–7 and indicate HPβCD/Ang-(1–7 as a feasible formulation for long-term oral administration of this heptapeptide.

  16. Pharmacokinetics and dosimetry of the antiandrogen vinclozolin after oral administration in the rat.

    Science.gov (United States)

    Sierra-Santoyo, Adolfo; Castañeda-Hernández, Gilberto; Harrison, Randy A; Barton, Hugh A; Hughes, Michael F

    2008-11-01

    Vinclozolin (V) is a fungicide with antiandrogenic properties. To determine the pharmacokinetics and dosimetry of V, adult male rats were administered an oral dose of V (100 mg/kg) in corn oil and sacrificed over time after dosing. V and its metabolites were analyzed in serum and tissues by high performance liquid chromatography/diode array detector/mass spectrometer. V, 2-[[(3,5-dichlorophenyl)-carbamoyl]oxy]-2-methyl-3-butenoic acid (M1), and 3',5'-dichloro-2-hydroxy-2-methylbut-3-enanilide (M2), and five other metabolites were detected in serum and tissues. One metabolite was identified as 3',5'-dichloro-2,3,4-trihydroxy-2-methylbutylanilide (M5). The mean serum concentration data for V were fitted to a one-compartment model for kinetic analysis. At 2 h, V serum concentration peaked; whereas only trace levels were detected at 24 h (t(1/2 elim) = 3.6 h). V was detected in all tissues and preferentially accumulated in fat. M1 serum levels increased until 8 h, being at least 2-fold higher than those of V at this time, and then declined with a t(1/2) = 3.3 h. M5 was the main metabolite in serum and tissues. Serum M5 levels were 5-fold higher than V and 2-fold greater than M1 at all times. At 48 h, M5 remained the main metabolite (t(1/2 elim) = 13.1 h). Liver and kidney exhibited the highest levels of M5, V, and M1. M2 and 3,5-dichloroaniline had the lowest levels of V metabolites in serum and tissues. V is well absorbed, extensively metabolized and widely distributed. M5, the most abundant V metabolite, may be used as an exposure biomarker for pharmacokinetic modeling. These results may clarify the relationship between toxicity and tissue dose of V and its metabolites.

  17. Improved Safety, Bioavailability and Pharmacokinetics of Zidovudine through Lactoferrin Nanoparticles during Oral Administration in Rats.

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    Prashant Kumar

    Full Text Available Zidovudine (AZT is one of the most referred antiretroviral drug. In spite of its higher bioavailability (50-75% the most important reason of its cessation are bone marrow suppression, anemia, neutropenia and various organs related toxicities. This study aims at the improvement of oral delivery of AZT through its encapsulation in lactoferrin nanoparticles (AZT-lactonano. The nanoparticles (NPs are of 50-60 nm in size and exhibit 67% encapsulation of the AZT. They are stable in simulated gastric and intestinal fluids. Anti-HIV-1 activity of AZT remains unaltered in nanoformulation in acute infection. The bioavailability and tissue distribution of AZT is higher in blood followed by liver and kidney. AZT-lactonano causes the improvement of pharmacokinetic profile as compared to soluble AZT; a more than 4 fold increase in AUC and AUMC in male and female rats. The serum Cmax for AZT-lactonano was increased by 30%. Similarly there was nearly 2-fold increase in Tmax and t1/2. Our in vitro study confirms that, the endosomal pH is ideal for drug release from NPs and shows constant release from up to 96h. Bone marrow micronucleus assay show that nanoformulation exhibits approximately 2fold lower toxicity than soluble form. Histopathological and biochemical analysis further confirms that less or no significant organ toxicities when nanoparticles were used. AZT-lactonano has shown its higher efficacy, low organs related toxicities, improved pharmacokinetics parameter while keeping the antiviral activity intact. Thus, the nanoformulation are safe for the target specific drug delivery.

  18. Pharmacokinetic Comparison of Berberine in Rat Plasma after Oral Administration of Berberine Hydrochloride in Normal and Post Inflammation Irritable Bowel Syndrome Rats

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    Zipeng Gong

    2014-01-01

    Full Text Available In the present study, post inflammation irritable bowel syndrome (PI-IBS rats were firstly established by intracolonic instillation of acetic acid with restraint stress. Then the pharmacokinetics of berberine in the rat plasma were compared after oral administration of berberine hydrochloride (25 mg/kg to normal rats and PI-IBS rats. Quantification of berberine in the rat plasma was achieved by using a sensitive and rapid UPLC-MS/MS method. Plasma samples were collected at 15 different points in time and the pharmacokinetic parameters were analyzed by WinNonlin software. Compared with the normal group, area under the plasma concentration vs. time curve from zero to last sampling time (AUC0–t and total body clearance (CL/F in the model group significantly increased or decreased, (2039.49 ± 492.24 vs. 2763.43 ± 203.14; 4999.34 ± 1198.79 vs. 3270.57 ± 58.32 respectively. The results indicated that the pharmacokinetic process of berberine could be altered in PI-IBS pathological conditions.

  19. Evaluation of the radioprotective Effect of the co-oral Administration of Vitamin B12 with Vitamin c on some Haematological and Biochemical Alterations in Male Albino Rats

    International Nuclear Information System (INIS)

    Abdel-Magied, N.

    2013-01-01

    The objective of this study was to evaluate the prophylactic efficacy of co-oral administration of vitamin B 12 with vitamin C against radiation induced haematological and biochemical alterations in male albino rats. Male albino rats were divided into six groups (n=8). Group 1: rats were kept as control, Group 2; rats received orally vita-min B 12 (2000μgkg -1 ). Group 3; rats received Vitamin B 12 with Vitamin C (500mgkg -1 ). Group 4; rats whole body exposed to 7Gy of gamma rays. Group 5; rats received vitamin B 12 for 21 successive days before irradiation. Group 6; rats received Vitamin B 12 with Vitamin C for 21 successive days before irradiation. Animals were sacrificed the third day post irradiation. The oral administration of Vitamin B 12 with or with-out Vitamin C enhanced the recovery from radiation-induced haemopoietic injury and some biochemical changes demonstrated by a significant increase (p0.05>) of WBCs, RBCs and Platelets count, Hb content, Hct%, serum erythropoietin and iron levels and a significant reduction (p0.05>) of serum homocysteine level (Hcy), creatine kinase (CK-MB) and lactate dehydrogenase (LDH) activities compared to their respective values in irradiated rats. Improvement of oxidative stress in heart and spleen tissues denoted by a significant decrease in lipid peroxidation (MDA) and a significant increase in glutathione (GSH) content was recorded also. The co-oral administration of vitamin B 12 with vitamin C has no effect on the prophylactic efficacy of vitamin B 12

  20. Oral administration of eicosapentaenoic acid or docosahexaenoic acid modifies cardiac function and ameliorates congestive heart failure in male rats.

    Science.gov (United States)

    Yamanushi, Tomoko T; Kabuto, Hideaki; Hirakawa, Eiichiro; Janjua, Najma; Takayama, Fusako; Mankura, Mitsumasa

    2014-04-01

    This study assessed the effects of eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) on normal cardiac function (part 1) and congestive heart failure (CHF) (part 2) through electrocardiogram analysis and determination of EPA, DHA, and arachidonic acid (AA) concentrations in rat hearts. In part 2, pathologic assessments were also performed. For part 1 of this study, 4-wk-old male rats were divided into a control group and 2 experimental groups. The rats daily were orally administered (1 g/kg body weight) saline, EPA-ethyl ester (EPA-Et; E group), or DHA-ethyl ester (DHA-Et; D group), respectively, for 28 d. ECGs revealed that QT intervals were significantly shorter for groups E and D compared with the control group (P ≤ 0.05). Relative to the control group, the concentration of EPA was higher in the E group and concentrations of EPA and DHA were higher in the D group, although AA concentrations were lower (P ≤ 0.05). In part 2, CHF was produced by subcutaneous injection of monocrotaline into 5-wk-old rats. At 3 d before monocrotaline injection, rats were administered either saline, EPA-Et, or DHA-Et as mentioned above and then killed at 21 d. The study groups were as follows: normal + saline (control), CHF + saline (H group), CHF + EPA-Et (HE group), and CHF + DHA-Et (HD group). QT intervals were significantly shorter (P ≤ 0.05) in the control and HD groups compared with the H and HE groups. Relative to the H group, concentrations of EPA were higher in the HE group and those of DHA were higher in the control and HD groups (P ≤ 0.05). There was less mononuclear cell infiltration in the myocytes of the HD group than in the H group (P = 0.06). The right ventricles in the H, HE, and HD groups showed significantly increased weights (P ≤ 0.05) compared with controls. The administration of EPA-Et or DHA-Et may affect cardiac function by modification of heart fatty acid composition, and the administration of DHA-Et may ameliorate CHF.

  1. Pharmacokinetic-Pharmacodynamic Analysis on Inflammation Rat Model after Oral Administration of Huang Lian Jie Du Decoction.

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    Wei Ren

    Full Text Available Huang-Lian-Jie-Du Decoction (HLJDD is a classical Traditional Chinese Medicine (TCM formula with heat-dissipating and detoxifying effects. It is used to treat inflammation-associated diseases. However, no systematic pharmacokinetic (PK and pharmacodynamic (PD data concerning the activity of HLJDD under inflammatory conditions is available to date. In the present study, the concentration-time profiles and the hepatic clearance rates (HCR of 41 major components in rat plasma in response to the oral administration of a clinical dose of HLJDD were investigated by LC-QqQ-MS using a dynamic multiple reaction monitoring (DMRM method. Additionally, the levels of 7 cytokines (CKs in the plasma and the body temperature of rats were analyzed. Furthermore, a PK-PD model was established to describe the time course of the hemodynamic and anti-inflammatory effects of HLJDD. As one of the three major active constituents in HLJDD, iridoids were absorbed and eliminated more easily and quickly than alkaloids and flavonoids. Compared with the normal controls, the flavonoids, alkaloids and iridoids in inflamed rats exhibited consistently changing trends of PK behaviors, such as higher bioavailability, slower elimination, delays in reaching the maximum concentration (Tmax and longer substantivity. The HCR of iridoids was different from that of alkaloids and flavonoids in inflamed rats. Furthermore, excellent pharmacodynamic effects of HLJDD were observed in inflamed rats. The levels of tumor necrosis factor-α (TNF-α, interleukin-6 (IL-6, IL-1β, IL-10, and macrophage inflammatory protein-2 (MIP-2 and body temperature significantly decreased after the administration of HLJDD. Based on PK-PD modeling with the three-phase synchronous characterization of time-concentration-effect, flavonoids exhibited one mechanism of action in the anti-inflammatory process, while iridoids and alkaloids showed another mechanism of action. Taken together, the results demonstrated that

  2. Comparative pharmacokinetic and tissue distribution profiles of four major bioactive components in normal and hepatic fibrosis rats after oral administration of Fuzheng Huayu recipe.

    Science.gov (United States)

    Yang, Tao; Liu, Shan; Wang, Chang-Hong; Tao, Yan-Yan; Zhou, Hua; Liu, Cheng-Hai

    2015-10-10

    Fuzheng Huayu recipe (FZHY) is a herbal product for the treatment of liver fibrosis approved by the Chinese State Food and Drug Administration (SFDA), but its pharmacokinetics and tissue distribution had not been investigated. In this study, the liver fibrotic model was induced with intraperitoneal injection of dimethylnitrosamine (DMN), and FZHY was given orally to the model and normal rats. The plasma pharmacokinetics and tissue distribution profiles of four major bioactive components from FZHY were analyzed in the normal and fibrotic rat groups using an ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method. Results revealed that the bioavailabilities of danshensu (DSS), salvianolic acid B (SAB) and rosmarinic acid (ROS) in liver fibrotic rats increased 1.49, 3.31 and 2.37-fold, respectively, compared to normal rats. There was no obvious difference in the pharmacokinetics of amygdalin (AMY) between the normal and fibrotic rats. The tissue distribution of DSS, SAB, and AMY trended to be mostly in the kidney and lung. The distribution of DSS, SAB, and AMY in liver tissue of the model rats was significantly decreased compared to the normal rats. Significant differences in the pharmacokinetics and tissue distribution profiles of DSS, ROS, SAB and AMY were observed in rats with hepatic fibrosis after oral administration of FZHY. These results provide a meaningful basis for developing a clinical dosage regimen in the treatment of hepatic fibrosis by FZHY. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Oral administration of kaempferol inhibits bone loss in rat model of ovariectomy-induced osteopenia.

    Science.gov (United States)

    Nowak, Beata; Matuszewska, Agnieszka; Nikodem, Anna; Filipiak, Jarosław; Landwójtowicz, Marcin; Sadanowicz, Ewa; Jędrzejuk, Diana; Rzeszutko, Marta; Zduniak, Krzysztof; Piasecki, Tomasz; Kowalski, Przemysław; Dziewiszek, Wojciech; Merwid-Ląd, Anna; Trocha, Małgorzata; Sozański, Tomasz; Kwiatkowska, Joanna; Bolanowski, Marek; Szeląg, Adam

    2017-10-01

    Postmenopausal osteoporosis and osteoporotic fractures constitute an increasing problem in developing countries. Kaempferol, isolated from seeds of Cuscuta chinensis, is an active flavonoid inhibiting in vitro osteoclast activity. The aim of the presented research was an assessment of kaempferol effect on estrogen-deficiency-induced bone structure disturbances in rats. The study was performed on 24 Wistar female rats divided into 3 groups: SHAM - rats undergoing a "sham" surgery, OVX-C - control group of animals that underwent ovariectomy, OVX-K - rats undergoing ovariectomy and receiving kaempferol for 8 weeks (from day 56 to day 112). In the OVX-K group, contrary to the OVX-C one, there was no significant decrease in femoral bone mineral density (BMD). A significant increase in Young's modulus was observed in the OVX-K group compared to the OVX-C (15.33±2.51GPa vs. 11.14±1.93GPa, p<0.05). A decreased bone turnover was detected in the OVX-K group. Tissue volume ratio (BV/TV) and trabecular bone perimeter were increased in the OVX-K group compared to the OVX-C one (0.241±0.037 vs. 0.170±0.022, p<0.05 and 15.52±2.78mm vs. 9.67±3.07mm, p<0.05, respectively). Kaempferol has a beneficial influence on estrogen-deficiency-induced disturbances of bone structure in rats. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  4. Pharmacokinetic Comparative Study of Gastrodin and Rhynchophylline after Oral Administration of Different Prescriptions of Yizhi Tablets in Rats by an HPLC-ESI/MS Method

    Science.gov (United States)

    Ge, Zhaohui; Liang, Qionglin; Wang, Yiming; Luo, Guoan

    2014-01-01

    Pharmacokinetic characters of rhynchophylline (RIN), gastrodin (GAS), and gastrodigenin (p-hydroxybenzyl alcohol, HBA) were investigated after oral administration of different prescriptions of Yizhi: Yizhi tablets or effective parts of tianma (total saponins from Gastrodiae, EPT) and gouteng (rhynchophylla alkaloids, EPG). At different predetermined time points after administration, the concentrations of GAS, HBA, and RIN in rat plasma were determined by an HPLC-ESI/MS method, and the main pharmacokinetic parameters were investigated. The results showed that the pharmacokinetic parameters C max and AUC0–∞ (P < 0.05) were dramatically different after oral administration of different prescriptions of Yizhi. The data indicated that the pharmacokinetic processes of GAS, HBA, and RIN in rats would interact with each other or be affected by other components in Yizhi. The rationality of the compatibility of Uncaria and Gastrodia elata as a classic “herb pair” has been verified from the pharmacokinetic viewpoint. PMID:25610474

  5. Pharmacokinetic Comparative Study of Gastrodin and Rhynchophylline after Oral Administration of Different Prescriptions of Yizhi Tablets in Rats by an HPLC-ESI/MS Method

    Directory of Open Access Journals (Sweden)

    Zhaohui Ge

    2014-01-01

    Full Text Available Pharmacokinetic characters of rhynchophylline (RIN, gastrodin (GAS, and gastrodigenin (p-hydroxybenzyl alcohol, HBA were investigated after oral administration of different prescriptions of Yizhi: Yizhi tablets or effective parts of tianma (total saponins from Gastrodiae, EPT and gouteng (rhynchophylla alkaloids, EPG. At different predetermined time points after administration, the concentrations of GAS, HBA, and RIN in rat plasma were determined by an HPLC-ESI/MS method, and the main pharmacokinetic parameters were investigated. The results showed that the pharmacokinetic parameters Cmax and Cmax⁡ and AUC0–∞ (P<0.05 were dramatically different after oral administration of different prescriptions of Yizhi. The data indicated that the pharmacokinetic processes of GAS, HBA, and RIN in rats would interact with each other or be affected by other components in Yizhi. The rationality of the compatibility of Uncaria and Gastrodia elata as a classic “herb pair” has been verified from the pharmacokinetic viewpoint.

  6. Effects of oral, subchronic cadmium administration on fertility prenatal and postnatal progeny development in rats

    Energy Technology Data Exchange (ETDEWEB)

    Baranski, B.; Stetkiewicz, I.; Sitarek, K.; Szymczak, W.

    1983-12-01

    Cadmium chloride was administered by gavage to female rats 5 days a week for 5 weeks, then during mating and gestation periods at doses of 0.04, 0.4, and 4 mg Cd/kg/day. Treatment with cadmium neither affected the survival and fertility of females, nor produced overt fetotoxic effects. Fetal cadmium concentration was not related to the level of exposure. Litter size, body weight gain and viability of offspring during 2 months after parturition were similar in all groups. The exploratory locomotor activity of 2-month-old males and females born to rats given 0.4 and 4 mg Cd/kg/day was significantly reduced. The progeny of cadmium-treated females showed decreased performance in the rotarod test. In general, the degree of behavioral impairment was dose-related.

  7. Stress, Predictability, and Oral Fentanyl Self-Administration in Female and Male Rats

    Science.gov (United States)

    1995-03-09

    naloxone. When dissolved in water, fentanyl hydrochloride (Hel) is less bitter-tasting than morphine and it is readily self- administered by rats...and for assessment of the biochemical effects of the stressor. Drugs Fentanyl- hydrochloride (HCI) (NIDA, Baltimore, MD), in a concentration of 50...responses despite lower opioid SA, treatment for men might focus on pharmacologic replacement therapies, such as methadone maintenance programs. The

  8. Oral administration of leaf extracts of Momordica charantia affect reproductive hormones of adult female Wistar rats

    Science.gov (United States)

    Adewale, Osonuga Odusoga; Oduyemi, Osonuga Ifabunmi; Ayokunle, Osonuga

    2014-01-01

    Objective To determine the effect of graded doses of aqueous leaf extracts of Momordica charantia on fertility hormones of female albino rats. Methods Twenty adult, healthy, female Wistar rats were divided into four groups: low dose (LD), moderate dose (MD) and high dose (HD) groups which received 12.5 g, 25.0 g, 50.0 g of the leaf extract respectively and control group that was given with water ad libatum. Result Estrogen levels reduced by 6.40 nmol/L, 10.80 nmol/L and 28.00 nmol/L in the LD, MD and HD groups respectively while plasma progesterone of rats in the LD, MD and HD groups reduced by 24.20 nmol/L, 40.8 nmol/L and 59.20 nmol/L respectively. Conclusion Our study has shown that the antifertility effect of Momordica charantia is achieved in a dose dependent manner. Hence, cautious use of such medication should be advocated especially when managing couples for infertility. PMID:25183143

  9. Biochemical properties of the plasma of rats with the experimentally induced hepatitis after oral administration of sodium diclofenac

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    V. Gryshchenko

    2017-04-01

    Full Text Available We conducted an analysis of the metabolic activity of the liver and defined the peculiarities of biochemical parameters and macroelement composition of blood plasma of rats with experimentally induced toxic hepatitis. Hepatopathology was modeled by oral administration of sodium diclofenac at a dose of 12.5 mg/kg of body mass to rats during 14 days. For the preparation of plasma, rat blood was collected from the abdominal aorta into test-tubes with heparin, and then it was centrifuged at 1500 rev./min for 15–20 min. Then we studied biochemical parameters of blood indicators (level of total protein, albumin, total and conjugated bilirubin, glucose, creatinine, urea, triacylglycerols, cholesterol, thymol test value, activities of ALT, AST, LP and GGT, amylase and lipase and also its macroelement composition: concentration of sodium, potassium, phosphorus, calcium, magnesium and chlorine using automatic biochemical analyzer «BioSystem A15» (Spain according to the recommendations of the International Federation of Clinical Chemistry (IFCC Experts Panel. The results of the introduction in the laboratory rats of drug-induced toxic hepatitis indicate a decrease of metabolic activity of hepatocytes under this hepatopathology. The results showed a decrease in total protein by 17%, albumin by 11%, glucose by 6% , triacylglycerols by 53%, cholesterol by 54%, and an appreciable increase in thymol test value (by a factor of 2.8. Besides this, disruption of the liver pigment function, development of cytolytic syndrome and intrahepatic cholestasis were revealed in the affected animals. The increased activity of the studied blood enzymes (ALT by 28%, AST by 45%, LP by 30%, GGT by a factor of 2.1 confirmed these disruptions. The increase in AST/ALT by 12% ratio confirmed destructive changes in cell membranes, including mitochondrial membranes, caused by metabolic changes under the toxic influence of sodium diclofenac. The increased activities of α-amylase by

  10. Oral administration of curcumin (Curcuma longa) can attenuate the neutrophil inflammatory response in zymosan-induced arthritis in rats.

    Science.gov (United States)

    Nonose, Nilson; Pereira, José Aires; Machado, Paulo Roberto Moura; Rodrigues, Murilo Rocha; Sato, Daniela Tiemi; Martinez, Carlos Augusto Real

    2014-11-01

    To evaluate the effect of curcumin in the acute phase of zymosan-induced arthritis. Twenty-eight male rats were subjected to intra-articular infiltration of zymosan of both knees and, in four the infiltration was made with saline. The animals were divided into five groups second received every six hours by gavage: corn oil by (positive and negative control); curcumin (100 mg/kg); prednisone 1 mg/kg/day; prednisone 8 mg/kg. All animals were sacrificed after six, 12, 24 and 48 hours of the infiltration. The knees were removed for evaluation of neutrophil infiltration. The number of neutrophils was counted by computer-assisted analysis of the images. The neutrophil infiltrate was stratified into four grades: 0 = normal; + = mild; ++/+++ = moderate; > ++++ = severe. The results were compared using the Mann-Whitney test and the variance by Kruskal-Wallis test adopting a significance level of 5% (pCurcumin reduces inflammatory activity in the first six hours after zymosan-induced arthritis when compared to saline (pCurcumin was more effective than lower doses of prednisone in the first six hours after induction of the arthritis. After 12, 24 and 48 hours, curcumin does not have the same anti-inflammatory effects when compared to prednisone. After 48 hours, prednisone is more effective than curcumin in reducing the inflammatory infiltrate regardless of the dose of prednisone used. Oral administration of curcumin reduces inflammation in the first six hours after experimentally zymosan-induced arthritis.

  11. Comparative Pharmacokinetics of Chlorpyrifos versus its Major Metabolites Following Oral Administration in the Rat

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    Busby-Hjerpe, Andrea L.; Campbell, James A.; Smith, Jordan N.; Lee, Sookwang; Poet, Torka S.; Barr, Dana; Timchalk, Charles

    2010-01-31

    Chlorpyrifos (CPF) is a commonly used diethylphosphorothionate organophosphorus (OP) insecticide. Diethylphosphate (DEP), diethylthiophosphate (DETP) and 3,5,6-trichloro-2-pyridinol (TCPy) are products of in vivo metabolism and environmental degradation of CPF and are routinely measured in urine as biomarkers of exposure. Hence, urinary biomonitoring of TCPy, DEP and DETP may be reflective of an individual’s contact with both the parent pesticide and exposure to these metabolites. In the current study, simultaneous dosing of 13C- or 2H- isotopically labeled CPF (13Clabeled CPF, 5 13C on the TCPy ring; or 2H-labeled CPF, diethyl-D10 (deuterium labeled) on the side chain) were exploited to directly compare the pharmacokinetics and metabolism of CPF with TCPy, and DETP. Individual metabolites were co-administered (oral gavage) with the parent compound at equal molar doses (14 μmol/kg; ~5mg/kg CPF). The key objective in the current study was to quantitatively evaluate the pharmacokinetics of the individual metabolites relative to their formation following a dose of CPF. Major differences in the pharmacokinetics between CPF and metabolites doses were observed within the first 3 h of exposure, due to the required metabolism of CPF to initially form TCPy and DETP. Nonetheless, once a substantial amount of CPF has been metabolized (≥ 3 h post-dosing) pharmacokinetics for both treatment groups and metabolites were very comparable. Urinary excretion rates for orally administered TCPy and DETP relative to 13C-CPF or 2H-CPF derived 13C-TCPy and 2H-DETP were consistent with blood pharmacokinetics, and the urinary clearance of metabolite dosed groups were comparable with the results for the 13C- and 2H-CPF groups. Since the pharmacokinetics of the individual metabolites were not modified by co-exposure to 3 CPF; it suggests that environmental exposure to low dose mixtures of pesticides and metabolites will not impact the pharmacokinetics of either.

  12. LC determination and pharmacokinetic study of the main phenolic components of Portulaca oleracea L. extract in rat plasma after oral administration.

    Science.gov (United States)

    Cheng, Zhongzhe; Wang, Dong; Zhang, Wenjie; Du, Yang; Wang, Yunjiao; Zhai, Yanjun; Ying, Xixiang; Kang, Tingguo

    2012-01-01

    This study investigated the pharmacokinetics of hesperidin (HP), ferulic acid (FA) and p-coumaric acid (CA) in rat plasma after oral administration of Portulaca oleracea L. extract (POE). The plasma concentrations were determined by HPLC with vitexin-2″-O-rhamnoside (VR) as internal standard. The calibration curves were linear over the range 0.1-5 µg mL(-1), 0.1-5 µg mL(-1)and 0.015-3 µg mL(-1) for HP, FA and CA, respectively. The validated method was suitable to the pharmacokinetic study of HP, FA and CA in rats after oral administration at a single dose of POE.

  13. Oral Administration of (S)-Allyl-l-Cysteine and Aged Garlic Extract to Rats: Determination of Metabolites and Their Pharmacokinetics.

    Science.gov (United States)

    Park, Taehoon; Oh, Ju-Hee; Lee, Joo Hyun; Park, Sang Cheol; Jang, Young Pyo; Lee, Young-Joo

    2017-11-01

    ( S )-Allyl-l-cysteine is the major bioactive compound in garlic. ( S )-Allyl-l-cysteine is metabolized to ( S )-allyl-l-cysteine sulfoxide, N -acetyl-( S )-allyl-l-cysteine, and N -acetyl-( S )-allyl-l-cysteine sulfoxide after oral administration. An accurate LC-MS/MS method was developed and validated for the simultaneous quantification of ( S )-allyl-l-cysteine and its metabolites in rat plasma, and the feasibility of using it in pharmacokinetic studies was tested. The analytes were quantified by multiple reaction monitoring using an atmospheric pressure ionization mass spectrometer. Because significant quantitative interference was observed between ( S )-allyl-l-cysteine and N -acetyl-( S )-allyl-l-cysteine as a result of the decomposition of N -acetyl-( S )-allyl-l-cysteine at the detector source, chromatographic separation was required to discriminate ( S )-allyl-l-cysteine and its metabolites on a reversed-phase C 18 analytical column with a gradient mobile phase consisting of 0.1% formic acid and acetonitrile. The calibration curves of ( S )-allyl-l-cysteine, ( S )-allyl-l-cysteine sulfoxide, N -acetyl-( S )-allyl-l-cysteine, and N -acetyl-( S )-allyl-l-cysteine sulfoxide were linear over each concentration range, and the lower limits of quantification were 0.1 µg/mL [( S )-allyl-l-cysteine and N -acetyl-( S )-allyl-l-cysteine] and 0.25 µg/mL [( S )-allyl-l-cysteine sulfoxide and N -acetyl-( S )-allyl-l-cysteine sulfoxide]. Acceptable intraday and inter-day precisions and accuracies were obtained at three concentration levels. The method satisfied the regulatory requirements for matrix effects, recovery, and stability. The validated LC-MS/MS method was successfully used to determine the concentration of ( S )-allyl-l-cysteine and its metabolites in rat plasma samples after the administration of ( S )-allyl-l-cysteine or aged garlic extract. Georg Thieme Verlag KG Stuttgart · New York.

  14. Distribution and Excretion of Arsenic Metabolites after Oral Administration of Seafood-Related Organoarsenicals in Rats

    Directory of Open Access Journals (Sweden)

    Yayoi Kobayashi

    2016-09-01

    Full Text Available Less information is available on the metabolism of organic arsenicals compared to inorganic arsenic in mammals. In the present study, we investigated tissue distribution, metabolism and excretion in rats of organoarsenicals, dimethylarsinic acid (DMAV, arsenobetaine (AB, arsenocholine (AC and trimethylarsine oxide (TMAOV. Among these animals, arsenic concentrations in red blood cells (RBCs and spleen increased remarkably only in the DMAV group. Hepatic arsenic concentration increased significantly only in the AC group. Approximately 17%, 72% and 60% of the dose was excreted in urine in two days in the DMAV, AB and AC groups, respectively; virtually the entire dose was excreted in urine in one day in the TMAOV group. On the other hand, approximately 18%, 0.2%, 0.5% and 0.1% of the dose was excreted in feces in two days in the DMAV, AB, AC and TMAOV groups, respectively. A large amount of arsenic was accumulated in RBCs in the form of protein-bound dimethylarsinous acid (DMAIII, and dimethylmonothioarsinic acid (DMMTAV, a reportedly toxic thio-arsenical, was found in urine and fecal extract in the DMAV group. These results suggest that intake of DMAV is a potential health hazard, given that the metabolites of DMAV, such as DMAIII and DMMTAV, are known to be highly toxic.

  15. Pharmacokinetics of anthraquinones in rat plasma after oral administration of a rhubarb extract.

    Science.gov (United States)

    Wu, Wenjin; Yan, Ru; Yao, Meicun; Zhan, Ying; Wang, Yitao

    2014-04-01

    A sensitive and specific LC-MS/MS method was developed for simultaneous determination of aloe-emodin, rhein, emodin, chrysophanol and physcion and their conjugates in rat plasma. The lower limit of quantitation of each anthraquinone was 0.020-0.040 µm. Intra-day and inter-day accuracies were 90.1-114.3% and the precisions were anthraquinone was detectable throughout the experimental period (36 h) and showed much higher plasma concentrations and AUC0-t . The free/total ratios of aloe-emodin, rhein and emodin were 6.5, 49.0 and 1.7% for Cmax and 3.7, 32.5 and 1.1% for AUC0-t , respectively. The dose-normalized AUC0-t and Cmax of the total of each anthraquinone were in the same descending order: rhein > emodin > chrysophanol > physcion > aloe-emodin. These findings reveal phase II conjugates as the dominant in vivo existing forms of rhubarb antharquinones and warrant a further study to evaluate their contribution to the herbal activity. Copyright © 2013 John Wiley & Sons, Ltd.

  16. Effect of flavonoid-containing extracts on the growth of transplanted sarcoma 45, peripheral blood and bone marrow condition after oral and intramuscular administration in rats

    Directory of Open Access Journals (Sweden)

    Nikita A. Navolokin

    2017-08-01

    Full Text Available Objective — Discovery of the apoptosis-inducing effects of flavonoid vagonin allowed to make an assumption of existence of similar effect in others flavonoids. This study of the effects of extracts from Gratīola officinālis, Helichrýsum arenárium and diploid forms of Zea mays on bone marrow and blood leucocytes at intramuscular and oral administration was carried out on rats bearing sarcoma 45. Earlier, the apoptosis-inducing effects were detected for these extracts but the toxic effects of extracts on blood and bone marrow have not been studied. Therefore, the aim of this study was to investigate the effects of these extracts on white blood cell count and bone marrow morphology. Material and Methods — The experiments were carried out on 48 male Wistar albino rats according to University's Animal Ethics Committee (Protocol № 13, 2011, Saratov, Russia and the relevant national agency regulating experiments on animals. We evaluated white blood cell count and bone marrow morphology in animals after oral and intramuscular administration of extracts. A growth rate of tumor was also ranked. Results — Oral and intramuscular administration of extracts from flavonoid-containing plants Zea mays and Gratīola officinālis causes normalization of myelocytic germ parameters in bone marrow of tumor-bearing rats and increase of lymphocyte percent in white blood cell count of blood and myelogram. Conclusion — Absence of toxic effects and normalization of myelocytic germ parameters in bone marrow of tumor-bearing rats after oral and intramuscular administration of extracts from flavonoid-containing plants Zea mays and Gratīola officinālis allows to recommend further study of the antitumor effect of these extracts.

  17. Appearance of circulating and tissue 14C-lipids after oral 14C-tripalmitate administration in the late pregnant rat

    International Nuclear Information System (INIS)

    Argiles, J.; Herrera, E.

    1989-01-01

    Studies were performed to determine whether and/or how dietary lipids participate in maternal hypertriglyceridemia during late gestation in the rat. After oral administration of glycerol-tri(1-14C)-palmitate, total radioactivity in plasma increased more rapidly in 20-day pregnant rats than in either 19-day pregnant rats or virgin controls. At the peak of plasma radioactivity, four hours after the tracer was administered, most of the plasma label corresponded to 14C-lipids in triglyceride-rich lipoproteins (d less than 1.006), and when expressed per micromol of triglyceride, values were higher in pregnant than in virgin rats. The difference was less after 24 hours, although at this time the level of 14C-lipids in d less than 1.006 lipoproteins was still higher in 20-day pregnant rats than in virgins. Tissue 14C-lipids, as expressed per gram of fresh weight, were similar in pregnant and virgin rats, but the values in mammary glands were much higher in the former group. Estimated recovery of administered radioactivity four hours after tracer in total white adipose tissue, mammary glands, and plasma lipids was higher in pregnant than in virgin rats. No difference was found between 20-day pregnant and virgin rats either in the label retained in the gastrointestinal tract or in that exhaled as 14C-CO2 during the first four hours following oral administration of 14C-tripalmitate. These findings plus the known maternal hyperphagia, indicate that in the rat at late pregnancy triglyceride intestinal absorption is unchanged or even enhanced and that dietary lipids actively contribute to both maternal hypertriglyceridemia and lipid uptake by the mammary gland

  18. Single, 14-Day, and 13-Week Repeated Dose Toxicity Studies of Daily Oral Gelidium elegans Extract Administration to Rats.

    Science.gov (United States)

    Choi, Jia; Ryu, Su-Jung; Kim, Kui-Jin; Kim, Hyung-Min; Chung, Hee-Chul; Lee, Boo-Yong

    2018-01-20

    Gelidium elegans extract (GEE) is derived from a red alga from the Asia-Pacific region, which has antioxidant, anti-adipogenic, and anti-hyperglycemic effects. However, detailed studies of the toxicology of GEE have not been performed. We evaluated the single oral dose toxicity of GEE in male and female Sprague-Dawley (CD) rats. GEE did not cause deaths or have toxic effects at dosages of 5000 mg/kg/day, although compound-colored stools and diarrhea were observed in both sexes, which lasted 5000 mg/kg. We next evaluated the repeated oral dose toxicity of GEE in CD rats over 14 days and 13 weeks. GEE did not induce any significant toxicological changes in either sex at 2000 mg/kg/day. Repeated oral dose toxicity studies showed no adverse effects, in terms of clinical signs, mortality, body mass, food consumption, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy, organ masses, or histopathology, at dosages of 500, 1000, or 2000 mg/kg/day. The no observed adverse effect level (NOAEL) for GEE is thus likely to be >2000 mg/kg/day, and no pathology was identified in potential target organs. Therefore, this study indicates that repeated oral dosing with GEE is safe in CD rats.

  19. Single, 14-Day, and 13-Week Repeated Dose Toxicity Studies of Daily Oral Gelidium elegans Extract Administration to Rats

    Directory of Open Access Journals (Sweden)

    Jia Choi

    2018-01-01

    Full Text Available Gelidium elegans extract (GEE is derived from a red alga from the Asia–Pacific region, which has antioxidant, anti-adipogenic, and anti-hyperglycemic effects. However, detailed studies of the toxicology of GEE have not been performed. We evaluated the single oral dose toxicity of GEE in male and female Sprague-Dawley (CD rats. GEE did not cause deaths or have toxic effects at dosages of 5000 mg/kg/day, although compound-colored stools and diarrhea were observed in both sexes, which lasted <2 days. Therefore, the LD50 of GEE is likely to be >5000 mg/kg. We next evaluated the repeated oral dose toxicity of GEE in CD rats over 14 days and 13 weeks. GEE did not induce any significant toxicological changes in either sex at 2000 mg/kg/day. Repeated oral dose toxicity studies showed no adverse effects, in terms of clinical signs, mortality, body mass, food consumption, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy, organ masses, or histopathology, at dosages of 500, 1000, or 2000 mg/kg/day. The no observed adverse effect level (NOAEL for GEE is thus likely to be >2000 mg/kg/day, and no pathology was identified in potential target organs. Therefore, this study indicates that repeated oral dosing with GEE is safe in CD rats.

  20. Oral administration of Saccharomyces boulardii ameliorates carbon tetrachloride-induced liver fibrosis in rats via reducing intestinal permeability and modulating gut microbial composition.

    Science.gov (United States)

    Li, Ming; Zhu, Lin; Xie, Ao; Yuan, Jieli

    2015-02-01

    To investigate the effects of orally administrated Saccharomyces boulardii (S. boulardii) on the progress of carbon tetrachloride (CCl4)-induced liver fibrosis, 34 male Wistar rats were randomly divided into four experimental groups including the control group (n = 8), the cirrhotic group (n = 10), the preventive group (n = 8), and the treatment group (n = 8). Results showed that the liver expression levels of collagen, type I, alpha 1 (Col1A1), alpha smooth muscle actin (αSMA), transforming growth factor beta (TGF-β) and the serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and malondialdehyde (MDA) increased significantly in cirrhotic rats compared with control and decreased by S. boulardii administration. Treatment of S. boulardii also attenuated the increased endotoxin levels and pro-inflammatory cytokines in CCl4-treated rats. And, these were associated with the changes of intestinal permeability and fecal microbial composition. Our study suggested that oral administration of S. boulardii can promote the liver function of CCl4-treated rats, and the preventive treatment of this probiotic yeast may decelerate the progress of liver fibrosis.

  1. Long-Term Effects of Chronic Oral Ritalin Administration on Cognitive and Neural Development in Adolescent Wistar Kyoto Rats

    Directory of Open Access Journals (Sweden)

    Jennifer L. Cornish

    2012-09-01

    Full Text Available The diagnosis of Attention Deficit Hyperactivity Disorder (ADHD often results in chronic treatment with psychostimulants such as methylphenidate (MPH, Ritalin®. With increases in misdiagnosis of ADHD, children may be inappropriately exposed to chronic psychostimulant treatment during development. The aim of this study was to assess the effect of chronic Ritalin treatment on cognitive and neural development in misdiagnosed “normal” (Wistar Kyoto, WKY rats and in Spontaneously Hypertensive Rats (SHR, a model of ADHD. Adolescent male animals were treated for four weeks with oral Ritalin® (2 × 2 mg/kg/day or distilled water (dH2O. The effect of chronic treatment on delayed reinforcement tasks (DRT and tyrosine hydroxylase immunoreactivity (TH-ir in the prefrontal cortex was assessed. Two weeks following chronic treatment, WKY rats previously exposed to MPH chose the delayed reinforcer significantly less than the dH2O treated controls in both the DRT and extinction task. MPH treatment did not significantly alter cognitive performance in the SHR. TH-ir in the infralimbic cortex was significantly altered by age and behavioural experience in WKY and SHR, however this effect was not evident in WKY rats treated with MPH. These results suggest that chronic treatment with MPH throughout adolescence in “normal” WKY rats increased impulsive choice and altered catecholamine development when compared to vehicle controls.

  2. Pharmacokinetics of opicapone, a third-generation COMT inhibitor, after single and multiple oral administration: A comparative study in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Gonçalves, Daniela [Laboratory of Pharmacology, Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra (Portugal); CNC – Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra (Portugal); Alves, Gilberto, E-mail: gilberto@fcsaude.ubi.pt [CNC – Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra (Portugal); CICS-UBI – Health Sciences Research Centre, University of Beira Interior, Av. Infante D. Henrique, 6200-506 Covilhã (Portugal); Fortuna, Ana [Laboratory of Pharmacology, Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra (Portugal); CNC – Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra (Portugal); Soares-da-Silva, Patrício [Department of Research and Development, BIAL – Portela & Ca S.A., Av. da Siderurgia Nacional, 4745-457 S. Mamede do Coronado (Portugal); MedInUP – Center for Drug Discovery and Innovative Medicines, University Porto, Porto (Portugal); Falcão, Amílcar [Laboratory of Pharmacology, Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra (Portugal); CNC – Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra (Portugal)

    2017-05-15

    Opicapone is a novel potent, reversible and purely peripheral catechol-O-methyltransferase inhibitor that has been developed to be used as an adjunct to levodopa/aromatic L-amino acid decarboxylase inhibitor therapy for Parkinson's disease. Thus, this study aimed to compare the plasma pharmacokinetics of opicapone and its active metabolite (BIA 9-1079) after the administration of single and multiple oral doses to rats. Wistar rats (n = 8 per group) were orally treated with single (30, 60 or 90 mg/kg) or multiple (30 mg/kg once-daily for seven consecutive days) oral doses of opicapone. Blood samples were collected up to 24 h post-dosing through a cannula introduced in the tail vein of rats. After quantifying opicapone and BIA 9-1079 in plasma, a non-compartmental pharmacokinetic analysis was performed. Opicapone was quickly absorbed (time to reach the maximum plasma concentration ≤ 2 h) in both dosage regimens and the extent of systemic exposure to opicapone increased approximately in a dose-proportional manner after single-dosing within the studied dose range (30–90 mg/kg). Opicapone and BIA 9-1079 showed a relatively short plasma elimination half-life (1.58–4.50 h) and a small systemic accumulation after multiple-dosing. Hence, no pharmacokinetic concerns are expected when opicapone is administered with a once-daily dosing regimen. - Highlights: • Opicapone is relatively rapid absorbed after oral administration to rats. • Systemic exposure to opicapone increases approximately in a dose-proportional manner. • Opicapone and BIA 9-1079 show a small systemic accumulation after multiple-dosing.

  3. Comparative pharmacokinetics and tissue distribution profiles of lignan components in normal and hepatic fibrosis rats after oral administration of Fuzheng Huayu recipe.

    Science.gov (United States)

    Yang, Tao; Liu, Shan; Zheng, Tian-Hui; Tao, Yan-Yan; Liu, Cheng-Hai

    2015-05-26

    Fuzheng Huayu recipe (FZHY) is formulated on the basis of Chinese medicine theory in treating liver fibrosis. To illuminate the influence of the pathological state of liver fibrosis on the pharmacokinetics and tissue distribution profiles of lignan components from FZHY. Male Wistar rats were randomly divided into normal group and Hepatic fibrosis group (induced by dimethylnitrosamine). Six lignan components were detected and quantified by ultrahigh performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS)in the plasma and tissue of normal and hepatic fibrosis rats. A rapid, sensitive and convenient UHPLC-MS/MS method has been developed for the simultaneous determination of six lignan components in different rat biological samples successfully. After oral administration of FZHY at a dose of 15g/kg, the pharmacokinetic behaviors of schizandrin A (SIA), schizandrin B (SIB), schizandrin C (SIC), schisandrol A (SOA), Schisandrol B (SOB) and schisantherin A (STA) have been significantly changed in hepatic fibrosis rats compared with the normal rats, and their AUC(0-t) values were increased by 235.09%, 388.44%, 223.30%, 669.30%, 295.08% and 267.63% orderly (Pdistribution results showed the amount of SIA, SIB, SOA and SOB were significant increased in heart, lung, spleen and kidney of hepatic fibrosis rats compared with normal rats at most of the time point (Pdistribution of lignan components in normal and hepatic fibrosis rats. The hepatic fibrosis could alter the pharmacokinetics and tissue distribution properties of lignan components in rats after administration of FZHY. The results might be helpful for guide the clinical application of this medicine. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  4. Pharmacokinetic study of harmane and its 10 metabolites in rat after intravenous and oral administration by UPLC-ESI-MS/MS.

    Science.gov (United States)

    Li, Shuping; Teng, Liang; Liu, Wei; Cheng, Xuemei; Jiang, Bo; Wang, Zhengtao; Wang, Chang-Hong

    2016-09-01

    Context The β-carboline alkaloid harmane is widely distributed in common foods, beverages and hallucinogenic plants. Harmane exerts potential in therapies for Alzheimer's and depression diseases. However, little information on its dynamic metabolic profiles and pharmacokinetics in vivo is currently available. Objective This study investigates the dynamic metabolic profiles and pharmacokinetic properties of harmane and its metabolites in rats in vivo. Materials and methods A highly selective, sensitive and rapid ultra-performance liquid chromatography combined with electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS) method was developed and well-validated for simultaneous quantitative determination of harmane and its uncertain endogenous metabolite harmine, as well as for semiquantitative determination of 10 harmane metabolites in rats after intravenous injection and oral administration of harmane at 1.0 and 30.0 mg/kg, respectively. Results The calibration curves of harmane and harmine showed excellent linearity within the concentration range of 1-2000 ng/mL with acceptable accuracy, precision, selectivity, recovery, matrix effect and stability. Ten metabolites, including harmane but not harmine, were detected and identified after intravenous and oral administration of harmane. The absolute bioavailability of harmane following an oral dose was 19.41 ± 3.97%. According to the AUC0-t values of all the metabolites, the metabolic levels of phase II metabolites were higher than those of phase I metabolites, and the sulphation pathways were the dominant metabolic routes for harmane in both routes of administration. Discussion and conclusion The pharmacokinetic properties of harmane and its 10 metabolites in rats were determined. Sulphate conjugation was the predominant metabolic process of harmane in rats.

  5. Absorption Kinetics of the Main Conjugated Linoleic Acid Isomers in Commercial-Rich Oil after Oral Administration in Rats.

    Science.gov (United States)

    Rodríguez-Alcalá, Luís M; Ares, Irma; Fontecha, Javier; Martínez-Larrañaga, María-Rosa; Anadón, Arturo; Martínez, María-Aránzazu

    2017-09-06

    This study aimed to assess the oral absorption and plasma kinetics of two main isomers contained in commercial conjugated linoleic acid (CLA)-rich oil (Tonalin TG-80), rumenic acid (RA), and C18:2 trans-10, cis-12. The isomer plasma disposition after the single oral dose of 3000 mg of Tonalin TG-80/kg, containing 1200 mg/kg of each isomer, was studied in rats. The isomer plasma concentrations were determined by gas chromatography with flame ionization detection. The plasma kinetics showed rapid oral absorption of RA and C18:2 trans-10, cis-12 (t 1/2a 0.34 ± 0.09 and 0.53 ± 0.01 h) and slow elimination (t 1/2β 25.68 ± 3.29 and 18.12 ± 1.71 h); the maximal isomer plasma concentrations (C max ) of 8.48 ± 0.98 and 7.67 ± 0.80 μg mL -1 , respectively, were estimated at 2.08 ± 0.14 and 2.26 ± 0.11 h. Our results from a preclinical kinetic study in rats help to design future studies in humans for evaluating the CLA isomer dose-response.

  6. A 5-month toxicity study of the ethanol extract of the leaves of Heliotropium indicum in Sprague Dawley rats after oral administration.

    Science.gov (United States)

    Owolabi, M A; Oribayo, O O; Ukpo, G E; Mbaka, G O; Akindehin, O E

    2015-01-01

    Heliotropium indicum Linn. (Boraginaceae) is used in Nigerian traditional medicine to treat tuberculosis with treatment lasting for 3 months; however, information on its toxicity is scarce. This study investigated the safety of the leaves of Heliotropium indicum after a 5 month oral administration. The leaves of H. indicum were dried; extracted in 70% ethanol and concentrated to dryness. Swiss mice were administered orally with single doses of the extract (0.5 to 12.0 g/kg b.wt /day); mortality was examined for up to 14 days. In another study, the plant material (0.5 to 2.0 g/kg b.wt /day) were administered daily by oral gavage to Sprague Dawley rats. Body weight was monitored weekly, hematological, biochemical and organ parameters were determined at the end of the 1st, 2nd and 5th months of extract administration. The oral administration of the ethanol extract of H. indicum caused dose-dependent mortality. The LD50 was 9.78 g/kg b.wt for the Swiss mice; no harmful effect was observed on the liver and kidney except the testes which exhibited considerable inflammatory changes at the highest dose of 2.0 g/kg b.wt./day after the 5th month treatment. No significant difference (P>0.05) was shown in the enzyme study, marginal increase occurred in some haematological parameters. The increase in body weight of the treated rats after its initial reduction was consistent and significantly different (P<0.05) from their initial body weight. Prolonged administration of the crude leaf extract of H. indicum is considered to be safe and nontoxic at the doses studied. However, there is a probability of a negative effect on the testes at a higher dose of the extract.

  7. Toxicity effect of sub-chronic oral administration of class bitters® - a polyherbal formula on serum electrolytes and hematological indices in male Wistar albino rats

    Directory of Open Access Journals (Sweden)

    Kingsley C. Patrick-Iwuanyanwu

    2015-11-01

    Full Text Available The indiscriminate administration of readyto- use herbal formulations has become a major concern due to their potential health risk. The study investigated the effect of class bitters® (CB - a polyherbal formula prepared with Mondia whitei, Khaya senegalensis, Capparis erythrocarpus, Thoningia sanguinea and Xylopia aethiopica on serum electrolytes and hematological parameters in male Wistar albino rats. Two doses (500 and 1000 mg kg–1 of the polyherbal drugs were administered orally to male Wistar albino rats for a period of 9 weeks. The results showed that administration of 500 and 1000 mg kg–1 body weight of CB recorded a marked increase in the levels of sodium and chlorum when compared with control. However, there was a marked reduction in the levels of potassium and hydrogen carbonate. The results of the study also showed a significant (P≤0.05 decrease in the level of hematological parameters such as hemoglobin (Hb, packed cell volume (PCV, red blood cells (RBCs and platelets levels in the male Wistar albino rats, when compared with control. The marked decrease in Hb, PCV, RBCs and platelets concentrations observed in experimental rats in this study suggest that CB may have an adverse effect on erythropoiesis. These observations therefore showed that long-term administration of CB might cause renal disease and anemia.

  8. Fourteen days oral administration of therapeutic dosage of some ...

    African Journals Online (AJOL)

    Fourteen days oral administration of therapeutic dosage of some antibiotics reduced serum testosterone in male rats. FO Awobajo, Y Raji, II Olatunji-Bello, FT Kunle-Alabi, AO Adesanya, TO Awobajo ...

  9. Effect of oral administration of Bacillus coagulans B37 and Bacillus pumilus B9 strains on fecal coliforms, Lactobacillus and Bacillus spp. in rat animal model.

    Science.gov (United States)

    Haldar, Lopamudra; Gandhi, D N

    2016-07-01

    To investigate the effect of oral administration of two Bacillus strains on fecal coliforms, Lactobacillus and Bacillus spp. in rat animal model. An in vivo experiment was conducted for 49-day period on 36 adult male albino Wister rats divided equally into to four groups. After 7-day adaptation period, one group (T1) was fed on sterile skim milk along with basal diet for the next 28 days. Second (T2) and (T3) groups received spore biomass of Bacillus coagulans B37 and Bacillus pumilus B9, respectively, suspended in sterilized skim milk at 8-9 log colony-forming units/ml plus basal diet for 28 days, while control group (T4) was supplied with clean water along with basal diet. There was a 14-day post-treatment period. A total of 288 fecal samples (8 fecal collections per rat) were collected at every 7-day interval starting from 0 to 49 days and subjected to the enumeration of the counts of coliforms and lactobacilli and Bacillus spores using respective agar media. In vitro acid and bile tolerance tests on both the strains were performed. The rats those (T2 and T3) received either B. coagulans B37 or B. pumilus B9 spore along with non-fermented skim milk showed decrease (pBacillus spore counts as compared to the control group (T4) and the group fed only skim milk (T1). In vitro study indicated that both the strains were found to survive at pH 2.0 and 3.0 even up to 3 h and tolerate bile up to 2.0% concentration even after 12 h of exposure. This study revealed that oral administration of either B. coagulans B37 or B. pumilus B9 strains might be useful in reducing coliform counts accompanied by concurrent increase in lactobacilli counts in the intestinal flora in rats.

  10. Metabolism and disposition of [14C]brivanib alaninate after oral administration to rats, monkeys, and humans.

    Science.gov (United States)

    Gong, Jiachang; Gan, Jinping; Caceres-Cortes, Janet; Christopher, Lisa J; Arora, Vinod; Masson, Eric; Williams, Daphne; Pursley, Janice; Allentoff, Alban; Lago, Michael; Tran, Scott B; Iyer, Ramaswamy A

    2011-05-01

    Brivanib [(R)-1-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[1,2,4]triazin-6-yloxy)propan-2-ol, BMS-540215] is a potent and selective dual inhibitor of vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) signaling pathways. Its alanine prodrug, brivanib alaninate [(1R,2S)-2-aminopropionic acid 2-[4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yloxy]-1-methylethyl ester, BMS-582664], is currently under development as an oral agent for the treatment of cancer. This study describes the in vivo biotransformation of brivanib after a single oral dose of [(14)C]brivanib alaninate to intact rats, bile duct-cannulated (BDC) rats, intact monkeys, BDC monkeys, and humans. Fecal excretion was the primary route of elimination of drug-derived radioactivity in animals and humans. In BDC rats and monkeys, the majority of radioactivity was excreted in bile. Brivanib alaninate was rapidly and completely converted via hydrolysis to brivanib in vivo. The area under the curve from zero to infinity of brivanib accounted for 14.2 to 54.3% of circulating radioactivity in plasma in animals and humans, suggesting that metabolites contributed significantly to the total drug-related radioactivity. In plasma from animals and humans, brivanib was a prominent circulating component. All the metabolites that humans were exposed to were also present in toxicological species. On the basis of metabolite exposure and activity against VEGF and FGF receptors of the prominent human circulating metabolites, only brivanib is expected to contribute to the pharmacological effects in humans. Unchanged brivanib was not detected in urine or bile samples, suggesting that metabolic clearance was the primary route of elimination. The primary metabolic pathways were oxidative and conjugative metabolism of brivanib.

  11. Oral administration of O-2 lean, an anti-obesity herbal composition increased 5-HT metabolism, decreased food intake and body weight in overweight rats

    International Nuclear Information System (INIS)

    Bano, F.; Akhtar, N.; Haleem, D.J.

    2012-01-01

    Feeding behavior is complex processes controlled by the neruroendocrine system.5-HT play an important role in regulation of energy balance by suppressing food intake. Depletion of brain serotonin increase feeding behavior and develop obesity. Many serotoninergic compounds are available in market for the management of body weight. 02-Lean is an anti-obesity herbal formulation prepared by combination of different herbs. Oral administration of aqueous suspension of 02-Lean caused a significant decrease in body weight, food intake, and increase in whole brain 5-HT 5HIAA, tryptophan and plasma tryptophan in over weight rats treated with 0.096g/2ml 02-Lean in comparison to control group. (author)

  12. Development of microparticles for oral administration of the non-conventional radical scavenger IAC and testing in an inflammatory rat model.

    Science.gov (United States)

    Passerini, Nadia; Albertini, Beatrice; Sabatino, Marcello Di; Corace, Giuseppe; Luppi, Barbara; Canistro, Donatella; Vivarelli, Fabio; Cirillo, Silvia; Soleti, Antonio; Merizzi, Giulia; Paolini, Moreno

    2016-10-15

    The bis (1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl)-decandioate (IAC), is an innovative non- radical scavenger used with success in numerous disease models such as inflammation, neurological disorders, hepatitis and diabetes. The pharmacological treatments have been performed by the intraperitoneal route of administration, representing to date, the main limit for the drug use. The aim of this study was to develop a delivery system that allows the oral administration of IAC while maintaining its therapeutic efficacy. Solid Lipid Microparticles (SLMs) containing a theoretical 18% (w/w) of IAC have been produced by the spray congealing technology; three formulations have been tested (A, B and C) using different low melting point carriers (stearic acid, Compritol(®) HD5ATO and carnauba wax) alone or in combination. All IAC loaded SLMs exhibited a spherical shape, encapsulation efficiency higher than 94% and particle size suitable for the oral route. Administered per os at different dosages in an inflammation rat model, all SLMs demonstrated their efficacy in reducing oedema and alleviating pain, compared to the gold standards Indomethacin and Paracetamol. These results suggested that the SLMs are an efficacious delivery system for the oral administration of IAC, potentially useful for the treatment of others diseases related to an over production of free radicals. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Oral administration of marine collagen peptides from Chum Salmon skin enhances cutaneous wound healing and angiogenesis in rats.

    Science.gov (United States)

    Zhang, Zhaofeng; Wang, Junbo; Ding, Ye; Dai, Xiaoqian; Li, Yong

    2011-09-01

    A wound is a clinical entity which often poses problems in clinical practice. The present study was aimed to investigate the wound healing potential of administering marine collagen peptides (MCP) from Chum Salmon skin by using two wound models (incision and excision) in rats. Ninety-six animals were equally divided into the two wound models and then within each model animals were randomly divided into two groups: vehicle-treated group and 2 g kg(-1) MCP-treated group. Wound closure and tensile strength were calculated. Collagen deposition was assessed by Masson staining and hydroxyproline measurement. Angiogenesis was assessed by immunohistological methods. MCP-treated rats showed faster wound closure and improved tissue regeneration at the wound site, which was supported by histopathological parameters pertaining to wound healing. MCP treatment improved angiogenesis and helped form thicker and better organised collagen fibre deposition compared to vehicle-treated group. The results show the efficacy of oral MCP treatment on wound healing in animals. Copyright © 2011 Society of Chemical Industry.

  14. Hydrolysis is the dominating in vivo metabolism pathway for arctigenin: identification of novel metabolites of arctigenin by LC/MS/MS after oral administration in rats.

    Science.gov (United States)

    Gao, Qiong; Zhang, Yufeng; Wo, Siukwan; Zuo, Zhong

    2013-04-01

    The phenylpropanoid dibenzylbutyrolactone lignan arctigenin, a key component found in Arctium lappa, or burdock, has been reported with a variety of therapeutic effects including anticancer, anti-inflammation, and antivirus effects. Using LC/MS/MS, three novel metabolites of arctigenin, namely, arctigenic acid, arctigenin-4-O'-glucuronide, and 4-O-demethylarctigenin were identified after oral administration of arctigenin in rats for the first time. Another potential metabolite of arctigenin, arctigenin-4'-O-sulfate, was identified in vitro but not in vivo. Structure of arctigenic acid, the major metabolite of arctigenin, was confirmed by 13C-NMR and 1H-NMR. Rapid hydrolysis in plasma was identified as the major metabolic pathway of arctigenin after its oral administration, with Vmax, Km, and Clint in rat plasma determined to be 2.21 ± 0.12 nmol/min/mg, 89.12 ± 9.44 µM, and 24.74 µL/min/mg, respectively. Paraoxonase 1 was further confirmed to be the enzyme responsible for arctigenin hydrolysis, with Vmax, Km, and Clint determined to be 55.39 ± 1.49 nmol/min/mg, 300.3 ± 10.86 µM, and 184.45 µL/min/mg, respectively. Georg Thieme Verlag KG Stuttgart · New York.

  15. Determination and Pharmacokinetic Study of Three Diterpenes in Rat Plasma by UHPLC-ESI-MS/MS after Oral Administration of Rosmarinus officinalis L. Extract

    Directory of Open Access Journals (Sweden)

    Liqian Wang

    2017-06-01

    Full Text Available Rosmarinus officinalis L. is commonly used as a spice and flavoring agent. Diterpenes are the main active compounds of R. officinalis. An Ultra High Performance Liquid Chromatography-Tandem Mass Spectrometry (UHPLC-ESI-MS/MS method was developed for the determination of carnosol, rosmanol, and carnosic acid isolated from R. officinalis in rat plasma, and applied to a pharmacokinetic study after oral administration of R. officinalis extract. Sample preparation involved a liquid-liquid extraction of the analytes with ethyl acetate. Butylparaben was employed as an internal standard (I.S.. Chromatographic separation was carried out on a C18 column (ACQUITY UPLC® HSS T3, 1.8 μm, 2.1 mm × 100 mm with a gradient system consisting of the mobile phase solution A (0.1% formic acid in water and solution B (acetonitrile at the flow rate of 0.3 mL/min. The quantification was obtained using multiple reaction monitoring (MRM mode with electrospray ionization (ESI. The UHPLC-MS/MS assay was validated for linearity, accuracy, precision, extraction recovery, matrix effect and stability. This study described a simple, sensitive and validated UHPLC-MS/MS method for the simultaneous determination of three diterpene compounds in rat plasma after oral administration of R. officinalis extract, and investigated on their pharmacokinetic studies as well.

  16. Simultaneous Determination of Seven Phenolic Acids in Rat Plasma Using UHPLC-ESI-MS/MS after Oral Administration of Echinacea purpurea Extract

    Directory of Open Access Journals (Sweden)

    Yan Du

    2017-09-01

    Full Text Available A rapid and sensitive Ultra High Performance Liquid Chromatography Electrospray Ionization Tandem Mass Spectrometry (UHPLC-ESI-MS/MS method was developed and validated to simultaneously determine the concentration of seven phenolic acids (syringic acid, ferulic acid, caffeic acid, vanillic acid, p-coumaric acid, 3,4-dihydroxybenzoic acid and 4-hydroxybenzoic acid in rat plasma after oral administration of Echinacea purpurea extract. After mixing with the internal standard (IS, butylparaben, plasma samples were prepared by liquid–liquid extraction with ethyl acetate. The separation was performed using the Agilent Eclipse Plus C18 column (1.8 μm, 2.1 mm × 50 mm with a gradient system consisting of solution A (0.1% acetic acid in water and solution B (methanol at a flow rate of 0.3 mL/min. The detection was accomplished by a multiple reaction monitoring (MRM mode with electrospray ionization (ESI. The method was validated in terms of linearity, precision, accuracy, extraction recovery, matrix effect and stability. This method was successfully applied to study the pharmacokinetic properties of the seven compounds after oral administration of Echinacea purpurea extract in rats.

  17. Accumulation of Arsenic Speciation and In Vivo Toxicity Following Oral Administration of a Chinese Patent Medicine Xiao-Er-Zhi-Bao-Wan in Rats

    Directory of Open Access Journals (Sweden)

    Jiaoyang Luo

    2017-07-01

    Full Text Available Realgar-containing traditional Chinese medicines such as Xiao-Er-Zhi-Bao-Wan (XEZBW, have been widely used for thousands of years. However, events associated with arsenic-induced ailments have increasingly become a public concern. To address the toxicity of XEZBW, we studied the histopathology and blood biochemistry of rats exposed to XEZBW using technology like high-performance liquid chromatography-inductively coupled mass spectrometry to determine arsenic speciation. Our results demonstrated that dimethylarsinic acid (DMA increased from 18.57 ± 7.45 to 22.74 ± 7.45 ng/g in rat kidney after oral administration for 7 and 14 days, which was 10-fold higher than the levels observed in controls. Trivalent arsenite As(III showed a large increase on day 7 (26.99 ± 1.98 ng/g, followed by a slight decrease on day 14 (13.67 ± 6.48 ng/g. Total arsenic levels on day 7 (185.52 ± 24.56 ng/g and day 14 (198.57 ± 26.26 ng/g were nearly twofold higher than that in the control group (92.77 ± 14.98 ng/g. Histopathological analysis showed mild injury in the liver and kidney of rats subjected to oral administration of realgar for 14 days. As in the XEZBW groups, a mild injury in these organs was observed after administration for 14 days. This study inferred that the toxicity of arsenic was concentration- and time-dependent. The accumulation of DMA, a byproduct of choline metabolism, was responsible for inducing higher toxicity. Therefore, we concluded that measuring the levels of DMA, instead of total arsenic, might be more suitable for evaluating the toxicity of realgar-containing traditional Chinese medicines.

  18. NMR-based metabonomic study of the sub-acute toxicity of titanium dioxide nanoparticles in rats after oral administration

    Science.gov (United States)

    Bu, Qian; Yan, Guangyan; Deng, Pengchi; Peng, Feng; Lin, Hongjun; Xu, Youzhi; Cao, Zhixing; Zhou, Tian; Xue, Aiqin; Wang, Yanli; Cen, Xiaobo; Zhao, Ying-Lan

    2010-03-01

    As titanium dioxide nanoparticles (TiO2 NPs) are widely used commercially, their potential toxicity on human health has attracted particular attention. In the present study, the oral toxicological effects of TiO2 NPs (dosed at 0.16, 0.4 and 1 g kg - 1, respectively) were investigated using conventional approaches and metabonomic analysis in Wistar rats. Serum chemistry, hematology and histopathology examinations were performed. The urine and serum were investigated by 1H nuclear magnetic resonance (NMR) using principal components and partial least squares discriminant analysis. The metabolic signature of urinalysis in TiO2 NP-treated rats showed increases in the levels of taurine, citrate, hippurate, histidine, trimethylamine-N-oxide (TMAO), citrulline, α-ketoglutarate, phenylacetylglycine (PAG) and acetate; moreover, decreases in the levels of lactate, betaine, methionine, threonine, pyruvate, 3-D-hydroxybutyrate (3-D-HB), choline and leucine were observed. The metabonomics analysis of serum showed increases in TMAO, choline, creatine, phosphocholine and 3-D-HB as well as decreases in glutamine, pyruvate, glutamate, acetoacetate, glutathione and methionine after TiO2 NP treatment. Aspartate aminotransferase (AST), creatine kinase (CK) and lactate dehydrogenase (LDH) were elevated and mitochondrial swelling in heart tissue was observed in TiO2 NP-treated rats. These findings indicate that disturbances in energy and amino acid metabolism and the gut microflora environment may be attributable to the slight injury to the liver and heart caused by TiO2 NPs. Moreover, the NMR-based metabolomic approach is a reliable and sensitive method to study the biochemical effects of nanomaterials.

  19. NMR-based metabonomic study of the sub-acute toxicity of titanium dioxide nanoparticles in rats after oral administration

    International Nuclear Information System (INIS)

    Bu Qian; Lin Hongjun; Xu Youzhi; Cao Zhixing; Zhou Tian; Zhao Yinglan; Yan Guangyan; Cen Xiaobo; Deng Pengchi; Peng Feng; Xue Aiqin; Wang Yanli

    2010-01-01

    As titanium dioxide nanoparticles (TiO 2 NPs) are widely used commercially, their potential toxicity on human health has attracted particular attention. In the present study, the oral toxicological effects of TiO 2 NPs (dosed at 0.16, 0.4 and 1 g kg -1 , respectively) were investigated using conventional approaches and metabonomic analysis in Wistar rats. Serum chemistry, hematology and histopathology examinations were performed. The urine and serum were investigated by 1 H nuclear magnetic resonance (NMR) using principal components and partial least squares discriminant analysis. The metabolic signature of urinalysis in TiO 2 NP-treated rats showed increases in the levels of taurine, citrate, hippurate, histidine, trimethylamine-N-oxide (TMAO), citrulline, α-ketoglutarate, phenylacetylglycine (PAG) and acetate; moreover, decreases in the levels of lactate, betaine, methionine, threonine, pyruvate, 3-D-hydroxybutyrate (3-D-HB), choline and leucine were observed. The metabonomics analysis of serum showed increases in TMAO, choline, creatine, phosphocholine and 3-D-HB as well as decreases in glutamine, pyruvate, glutamate, acetoacetate, glutathione and methionine after TiO 2 NP treatment. Aspartate aminotransferase (AST), creatine kinase (CK) and lactate dehydrogenase (LDH) were elevated and mitochondrial swelling in heart tissue was observed in TiO 2 NP-treated rats. These findings indicate that disturbances in energy and amino acid metabolism and the gut microflora environment may be attributable to the slight injury to the liver and heart caused by TiO 2 NPs. Moreover, the NMR-based metabolomic approach is a reliable and sensitive method to study the biochemical effects of nanomaterials.

  20. NMR-based metabonomic study of the sub-acute toxicity of titanium dioxide nanoparticles in rats after oral administration

    Energy Technology Data Exchange (ETDEWEB)

    Bu Qian; Lin Hongjun; Xu Youzhi; Cao Zhixing; Zhou Tian; Zhao Yinglan [State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China); Yan Guangyan; Cen Xiaobo [National Chengdu Center for Safety Evaluation of Drugs, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China); Deng Pengchi [Analytical and Testing Center, Sichuan University, Chengdu 610041 (China); Peng Feng [Department of Thoracic Oncology of Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China); Xue Aiqin [Institute of Bioengineering, Zhejiang Sci-Tech University Road 2, Xiasha, Hangzhou 310018 (China); Wang Yanli, E-mail: alancenxb@sina.com [Tianjin Children' s Hospital, Tianjin 300074 (China)

    2010-03-26

    As titanium dioxide nanoparticles (TiO{sub 2} NPs) are widely used commercially, their potential toxicity on human health has attracted particular attention. In the present study, the oral toxicological effects of TiO{sub 2} NPs (dosed at 0.16, 0.4 and 1 g kg{sup -1}, respectively) were investigated using conventional approaches and metabonomic analysis in Wistar rats. Serum chemistry, hematology and histopathology examinations were performed. The urine and serum were investigated by {sup 1}H nuclear magnetic resonance (NMR) using principal components and partial least squares discriminant analysis. The metabolic signature of urinalysis in TiO{sub 2} NP-treated rats showed increases in the levels of taurine, citrate, hippurate, histidine, trimethylamine-N-oxide (TMAO), citrulline, {alpha}-ketoglutarate, phenylacetylglycine (PAG) and acetate; moreover, decreases in the levels of lactate, betaine, methionine, threonine, pyruvate, 3-D-hydroxybutyrate (3-D-HB), choline and leucine were observed. The metabonomics analysis of serum showed increases in TMAO, choline, creatine, phosphocholine and 3-D-HB as well as decreases in glutamine, pyruvate, glutamate, acetoacetate, glutathione and methionine after TiO{sub 2} NP treatment. Aspartate aminotransferase (AST), creatine kinase (CK) and lactate dehydrogenase (LDH) were elevated and mitochondrial swelling in heart tissue was observed in TiO{sub 2} NP-treated rats. These findings indicate that disturbances in energy and amino acid metabolism and the gut microflora environment may be attributable to the slight injury to the liver and heart caused by TiO{sub 2} NPs. Moreover, the NMR-based metabolomic approach is a reliable and sensitive method to study the biochemical effects of nanomaterials.

  1. Oral administration of thymoquinone mitigates the effect of cisplatin on brush border membrane enzymes, energy metabolism and antioxidant system in rat intestine.

    Science.gov (United States)

    Shahid, Faaiza; Farooqui, Zeba; Abidi, Subuhi; Parwez, Iqbal; Khan, Farah

    2017-10-01

    Cisplatin (CP) is a widely used chemotherapeutic agent that elicits severe gastrointestinal toxicity. Nigella sativa, a member of family Ranunculaceae, is one of the most revered medicinal plant known for its numerous health benefits. Thymoquinone (TQ), a major bioactive component derived from the volatile oil of Nigella sativa seeds, has been shown to improve gastrointestinal functions in animal models of acute gastric/intestinal injury. In view of this, the aim of the present study was to investigate the protective effect of TQ on CP induced toxicity in rat intestine and to elucidate the mechanism underlying these effects. Rats were divided into four groups viz. control, CP, TQ and CP+TQ. Animals in CP+TQ and TQ groups were orally administered TQ (1.5mg/kg bwt) with and without a single intraperitoneal dose of CP (6mg/kg bwt) respectively. The effect of TQ was determined on CP induced alterations in the activities of brush border membrane (BBM), carbohydrate metabolism, and antioxidant defense enzymes in rat intestine. TQ administration significantly mitigated CP induced decline in the specific activities of BBM marker enzymes, both in the mucosal homogenates and in the BBM vesicles (BBMV) prepared from intestinal mucosa. Furthermore, TQ administration restored the redox and metabolic status of intestinal mucosal tissue in CP treated rats. The biochemical results were supported by histopathological findings that showed extensive damage to intestine in CP treated rats and markedly preserved intestinal histoarchitecture in CP and TQ co-treated group. The biochemical and histological data suggest a protective effect of TQ against CP-induced gastrointestinal damage. Thus, TQ may have a potential for clinical application to counteract the accompanying gastrointestinal toxicity in CP chemotherapy. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  2. Comparative pharmacokinetic profiles of tectorigenin in rat plasma by UPLC-MS/MS after oral administration of Iris tectorum Maxim extract and pure tectoridin.

    Science.gov (United States)

    Yang, Min; Yang, Xiaolin; An, Jinmeng; Xiao, Wei; Wang, Zhenzhong; Huang, Wenzhe; Yang, Zhonglin; Li, Fei

    2015-10-10

    Iris tectorum Maxim, a well-known herb medicine, is commonly used for treatment of inflammation, cough, and pharyngitis for a long time in China. Tectoridin, main active ingredient of Iris tectorum Maxim, is often used for its quality control. This study was aimed to analyze the pharmacokinetic profile of tectorigenin (the metabolite of tectoridin) after oral administration of I. tectorum Maxim extract, and to compare the pharmacokinetic characterization of tectorigenin after oral administration of I. tectorum Maxim extract (ITME) and pure tectoridin (PT) in rats. In addition, a simple, reliable and sensitive UPLC-MS/MS method was developed for determination of tectorigenin in rat plasma, using kaempferol as internal standard. The processed samples were separated on a Poroshell 120 SB-C₁₈ column and detected by positive electrospray ionization in multiple reaction monitoring (MRM) mode. The method validation results indicated that the established method was simple, specific and reliable. The pharmacokinetic results showed that the plasma concentration of tectorigenin in ITME group was much higher than that of the PT group (p<0.01). Moreover, compared to PT group, t₁/₂ value and AUC(0-∞) value were also notably increased in ITME group (p<0.01). In conclusion, potential interaction exists between those chemical components in ITME, and the co-existing components in ITME could notably promote the absorption of tectoridin in rats, however, the exact compound(s) which enhance the absorption of tectoridin should be investigated in future study. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Pharmacokinetics difference of multiple active constituents from decoction and maceration of Fuzi Xiexin Tang after oral administration in rat by UPLC-MS/MS.

    Science.gov (United States)

    Zhang, Qian; Ma, Yue-ming; Wang, Zheng-tao; Wang, Chang-hong

    2014-04-01

    Fuzi Xiexin Tang (FXT) is a classic traditional Chinese medicine formula which has been employed in clinical for more than 1800 years. The distinctive preparation method (maceration) recorded in ancient time is different from one in modern clinical practice (decoction). Aim of this study is to investigate the pharmacokinetic difference of alkaloids, flavones and anthraquinones in rats after oral administration of decoction of FXT (DFXT, 30gkg(-1)), maceration of FXT (MFXT, 30gkg(-1)) and decoction of Aconiti Lateralis Radix Preparata (DAR, 6gkg(-1)) by a validated UPLC-MS/MS method. Plasma concentrations and pharmacokinetic parameters of 16 active constituents (aconitine, hypaconitine, mesaconitine, benzoylaconine, benzoylhypaconine, benzoylmesaconine, berberine, palmatine, jatrorrhizine, coptisine, baicalin, wogonin, wogonoside, emodin, aloe-emodin, rhein) in rat were quantified and compared. Different preparative methods resulted in significant difference on exposure and pharmacokinetic characteristics of alkaloids, flavones and anthraquinones from FXT, especially protoberberine alkaloids. Concentrations of monoester-diterpenoid alkaloids were below the LOD in rat plasma after administration of DFXT and MFXT because of the existence of other three herbs from FXT. Maceration could decrease the absorption of flavones while increased the absorption of anthraquinones. Cmax of emodin and rhein were 3.1 and 10.3 times increased, while eliminations of these two constituents were 8.0 and 19.0 times slower after administration of MFXT. Bioavailability of both flavones and anthraquinones increased after administration of MFXT, especially emodin and rhein increasing as much as 13.5 and 20.7 times. Herb-herb interaction between DAR and other three herbs from FXT significantly influenced the exposure of aconitum alkaloids. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Effects of sub acute oral administration of aqueous extract of ...

    African Journals Online (AJOL)

    The study evaluates the effects of sub acute oral administration (28 days) of aqueous extract of Stereospermum kunthianum stem bark on the body weight and haematological indices of rats. Treatments were administered by oral gavage once daily for a total of 28 days. The first group (control) received distilled water (5 ...

  5. Repeated oral administration of capsaicin increases anxiety-like ...

    Indian Academy of Sciences (India)

    This study was conducted to examine the psycho-emotional effects of repeated oral exposure to capsaicin, the principal active component of chili peppers. Each rat received 1 mL of 0.02% capsaicin into its oral cavity daily, and was subjected to behavioural tests following 10 daily administrations of capsaicin. Stereotypy ...

  6. Effects of Oral Administration of Nicotine on Organ Weight, Serum ...

    African Journals Online (AJOL)

    This study investigated the effects of oral administration of nicotine on body and reproductive organ weight, serum testosterone level and testicular histology in adult male rats. Forty male rats divided into five groups and treated for a period of 30 days with 0.5mg/kg (low dose) and 1.0mg/kg (high dose) body weight of ...

  7. Oral administration of Rauwolfia vomitoria extract has no untoward ...

    African Journals Online (AJOL)

    The effect of ethanolic extract of leaf and root of Rauwolfia vomitoria on kidney and liver functions in rats was investigated. Rats were given daily oral administration of ethanolic extracts of either root or leaf of R. vomitoria at two different concentrations (1.0 and 2.0 g/kg body weight) for a period of 14 days. Some biochemical ...

  8. Effect of oral administration of Bacillus coagulans B37 and Bacillus pumilus B9 strains on fecal coliforms, Lactobacillus and Bacillus spp. in rat animal model

    Directory of Open Access Journals (Sweden)

    Lopamudra Haldar

    2016-07-01

    Full Text Available Aim: To investigate the effect of oral administration of two Bacillus strains on fecal coliforms, Lactobacillus and Bacillus spp. in rat animal model. Materials and Methods: An in vivo experiment was conducted for 49-day period on 36 adult male albino Wister rats divided equally into to four groups. After 7-day adaptation period, one group (T1 was fed on sterile skim milk along with basal diet for the next 28 days. Second (T2 and (T3 groups received spore biomass of Bacillus coagulans B37 and Bacillus pumilus B9, respectively, suspended in sterilized skim milk at 8-9 log colony-forming units/ml plus basal diet for 28 days, while control group (T4 was supplied with clean water along with basal diet. There was a 14-day post-treatment period. A total of 288 fecal samples (8 fecal collections per rat were collected at every 7-day interval starting from 0 to 49 days and subjected to the enumeration of the counts of coliforms and lactobacilli and Bacillus spores using respective agar media. In vitro acid and bile tolerance tests on both the strains were performed. Results: The rats those (T2 and T3 received either B. coagulans B37 or B. pumilus B9 spore along with non-fermented skim milk showed decrease (p<0.01 in fecal coliform counts and increase (p<0.05 in both fecal lactobacilli and Bacillus spore counts as compared to the control group (T4 and the group fed only skim milk (T1. In vitro study indicated that both the strains were found to survive at pH 2.0 and 3.0 even up to 3 h and tolerate bile up to 2.0% concentration even after 12 h of exposure. Conclusions: This study revealed that oral administration of either B. coagulans B37 or B. pumilus B9 strains might be useful in reducing coliform counts accompanied by concurrent increase in lactobacilli counts in the intestinal flora in rats.

  9. Identification of rotundic acid metabolites after oral administration to rats and comparison with the biotransformation by Syncephalastrum racemosum AS 3.264.

    Science.gov (United States)

    Li, Hui; Yang, Bao; Cao, Di; Zhou, Lian; Wang, Qing; Rong, Li; Zhou, Xinghong; Jin, Jing; Zhao, Zhongxiang

    2018-02-20

    The objective of this study was to identify the metabolites of rotundic acid after oral administration to rats and compare the similarities with its biotransformation by Syncephalastrum racemosum AS 3.264 using ultra-high performance liquid chromatography coupled with quadrupole time of flight mass spectrometry. A total of fourteen metabolites were determined based on the mass spectrometry and chromatographic behaviors, among which eleven (M1-M3, M7-M14) and six (M2, M4-M8) metabolites were identified in rats and S. racemosum, respectively. Three identical metabolites (M2, M7 and M8) were found in rats and S. racemosum, indicating that there were metabolic similarities. Moreover, to confirm the results of mass spectrometry, three (M2, M4 and M7) metabolites were obtained by the means of amplifying incubation and their structures were determined by various spectroscopic analyses, and M4 was proved to be a previously undescribed compound. This results showed that in vitro assisted preparation by microbial transformation is a feasible and effective method of obtaining metabolites which are in low amounts and difficult to be prepared in vivo. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Segmental-dependent membrane permeability along the intestine following oral drug administration: Evaluation of a triple single-pass intestinal perfusion (TSPIP) approach in the rat.

    Science.gov (United States)

    Dahan, Arik; West, Brady T; Amidon, Gordon L

    2009-02-15

    In this paper we evaluate a modified approach to the traditional single-pass intestinal perfusion (SPIP) rat model in investigating segmental-dependent permeability along the intestine following oral drug administration. Whereas in the traditional model one single segment of the intestine is perfused, we have simultaneously perfused three individual segments of each rat intestine: proximal jejunum, mid-small intestine and distal ileum, enabling to obtain tripled data from each rat compared to the traditional model. Three drugs, with different permeabilities, were utilized to evaluate the model: metoprolol, propranolol and cimetidine. Data was evaluated in comparison to the traditional method. Metoprolol and propranolol showed similar P(eff) values in the modified model in all segments. Segmental-dependent permeability was obtained for cimetidine, with lower P(eff) in the distal parts. Similar P(eff) values for all drugs were obtained in the traditional method, illustrating that the modified model is as accurate as the traditional, throughout a wide range of permeability characteristics, whether the permeability is constant or segment-dependent along the intestine. Three-fold higher statistical power to detect segmental-dependency was obtained in the modified approach, as each subject serves as his own control. In conclusion, the Triple SPIP model can reduce the number of animals utilized in segmental-dependent permeability research without compromising the quality of the data obtained.

  11. Pharmacokinetic and pharmacodynamic herb-drug interaction of Andrographis paniculata (Nees) extract and andrographolide with etoricoxib after oral administration in rats.

    Science.gov (United States)

    Balap, Aishwarya; Atre, Bhagyashri; Lohidasan, Sathiyanarayanan; Sinnathambi, Arulmozhi; Mahadik, Kakasaheb

    2016-05-13

    Andrographis paniculata Nees (Acanthacae) is commonly used medicinal plant in the traditional. Unani and Ayurvedic medicinal systems. It has broad range of pharmacological effects such as hepatoprotective, antioxidant, antivenom, antifertility, inhibition of replication of the HIV virus, antimalarial, antifungal, antibacterial, antidiabetic, suppression of various cancer cells and anti-inflammatory properties. Andrographolide (AN) is one of the active constituent of the A. paniculata Nees extract (APE). They have been found in many traditional herbal formulations in India and proven to be effective as anti-inflammatory drug To evaluate the pharmacokinetic and pharmacodynamic (anti-arthritic) herb-drug interactions of A. paniculata Nees extract (APE) and pure andrographolide (AN) with etoricoxib (ETO) after oral co-administration in wistar rats. After oral co-administration of APE (200mg/Kg) and AN (60mg/kg) with ETO (10mg/kg) in rats, drug concentrations in plasma were determined using HPLC method. The main pharmacokinetic parameters of Cmax, tmax, t1/2, MRT, Vd, CL, and AUC were calculated by non-compartment model. Change in paw volume, mechanical nociceptive threshold, mechanical hyperalgesia, histopathology and hematological parameters were evaluated to study antiarthritic activity. Co-administration of ETO with APE and pure AN decreased systemic exposure level of each compound in vivo. The Cmax, AUC, t1/2 of ETO was decreased whereas Vd and CL of ETO was increased significantly after co-administration of ETO with pure AN and APE. In pharmacodynamic study, ETO alone and ETO+APE (10+200mg/kg) groups exhibited significant synergistic anti-arthritic activity as compared to groups ETO+AN, APE and AN alone. The results obtained from this study suggested that ETO, APE and pure AN existed pharmacokinetic herb-drug interactions in rat which is correlated with anti-arthritic study. Physicians and patients using A. paniculata should have the knowledge about its possible

  12. Oral administration of royal jelly restores tear secretion capacity in rat blink-suppressed dry eye model by modulating lacrimal gland function.

    Directory of Open Access Journals (Sweden)

    Toshihiro Imada

    Full Text Available Tears are secreted from the lacrimal gland (LG, a dysfunction in which induces dry eye, resulting in ocular discomfort and visual impairment. Honey bee products are used as a nutritional source in daily life and medicine; however, little is known about their effects on dry eye. The aim of the present study was to investigate the effects of honey bee products on tear secretion capacity in dry eye. We selected raw honey, propolis, royal jelly (RJ, pollen, or larva from commercially available honey bee products. Tear secretion capacity was evaluated following the oral administration of each honey bee product in a rat blink-suppressed dry eye model. Changes in tear secretion, LG ATP content, and LG mitochondrial levels were measured. RJ restored the tear secretion capacity and decrease in LG ATP content and mitochondrial levels to the largest extent. Royal jelly can be used as a preventative intervention for dry eye by managing tear secretion capacity in the LG.

  13. Simultaneous quantification of flavonoids in blood plasma by a high-performance liquid chromatography method after oral administration of Blumea balsamifera leaf extracts in rats.

    Science.gov (United States)

    Nessa, Fazilatun; Ismail, Zhari; Mohamed, Nornisah; Karupiah, Sundram

    2013-03-01

    The leaves of Blumea balsamifera are used as a folk medicine in kidney stone diseases in South-East Asia. Phytochemical investigation revealed leaves contained a number of flavonoids. In view of these, the present work was aimed to quantify and preliminary pharmacokinetic investigation of five flavonoids viz. dihydroquercetin-7,4¢-dimethyl ether (I), dihydroquercetin-4¢-methyl ether (II), 5,7,3¢,5¢-tetrahydroxyflavanone (III), blumeatin (IV) and quercetin (V) in rat plasma following oral administration (0.5g/Kg) of B. balsamifera leaf extract in rats. Quantification was achieved by using a validated, reproducible high-performance liquid chromatographic method. The mean recoveries of I, II, III, IV and V were 90.6, 93.4, 93.5, 91.2 and 90.3% respectively. The limit of quantification was 25 ng/mL for I and IV, 10 ng/mL for II and III and 100 ng/mL for V respectively. The within day and day-to-day precision for all the compounds were HPLC method herein was applied for pharmacokinetic studies and the main pharmacokinetic parameters were: t1/2 (hr) 5.8, 4.3, 2.9, 5.7 and 7.3, Cmax (ng/mL) 594.9, 1542.9 1659.9, 208.9 and 3040.4; Tmax (hr) 4.7, 1.0, 1.0, 3.5 and 2.3; AUC0-oo (ng hr/mL) 5040, 5893, 9260, 1064 and 27233 for I, II, III, IV and V respectively. The developed method was suitable for pharmacokinetic studies and this preliminary study also revealed significant absorption after oral dosing in rats.

  14. Integrated pharmacokinetics of major bioactive components in MCAO rats after oral administration of Huang-Lian-Jie-Du-Tang.

    Science.gov (United States)

    Zhu, Huaxu; Qian, Zhilei; Li, Huan; Guo, Liwei; Pan, Linmei; Zhang, Qichun; Tang, Yuping

    2012-05-07

    Huang-Lian-Jie-Du-Tang (HLJDT, or Oren-gedoku-to in Japanese), an important multi-herb remedy in China and other Asia countries, has been used clinically to treat cerebral ischemia for decades. According to the previous studies we have reported, an HPLC method was developed and validated for determination of berberine, palmatine, baicalin, baicalein and geniposide simultaneously in MCAO rat plasma after administration of HLJDT aqueous extract. A classified integral pharmacokinetic method was put forward after having compared the integrated concentration-time profile with that of single component. An AUC based weighting approach was used for integrated principle. The results indicated the classified integral pharmacokinetic profile of index components from HLJDT could reveal the pharmacokinetic behavior of original components, and was corresponding to the holistic pharmacological effects of anti-ischemia with HLJDT. This study was aimed to explore an approach that could be applied to integrate the pharmacokinetic behavior of different components derived from HLJDT. The integrated pharmacokinetic results also provided more information for further understanding of the clinical cerebrovascular disease in use of HLJDT. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  15. Short and long term modulation of tissue minerals concentrations following oral administration of black cumin (Nigella sativa L.) seed oil to laboratory rats.

    Science.gov (United States)

    Basheer, Irum; Qureshi, Irfan Zia

    2018-01-15

    Nigella sativa, or commonly called black cumin is a small herb of family Ranunculaceae is a well-known medicinal plant but its effects on tissue mineral concentrations of animal bodies is unknown. To study the effect of oral administration of fixed oil of black cumin seeds on tissues mineral content using laboratory rats as experimental model. Experimental animals were exposed to two oral doses of seed oil (60 and 120 ml kg -1 body weight). Short- and long term experiments lasted 24 h and 60 days respectively, with three replicates each. Oil extracted from black cumin seeds was subjected to GC-MS to identify chemical components. Following the wet digestion in nitric acid, samples of whole blood and organs of rats were subjected to atomic absorption spectrophotometry for determination of elements concentrations. Data were compared statistically at p < .05. Compared to control, Cr, Mn, Ni, Cu, Zn showed decrease, whereas Co, Na, Mg and K demonstrated increase, but Ca showed both increase and decrease in most of the tissues upon short term exposure to low and high doses of black cumin oil. During long term exposure, Cr, Fe, Mn, Cu exhibited decrease; Co, Na, Mg and Ca concentrations demonstrated an upregulation, whereas Ni and Zn showed increase and decrease in most of the tissues. Comparison of short term with long term experiments at low dose revealed increases in Fe, Zn, Cu, Mg, K and Ca, a decrease in Cr, Mn, Ni and Cu in most tissues, but both increase and decrease in Na. At high dose, an increase occurred in Fe, Ni, Zn, K, Ca, Mg, a decrease in Cr, while both increase and decrease in Cu, Co and Na concentrations. Our study demonstrates that oral administration of black cumin seeds oil to laboratory rats significantly alters tissue trace elements and electrolytes concentrations. The study appears beneficial but indicates modulatory role of black cumin oil as regards mineral metabolism with far reaching implications in health and disease. Copyright © 2017

  16. Simultaneous Determination and Pharmacokinetic Study of Quercetin, Luteolin, and Apigenin in Rat Plasma after Oral Administration of Matricaria chamomilla L. Extract by HPLC-UV

    Directory of Open Access Journals (Sweden)

    Xiaoxv Dong

    2017-01-01

    Full Text Available A simple and sensitive HPLC-UV method has been developed for the simultaneous determination of quercetin, luteolin, and apigenin in rat plasma after oral administration of Matricaria chamomilla L. extract. The flow rate was set at 1.0 ml/min and the detection wavelength was kept at 350 nm. The calibration curves were linear in the range of 0.11–11.36 μg/ml for quercetin, 0.11–11.20 μg/ml for luteolin, and 0.11–10.60 μg/ml for apigenin, respectively. The intraday and interday precisions (RSD were less than 8.32 and 8.81%, respectively. The lower limits of quantification (LLOQ of the three compounds were 0.11 μg/ml. The mean recoveries for quercetin, luteolin, and apigenin were 99.11, 95.62, and 95.21%, respectively. Stability studies demonstrated that the three compounds were stable in the preparation and analytical process. The maximum plasma concentration (Cmax was 0.29 ± 0.06, 3.04 ± 0.60, and 0.42 ± 0.10 μg/ml, respectively. The time to reach the maximum plasma concentration (Tmax was 0.79 ± 0.25, 0.42 ± 0.09, and 0.51 ± 0.13 h, respectively. The validated method was successfully applied to investigate the pharmacokinetics study of quercetin, luteolin, and apigenin in rat plasma after oral administration of M. chamomilla extract.

  17. Pharmacokinetics study of ferulic acid in rats after oral administration of γ-oryzanol under combined use of Tween 80 by LC/MS/MS.

    Science.gov (United States)

    Pan, Y; Cai, L; He, S; Zhang, Z

    2014-01-01

    γ-oryzanol (OZ) is a rich source of commercially-important bioactive phytochemicals, most of them of interest in nutrition, pharmacy and cosmetics. However, the poor solubility of OZ limited the use. In the paper, ultraviolet-visible (UV-Vis) analysis was conducted to analysis the solubilization of OZ under combined use of Tween 80 in vitro. In addition, to further confirm the solubilizing effect of Tween 80, a pharmacokinetic study of ferulic acid (FA) in rats after oral administration of OZ 100 mg/kg under combined use of Tween 80 though LCMS/MS was carried out. Solubility enhancement as high as 100-fold is achieved using 1% Tween 80 in vitro. Following oral administration of OZ-Tween 80 100 mg/kg, the values of Tmax, Cmax, AUC0-∞, T1/2Ka and MRT0-∞ were 46.667 ± 39.328, 129.498 ± 27.025, 63738.28 ± 599, 14.274 ± 7.309 and 859.592 ± 108.780 respectively. The values of T1/2Ka, AUC0-∞, MRT0-t, and Tmax showed up to increase 16%, 58%, 44% and 47% while Cmax and CL/F decreased 22% and 12%, respectively. The decreased Cmax value indicated that Tween 80 can hardly enhance the absorption of FA in rats. However, T1/2Ka and Tmax values showed that the absorption of FA was extended, which resulted the increased values of AUC0-∞ and MRT0-∞. Our results reveal that Tween 80 improves solubility of OZ in vitro and could enhance the bioavailability of OZ by extending its absorption and elimination.

  18. Toxicity evaluation of methoxy poly(ethylene oxide)-block-poly(ε-caprolactone) polymeric micelles following multiple oral and intraperitoneal administration to rats.

    Science.gov (United States)

    Binkhathlan, Ziyad; Qamar, Wajhul; Ali, Raisuddin; Kfoury, Hala; Alghonaim, Mohammed

    2017-09-01

    Methoxy poly(ethylene oxide)- block -poly(ɛ-caprolactone) (PEO- b -PCL) copolymers are amphiphilic and biodegradable copolymers designed to deliver a variety of drugs and diagnostic agents. The aim of this study was to synthesize PEO- b -PCL block copolymers and assess the toxic effects of drug-free PEO- b -PCL micelles after multiple-dose administrations via oral or intraperitoneal (ip) administration in rats. Assembly of block copolymers was achieved by co-solvent evaporation method. To investigate the toxicity profile of PEO- b -PCL micelles, sixty animals were divided into two major groups: The first group received PEO- b -PCL micelles (100 mg/kg) by oral gavage daily for seven days, while the other group received the same dose of micelles by ip injections daily for seven days. Twenty-four hours following the last dose, half of the animals from each group were sacrificed and blood and organs (lung, liver, kidneys, heart and spleen) were collected. Remaining animals were observed for further 14 days and was sacrificed at the end of the third week, and blood and organs were collected. None of the polymeric micelles administered caused any significant effects on relative organ weight, animal body weight, leucocytes count, % lymphocytes, liver and kidney toxicity markers and organs histology. Although the dose of copolymers used in this study is much higher than those used for drug delivery, it did not cause any significant toxic effects in rats. Histological examination of all the organs confirmed the nontoxic nature of the micelles.

  19. Toxicity evaluation of methoxy poly(ethylene oxide-block-poly(ε-caprolactone polymeric micelles following multiple oral and intraperitoneal administration to rats

    Directory of Open Access Journals (Sweden)

    Ziyad Binkhathlan

    2017-09-01

    Full Text Available Methoxy poly(ethylene oxide-block-poly(ɛ-caprolactone (PEO-b-PCL copolymers are amphiphilic and biodegradable copolymers designed to deliver a variety of drugs and diagnostic agents. The aim of this study was to synthesize PEO-b-PCL block copolymers and assess the toxic effects of drug-free PEO-b-PCL micelles after multiple-dose administrations via oral or intraperitoneal (ip administration in rats. Assembly of block copolymers was achieved by co-solvent evaporation method. To investigate the toxicity profile of PEO-b-PCL micelles, sixty animals were divided into two major groups: The first group received PEO-b-PCL micelles (100 mg/kg by oral gavage daily for seven days, while the other group received the same dose of micelles by ip injections daily for seven days. Twenty-four hours following the last dose, half of the animals from each group were sacrificed and blood and organs (lung, liver, kidneys, heart and spleen were collected. Remaining animals were observed for further 14 days and was sacrificed at the end of the third week, and blood and organs were collected. None of the polymeric micelles administered caused any significant effects on relative organ weight, animal body weight, leucocytes count, % lymphocytes, liver and kidney toxicity markers and organs histology. Although the dose of copolymers used in this study is much higher than those used for drug delivery, it did not cause any significant toxic effects in rats. Histological examination of all the organs confirmed the nontoxic nature of the micelles.

  20. Oral Metformin-Ascorbic Acid Co-Administration Ameliorates Alcohol ...

    African Journals Online (AJOL)

    Oral Metformin-Ascorbic Acid Co-Administration Ameliorates Alcohol-Induced Hepatotoxicity In Rats. ... Nigerian Quarterly Journal of Hospital Medicine ... the present in vivo animal study was to determine whether metformin-ascorbic acid co-administration also prevents alcoholic hepatotoxicity in chronic alcohol exposure.

  1. Distribution of 14C after oral administration of [U-14C]labeled methyl linoleate hydroperoxides and their secondary oxidation products in rats

    International Nuclear Information System (INIS)

    Oarada, M.; Miyazawa, T.; Kaneda, T.

    1986-01-01

    To study the toxicity of low molecular weight (LMW) compounds formed during the autoxidation of oils, 14 C-labeled primary monomeric compounds (methyl linoleate hydroperoxides) and secondary oxidation products, i.e., polymer and LMW compounds prepared from autoxidized methyl [U- 14 C]linoleate hydroperoxides (MLHPO) were orally administered to rats, and their radioactive distributions in tissues and organs were compared. The polymeric fraction consisted mainly of dimers of MLHPO. For the LMW fraction, 4-hydroxy-2-nonenal, 8-hydroxy methyl octanoate and 10-formyl methyl-9-decenoate were identified as major constituents by gas chromatography-mass spectrometry (GC-MS) after chemical reduction and derivatization. When LMW compounds were administered to rats, 14 CO 2 expiration and the excreted radioactivity in urine in 12 hr were significantly higher than those from polymer or MLHPO administration. Maximum 14 CO 2 expiration appeared 2-4 hr after the dose of LMW compounds. Radioactivity of the upper part of small intestines six hr after the dose of LMW compounds was higher than the values from administered polymer or MLHPO. The remaining radioactivity in the digestive contents and feces 12 hr after administration of LMW compounds was much lower than the values observed from administered polymer or MLHPO. Among internal organs, the liver contained the highest concentration of radioactivities from polymer, MLHPO and LMW fractions, and an especially higher level of radioactivity was found in liver six hr after the administration of LMW compounds. Six hours after the dose of LMW compounds, a relatively higher level of radioactivity also was detected in kidney, brain, heart and lung

  2. Induction of intestinal metaplasia in the glandular stomach of rats by x-irradiation prior to oral administration of N-methyl-N'-nitro-N-nitrosoguanidine

    Energy Technology Data Exchange (ETDEWEB)

    Fujii, I; Watanabe, H; Terada, Y; Naito, Y; Naito, M [Hiroshima Univ. (Japan). Research Inst. for Nuclear Medicine and Biology

    1980-12-01

    CD/CRJ rats were subjected to localized X-irradiation of the stomach and given N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in the drinking water. Rats given MNNG alone and non-treated rats were used as controls. Upon sacrifice at 15 months after the initial MNNG administration, intestinal metaplasia was observed; the histology was of complete type and the incidence was 100% in rats treated with X-rays and MNNG, whereas in rats treated with MNNG alone the intestinal metaplasia was of incomplete type and its incidence was 80%. However, the incidence of gastric cancer in rats treated with MNNG alone was 25%.

  3. Identification of major xanthones and steroidal saponins in rat urine by liquid chromatography-atmospheric pressure chemical ionization mass spectrometry technology following oral administration of Rhizoma Anemarrhenae decoction.

    Science.gov (United States)

    Ma, Chunhui; Wang, Longxing; Tang, Yihong; Fan, Mingsong; Xiao, Hongbin; Huang, Chenggang

    2008-10-01

    Rhizoma Anemarrhenae (Zhimu in Chinese), the dried rhizome of Anemarrhena asphodeloides Bge. (Fam. Liliaceae), is a well-known traditional Chinese medicinal herb and has been used clinically in China for centuries to cure various diseases. However, like other traditional Chinese medicines, the effective constituents of this medicine, especially the assimilation and metabolites in vivo, which are very important to show their effects, have not been systematically studied. In this paper, solid-phase extraction and liquid chromatography-atmospheric pressure chemical ionization mass spectrometry technologies were used to study the constituents absorbed into rat urine and their metabolites after oral administration of Rhizoma Anemarrhenae decoction. A total of 11 compounds, including two xanthones, three of their metabolites and six steroidal saponins, were identified in rat urine sample. They were neomangiferin (1), glucuronide and monomethyl conjugate of mangiferin (2), mangiferin (3), monomethyl conjugate of mangiferin (4), dimethyl conjugate of mangiferin (5), timosaponin N or timosaponin E1 (6), timosaponin BII (7), timosaponin BIII (8), anemarrhenasaponin I or anemarrhenasaponin II (9), timosaponin AII (10) and timosaponin AIII (11). The results would efficaciously narrow the potentially active compounds range in Rhizoma Anemarrhenae decoction, and pave a helpful way for follow-up mechanism of action research.

  4. Oral administration of Nigella sativa oil ameliorates the effect of cisplatin on membrane enzymes, carbohydrate metabolism and oxidative damage in rat liver

    Directory of Open Access Journals (Sweden)

    Zeba Farooqui

    Full Text Available Cisplatin (CP is a potent anti-cancer drug widely used against solid tumors. However, it exhibits pronounced adverse effects including hepatotoxicity. Several strategies were attempted to prevent CP hepatotoxicity but were not found suitable for therapeutic application. Nigella sativa has been shown to prevent/reduce the progression of certain type of cardiovascular, kidney and liver diseases. Present study investigates whether N. sativa oil (NSO can prevent CP induced hepatotoxic effects. Rats were divided into four groups viz. control, CP, NSO and CPNSO. Animals in CPNSO and NSO group were administered NSO (2 ml/kg bwt, orally with or without single hepatotoxic dose of CP (6 mg/kg bwt, i.p. respectively. CP hepatotoxicity was recorded by increased serum ALT and AST activities. CP treatment caused oxidant/antioxidant imbalances as reflected by increased lipid peroxidation and decreased enzymatic and non-enzymatic antioxidants. Furthermore, the activities of various carbohydrate metabolism and membrane enzymes were altered by CP treatment. In contrast, NSO administration to CP treated rats, markedly ameliorated the CP elicited deleterious alterations in liver. Histopathological observations showed extensive liver damage in CP treated animals while greatly reduced tissue injury in CPNSO group. In conclusion, NSO appears to protect CP induced hepatotoxicity by improving energy metabolism and strengthening antioxidant defense mechanism. Keywords: Cisplatin, Nigella sativa oil, Carbohydrate metabolism, Antioxidant

  5. The Effect of Chronic Oral Administration of Withania Somnifera Root on Learning and Memory in Diabetic Rats Using Passive Avoidance Test

    Directory of Open Access Journals (Sweden)

    M. Roghani

    2006-07-01

    Full Text Available Introduction & Objective: Diabetes mellitus (especially type I is accompanied with disturbances in learning, memory, and cognitive skills in the human society and experimental animals. Considering the potential anti-diabetic effect of the medicinal plant Withania somnifera (ashwagandha and the augmenting effect of its consumption on the memory and mental health, this study was conducted to evaluate the effect of chronic oral administration of ashwagandha root on learning and memory in diabetic rats using passive avoidance test. Materials & Methods: For this purpose, male Wistar diabetic rats were randomly divided into control, ashwagandha-treated control, diabetic, and ashwagandha-treated diabetic groups. Ashwagandha treatment continued for 1 to 2 months. For induction of diabetes, streptozotocin was injected i.p. at a single dose of 60 mg/kg. Serum glucose level was determined before the study and at 4th and 8th weeks after the experiment. In addition, for evaluation of learning and memory, initial latency (IL and step-through latency (STL were determined after 1 and 2 months using passive avoidance test. Results: It was found that one- and two-month administration of ashwagandha root at a weight ratio of 1/15 has not any significant hypoglycemic effect in treated control and diabetic groups. Furthermore, there was a significant increase (p<0.05 in IL in diabetic and ashwagandha-treated diabetic groups after two months compared to control group. In this respect, there was no significant difference between diabetic and ashwagandha-treated diabetic groups. In addition, STL significantly increased in ashwagandha-treated control group after 1 (p<0.01 and 2 (p<0.05 month in comparison to control group. On the other hand, STL significantly decreased (p<0.05 in diabetic group and significantly increased (p<0.05 in ashwagandha-treated diabetic group as compared to control group after two months. Conclusion: In summary, chronic oral administration of

  6. Alteration in plasma corticosterone levels following long term oral administration of lead produces depression like symptoms in rats.

    Science.gov (United States)

    Haider, Saida; Saleem, Sadia; Tabassum, Saiqa; Khaliq, Saima; Shamim, Saima; Batool, Zehra; Parveen, Tahira; Inam, Qurat-ul-ain; Haleem, Darakhshan J

    2013-03-01

    Lead toxicity is known to induce a broad range of physiological, biochemical and behavioral dysfunctions that may result in adverse effects on several organs, including the central nervous system. Long-term exposure to low levels of lead (Pb(2+)) has been shown to produce behavioral deficits in rodents and humans by affecting hypothalamic-pituitary-adrenal (HPA) axis. These deficits are thought to be associated with altered brain monoamine neurotransmission and due to changes in glucocorticoids levels. This study was designed to investigate the effects of Pb(2+)exposure on growth rate, locomotor activity, anxiety, depression, plasma corticosterone and brain serotonin (5-HT) levels in rats. Rats were exposed to lead in drinking water (500 ppm; lead acetate) for 5 weeks. The assessment of depression was done using the forced swimming test (FST). Estimation of brain 5-HT was determined by high-performance liquid chromatography with electrochemical detection. Plasma corticosterone was determined by spectrofluorimetric method. The present study showed that long term exposure to Pb(2+) significantly decreased the food intake followed by the decrease in growth rate in Pb(2+)exposed rats as compared to control group. No significant changes in open field activity were observed following Pb(2+)exposure while significant increase in anxiogenic effect was observed. Increased plasma corticosterone and decreased 5-HT levels were exhibited by Pb(2+)exposed rats as compared to controls. A significant increase in depressive like symptoms was exhibited by Pb(2+)exposed rats as compared to control rats. The results are discussed in the context of Pb(2+) inducing a stress-like response in rats leading to changes in plasma corticosterone and brain 5-HT levels via altering tryptophan pyrrolase activity.

  7. Effect of repeated oral administration of bifenthrin on lipid peroxidation and anti-oxidant parameters in Wistar rats.

    Science.gov (United States)

    Dar, Muneer Ahmad; Khan, Adil Mehraj; Raina, Rajinder; Verma, Pawan Kumar; Sultana, Mudasir

    2013-07-01

    The oxidative stress-inducing potential of the pyrethroid insecticide, bifenthrin, was evaluated in rats at 5.8 mg/kg body weight once daily for 20 or 30 days. Bifenthrin treated animals showed significantly increased lipid peroxidation, evidenced by increased blood malondialdehyde levels. Blood glutathione levels and activities of catalase and glutathione peroxidase decreased significantly in the bifenthrin treated animals after both 20 and 30 days of treatment, whereas, the activities of superoxide dismutase and glutathione S-transferase decreased significantly only on the 30th day. In conclusion, bifenthrin has a potential to induce severe oxidative stress in rats exposed to sublethal concentrations.

  8. Antihypertensive Properties of a Pea Protein Hydrolysate during Short- and Long-Term Oral Administration to Spontaneously Hypertensive Rats.

    Science.gov (United States)

    Girgih, Abraham T; Nwachukwu, Ifeanyi D; Onuh, John O; Malomo, Sunday A; Aluko, Rotimi E

    2016-05-01

    This study investigated short-term (24 h) and long-term (5 wk) systolic blood pressure (SBP)-lowering effects in spontaneously hypertensive rats (SHR) of a 5 kDa membrane pea protein hydrolysate permeate (PPH-5) produced through thermoase hydrolysis of pea protein isolate (PPI). Amino acid analysis showed that the PPH-5 had lower contents of sulfur-containing amino acids than the PPI. Size-exclusion chromatography indicated mainly low molecular weight (pea products decreased in the 4th and 5th wk, though SBP values of the treated rats were still lower than the untreated control. We conclude that the antihypertensive potency of PPH-5 may have been due to the presence of easily absorbed hydrophilic peptides. © 2016 Institute of Food Technologists®

  9. Oral administration of soybean peptide Vglycin normalizes fasting glucose and restores impaired pancreatic function in Type 2 diabetic Wistar rats.

    Science.gov (United States)

    Jiang, Hua; Feng, Jueping; Du, Zhongxia; Zhen, Hui; Lin, Mei; Jia, Shaohui; Li, Tao; Huang, Xinyuan; Ostenson, Claes-Goran; Chen, Zhengwang

    2014-09-01

    Vglycin, a natural 37-residue polypeptide isolated from pea seeds in which six half-cysteine residues are embedded in three pairs of disulfide bonds, is resistant to digestive enzymes and has antidiabetic potential. To investigate the pharmacological activity of Vglycin in vivo and to examine the mechanisms involved, the therapeutic effect of Vglycin in diabetic rats was examined. Diabetes was induced in Wistar rats by high-fat diet and multiple streptozotocin intraperitoneal injections. Diabetic rats were treated daily with Vglycin for 4 weeks. Body weight, food intake, fasting plasma glucose and insulin levels were assayed weekly. Glucose and insulin tolerance tests were conducted on Day 29. Subsequently, levels of p-Akt in the liver and pancreas and cleaved PARP, Pdx-1 and insulin in the pancreas were detected by immunoblotting. The morphology of the pancreas and the insulin expression in the pancreas were analyzed by hematoxylin-eosin staining and immunohistochemistry, respectively. Furthermore, human liver-derived cell lines were used to explore the in vitro effects of Vglycin on insulin sensitivity and glucose uptake. Chronic treatment with Vglycin normalized fasting glucose levels in diabetic rats. The improvement in glucose homeostasis and the increased insulin sensitivity mediated by restored insulin signaling likely contributed to decreased food intake and reduced body weight. Vglycin protected pancreatic cells from damage by streptozotocin. Although insulin synthesis and secretion in impaired β-cell were not significantly elevated, islets morphology was improved in the Vglycin-treated groups. These results suggest that Vglycin could be useful in Type 2 diabetes for restoring impaired insulin signaling, glucose tolerance and pancreatic function. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. LC-MS/MS Determination and Pharmacokinetic Study of Pedunculoside in Rat Plasma after Oral Administration of Pedunculoside and Ilex rotunda Extract

    Directory of Open Access Journals (Sweden)

    Waiou Zhao

    2015-05-01

    Full Text Available Ilex rotunda is widely used to treat many disorders as a traditional Chinese medicine (TCM containing 4%–5% pedunculoside (PDC. A rapid, selective, and sensitive liquid chromatography-tandem mass spectrometry method (LC-MS/MS was developed and validated to determine PDC in rat plasma by using 3β,19α-dihydroxyurs-12-en-28-oic acid 28-β-D-glucopyranosyl ester (DEOG as an internal standard. The analytes were extracted by protein precipitation and eluted on a C18 chromatography column using a mobile phase of methanol–H2O (70:30, v/v delivered at a flow rate of 0.6 mL/min. Detection was performed using positive ion electrospray ionization in multiple reaction monitoring modes. The assay was linear over the concentration range of 0.60 ng/mL to 200 ng/mL, with a quantification limit of 0.60 ng/mL. Intra-day and inter-day precisions (%RSD ranged from 2.12 to 9.51 for PDC, whereas the accuracy was within −7.83%~9.40%. The validated method was successfully applied to the pharmacokinetic study of PDC in rat plasma after oral administration of pure PDC and Ilex rotunda extract (IRE. Pharmacokinetic parameters of PDC in IRE, such as Cmax, AUC0–t, AUC0–∞, t1/2z, and CLz/F, statistically differed from those of the pure monomer (p < 0.01. However, Tmax and MRT showed no significant differences between the two groups. Results suggested that other coexisting components in IRE may decrease the absorption of PDC. Compound-compound interactions between PDC and other herbal extract components can alter the pharmacokinetic behavior of PDC. The study will be helpful in providing references for understanding the action mechanism and clinical application of Ilex rotunda.

  11. Identification of the Chemical Constituents in Simiao Wan and Rat Plasma after Oral Administration by GC-MS and LC-MS

    Directory of Open Access Journals (Sweden)

    Yunshuang Fan

    2017-01-01

    Full Text Available Simiao Wan (SMW, an important multiherbal formula used in traditional Chinese medicine, is extensively used to treat rheumatoid arthritis. However, the knowledge of the bioactive components of SMW remains unclear. Thus, gas chromatography–mass spectrometry (GC-MS and liquid chromatography–mass spectrometry (LC-MS were used to analyze the chemical constituents of volatile and nonvolatile extracts of SMW, as well as its absorbed components in rat plasma after oral SMW administration. Identification of several compounds was enabled by comparison of retention times, MS spectra, and MS/MS spectral data with the standard substance and reference materials reported in the literature. In the volatile extracts, GC-MS identified 26 compounds in vitro, three of which observed in blood by GC-MS. In the nonvolatile extracts, LC-MS identified 49 compounds in SMW; 18 compounds containing 7 prototype compounds, 5 metabolites, and 6 unknown compounds were absorbed by blood. The proposed GC-MS and LC-MS method was appropriate not only for the rapid screening and identification of multiple components of an SMW extract but also for screening its bioactive constituents in vivo. The proposed method could be a promising tool for the quality control of other Chinese herbal medicines.

  12. Determination of Muscone in Rats Plasma following Oral Administration of Artificial Musk: Using of Combined Headspace Gas Chromatography-Mass Spectrometry

    Directory of Open Access Journals (Sweden)

    Qibiao Wu

    2014-01-01

    Full Text Available To develop an analytical method for determination of plasma concentrations of muscone in rats following oral administration of artificial musk, with the aim of investigating the pharmacokinetic profile of artificial musk. Plasma samples were pretreated with acetonitrile to precipitate proteins. Headspace injection coupled with gas chromatography-mass spectrometry was used for quantitative analysis of muscone concentrations. A strong linear relationship was obtained for plasma muscone concentrations ranging from 75.6 to 7560 ng·mL−1  R2=0.9998, with the minimum detectable concentration being 25 ng·mL−1. The within-day and interday precision for determination of three different concentrations of muscone were favorable (RSD < 25%. The average absolute recovery ranged from 83.7 to 88.6%, with an average relative recovery of 100.5 to 109.8%. The method described was characterized by stability and reliability, and in the present study showed significant specificity and high sensitivity. This method would be applicable to the analysis of plasma concentrations of muscone in preclinical contexts, where artificial musk is used.

  13. Treatment of chemotherapy-induced neutropenia in a rat model by using multiple daily doses of oral administration of G-CSF-containing nanoparticles.

    Science.gov (United States)

    Su, Fang-Yi; Chuang, Er-Yuan; Lin, Po-Yen; Chou, Yi-Chun; Chen, Chiung-Tong; Mi, Fwu-Long; Wey, Shiaw-Pyng; Yen, Tzu-Chen; Lin, Kun-Ju; Sung, Hsing-Wen

    2014-04-01

    Chemotherapy-induced neutropenia often increases the likelihood of life-threatening infections. In this study, a nanoparticle (NP) system composed of chitosan and poly(γ-glutamic acid) conjugated with diethylene triamine pentaacetic acid (γPGA-DTPA) was prepared for oral delivery of granulocyte colony-stimulating factor (G-CSF), a hematopoietic growth factor. The therapeutic potential of this NP system for daily administration of G-CSF to treat neutropenia associated with chemotherapy was evaluated in a rat model. In vitro results indicate that the procedures of NP loading and release preserved the structural integrity and bioactivity of the G-CSF molecules adequately. Those results further demonstrated the enzymatic inhibition activity of γPGA-DTPA towards G-CSF against intestinal proteases. Additionally, the in vivo biodistribution study clearly identified accumulations of G-CSF in the heart, liver, bone marrow, and urinary bladder, an indication of systemic absorption of G-CSF; its relative bioavailability was approximately 13.6%. Moreover, significant glucose uptake was observed in bone marrow during G-CSF treatment, suggesting increased bone marrow metabolism and neutrophil production. Consequently, neutrophil count in the blood increased in a sustained manner; this fact may help a patient's immune system recover from the side effects of chemotherapy. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Oral Administration of the Japanese Traditional Medicine Keishibukuryogan-ka-yokuinin Decreases Reactive Oxygen Metabolites in Rat Plasma: Identification of Chemical Constituents Contributing to Antioxidant Activity

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    Yosuke Matsubara

    2017-02-01

    Full Text Available Insufficient detoxification and/or overproduction of reactive oxygen species (ROS induce cellular and tissue damage, and generated reactive oxygen metabolites become exacerbating factors of dermatitis. Keishibukuryogan-ka-yokuinin (KBGY is a traditional Japanese medicine prescribed to treat dermatitis such as acne vulgaris. Our aim was to verify the antioxidant properties of KBGY, and identify its active constituents by blood pharmacokinetic techniques. Chemical constituents were quantified in extracts of KBGY, crude components, and the plasma of rats treated with a single oral administration of KBGY. Twenty-three KBGY compounds were detected in plasma, including gallic acid, prunasin, paeoniflorin, and azelaic acid, which have been reported to be effective for inflammation. KBGY decreased level of the diacron-reactive oxygen metabolites (d-ROMs in plasma. ROS-scavenging and lipid hydroperoxide (LPO generation assays revealed that gallic acid, 3-O-methylgallic acid, (+-catechin, and lariciresinol possess strong antioxidant activities. Gallic acid was active at a similar concentration to the maximum plasma concentration, therefore, our findings indicate that gallic acid is an important active constituent contributing to the antioxidant effects of KBGY. KBGY and its active constituents may improve redox imbalances induced by oxidative stress as an optional treatment for skin diseases.

  15. Comparative tissue distribution profiles of five major bio-active components in normal and blood deficiency rats after oral administration of Danggui Buxue Decoction by UPLC-TQ/MS.

    Science.gov (United States)

    Shi, Xuqin; Tang, Yuping; Zhu, Huaxu; Li, Weixia; Li, Zhenhao; Li, Wei; Duan, Jin-ao

    2014-01-01

    Astragali Radix (AR) and Angelicae Sinensis Radix (ASR) were frequently combined and used in China as herbal pair called as Danggui Buxue Decoction (DBD) for treatment of blood deficiency syndrome, such as women's ailments. This study is to investigate the tissue distribution profiles of five major bio-active constituents (ferulic acid, caffeic acid, calycosin-7-O-β-glucoside, ononin and astragaloside IV) in DBD after oral administration of DBD in blood deficiency rats, and to compare the difference between normal and blood deficiency rats. The blood deficiency rats were induced by bleeding from orbit at the dosages of 5.0mLkg(-1) every day, and the experimental period was 12 days. At the finally day of experimental period, both normal and blood deficiency rats were orally administrated with DBD, and then the tissues samples were collected at different time points. Ferulic acid, caffeic acid, calycosin-7-O-β-glucoside, ononin and astragaloside IV in different tissues were detected simultaneously by UPLC-TQ/MS, and the histograms were drawn. The results showed that the overall trend was CLiver>CKidney>CHeart>CSpleen>CLung, CC-30min>CM-30min>CM-60min>CC-5min>CM-5min>CC-60min>CM-240min>CC-240min. The contents of the detected compounds in liver were more than that in other tissues no matter in normal or blood deficiency rats. Compared to normal rats, partial contents of the compounds in blood deficiency rats' tissues at different time points had significant difference (Pdistribution investigation in blood deficiency animals which is conducted by bleeding. And the results demonstrated that the five DBD components in normal and blood deficiency rats had obvious differences in some organs and time points, suggesting that the blood flow and perfusion rate of the organ were altered in blood deficiency animals. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. Pharmacokinetic Comparison of Seven Major Bio-Active Components in Normal and Blood Stasis Rats after Oral Administration of Herb Pair Danggui-Honghua by UPLC-TQ/MS

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    Yi Jin

    2017-10-01

    Full Text Available The compatibility between Danggui (Angelicae Sinensis Radix and Honghua (Carthami Flos is a known herb pair, which could activate blood circulation and dissipate blood stasis effects. In this paper, we quantified seven main bio-active components (hydroxysafflor yellow A, caffeic acid, p-coumaric acid, kaempferol-3-O-rutinoside, ferulic acid, 3-n-butylphthalide, and ligustilide in plasma samples in vivo by UPLC-TQ/MS method and investigatedwhether the pharmacokinetic (PK behaviors of the seven components could be altered in blood stasis rats after oral administration of the Gui-Hong extracts. It was found that the Cmax and AUC0-t of these components in blood stasis rats had increasing tendency compared with normal rats. Most components in model and normal rats had significant difference in some pharmacokinetic parameters, which indicated that the metabolism enzymes and transporters involved in the metabolism and disposition of these bio-active componentsmay bealtered in blood stasis rats. This study was the first report about the pharmacokinetic investigation between normal and blood stasis rats after oral administrationof Gui-Hong extracts, and these results are important and valuable for better clinical applications of Gui-Hong herb pair and relatedTCM formulae.

  17. Comparisons of pharmacokinetic and tissue distribution profile of four major bioactive components after oral administration of Xiang-Fu-Si-Wu Decoction effective fraction in normal and dysmenorrheal symptom rats.

    Science.gov (United States)

    Liu, Pei; Li, Wei; Li, Zhen-hao; Qian, Da-wei; Guo, Jian-ming; Shang, Er-xin; Su, Shu-lan; Tang, Yu-ping; Duan, Jin-ao

    2014-07-03

    Xiang-Fu-Si-Wu Decoction (XFSWD) has been widely used to treat primary dysmenorrhea in clinical practice for hundreds of years and shown great efficacy. One fraction of XFSWD, which was an elution product by macroporous adsorption resin from aqueous extract solution with 60% ethanol (XFSWE), showed great analgesic effect. The present study was conducted to investigate the possible pharmacokinetic and tissue distribution profiles of four major bioactive constituents (berberine, protopine, tetrahydrocoptisine and tetrahydropalmatine) after oral administration of XFSWE in dysmenorrheal symptom rats, and to compare the difference between normal and dysmenorrheal symptom rats. Estradiol benzoate and oxytocin were used to produce dysmenorrheal symptom rat model. The experimental period was seven days. At the final day of experimental period, both normal and dysmenorrheal symptom rats were orally administrated with XFSWE, and then the blood and tissues samples were collected at different time points. Berberine, protopine, tetrahydrocoptisine and tetrahydropalmatine in blood and tissue samples were determined by LC-MS/MS. Pharmacokinetic parameters were calculated from the plasma concentration-time data using non-compartmental methods. The differences of pharmacokinetic parameters among groups were tested by one-way analysis of variance (ANOVA). There were statistically significant differences (Pnormal and dysmenorrheal symptom rats that orally administered with same dosage of XFSWE. In tissue distribution study, the results showed that the overall trend was C(Spleen)>C(Liver)>C(Kidney)>C(Uterus)>C(Heart)>C(Lung)>C(Ovary)>C(Brain)>C(Thymus), C(M-60 min)>C(M-120 min)>C(M-30 min)>C(C-60 min)>C(C-120 min)>C(C-30 min). The contents of protopine in liver, spleen and uterus were more than that in other tissues of dysmenorrheal symptom rats. Compared to normal rats, partial contents of the compounds in dysmenorrheal symptom rats׳ tissues at different time points had significant

  18. Oral administration of undenatured native chicken type II collagen (UC-II) diminished deterioration of articular cartilage in a rat model of osteoarthritis (OA).

    Science.gov (United States)

    Bagi, C M; Berryman, E R; Teo, S; Lane, N E

    2017-12-01

    The aim of this study was to determine the ability of undenatured native chicken type II collagen (UC-II) to prevent excessive articular cartilage deterioration in a rat model of osteoarthritis (OA). Twenty male rats were subjected to partial medial meniscectomy tear (PMMT) surgery to induce OA. Immediately after the surgery 10 rats received vehicle and another 10 rats oral daily dose of UC-II at 0.66 mg/kg for a period of 8 weeks. In addition 10 naïve rats were used as an intact control and another 10 rats received sham surgery. Study endpoints included a weight-bearing capacity of front and hind legs, serum biomarkers of bone and cartilage metabolism, analyses of subchondral and cancellous bone at the tibial epiphysis and metaphysis, and cartilage pathology at the medial tibial plateau using histological methods. PMMT surgery produced moderate OA at the medial tibial plateau. Specifically, the deterioration of articular cartilage negatively impacted the weight bearing capacity of the operated limb. Immediate treatment with the UC-II preserved the weight-bearing capacity of the injured leg, preserved integrity of the cancellous bone at tibial metaphysis and limited the excessive osteophyte formation and deterioration of articular cartilage. Study results demonstrate that a clinically relevant daily dose of UC-II when applied immediately after injury can improve the mechanical function of the injured knee and prevent excessive deterioration of articular cartilage. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  19. Nickel Excretion in Urine after Oral Administration

    DEFF Research Database (Denmark)

    Menne, T.; Mikkelsen, H. I.; Solgaard, Per Bent

    1978-01-01

    In recent years the importance of internal exposure to nickel in patients with recurrent hand eczema and nickel allergy has become evident. The present study was performed in order to investigate the value of urinary nickel determinations as an index of oral nickel intake. After oral administration...

  20. Unraveling the rat blood genome-wide transcriptome after oral administration of lavender oil by a two-color dye-swap DNA microarray approach

    Directory of Open Access Journals (Sweden)

    Motohide Hori

    2016-06-01

    Full Text Available Lavender oil (LO is a commonly used essential oil in aromatherapy as non-traditional medicine. With an aim to demonstrate LO effects on the body, we have recently established an animal model investigating the influence of orally administered LO in rat tissues, genome-wide. In this brief, we investigate the effect of LO ingestion in the blood of rat. Rats were administered LO at usual therapeutic dose (5 mg/kg in humans, and following collection of the venous blood from the heart and extraction of total RNA, the differentially expressed genes were screened using a 4 × 44-K whole-genome rat chip (Agilent microarray platform; Agilent Technologies, Palo Alto, CA, USA in conjunction with a two-color dye-swap approach. A total of 834 differentially expressed genes in the blood were identified: 362 up-regulated and 472 down-regulated. These genes were functionally categorized using bioinformatics tools. The gene expression inventory of rat blood transcriptome under LO, a first report, has been deposited into the Gene Expression Omnibus (GEO: GSE67499. The data will be a valuable resource in examining the effects of natural products, and which could also serve as a human model for further functional analysis and investigation.

  1. Pharmacokinetics and brain distribution of tetrahydropalmatine and tetrahydroberberine after oral administration of DA-9701, a new botanical gastroprokinetic agent, in rats.

    Science.gov (United States)

    Jung, Ji Won; Kwon, Yong Sam; Jeong, Jin Seok; Son, Miwon; Kang, Hee Eun

    2015-01-01

    DA-9701, a new botanical gastroprokinetic agent, has potential for the management of delayed gastric emptying in Parkinson's disease if it has no central anti-dopaminergic activity. Therefore, we examined the pharmacokinetics of DA-9701 components having dopamine D2 receptor antagonizing activity, tetrahydropalmatine (THP) and tetrahydroberberine (THB), following various oral doses (80-328 mg/kg) of DA-9701. The distribution of THP and THB to the brain and/or other tissues was also evaluated after single or multiple oral administrations of DA-9701. Oral administration of DA-9701 yielded dose-proportional area under the plasma concentration-time curve (AUC0-8 h) and maximum plasma concentration (Cmax) values for THP and THB, indicating linear pharmacokinetics (except for THB at the lowest dose). THP and THB's large tissue-to-plasma concentration ratios indicated considerable tissue distribution. High concentrations of THP and THB in the stomach and small intestine suggest an explanation for DA-9701's potent gastroprokinetic activity. The maximum concentrations of THP and THB in brain following multiple oral DA-9701 for 7 d (150 mg/kg/d) was observed at 30 min after the last oral DA-9701 treatment: 131±67.7 ng/g for THP and 6.97±4.03 ng/g for THB. Although both THP and THB pass through the blood-brain barrier, as indicated by brain-to-plasma concentration ratios greater than unity (approximately 2-4), oral administration of DA-9701 at the effective dose in humans is not expected to lead to sufficient brain concentrations to exert central dopamine D2 receptor antagonism.

  2. Intravenous voriconazole after toxic oral administration

    NARCIS (Netherlands)

    Alffenaar, J.W.C.; Van Assen, S.; De Monchy, J.G.R.; Uges, D.R.A.; Kosterink, J.G.W.; Van Der Werf, T.S.

    In a male patient with rhinocerebral invasive aspergillosis, prolonged high-dosage oral administration of voriconazole led to hepatotoxicity combined with a severe cutaneous reaction while intravenous administration in the same patient did not. High concentrations in the portal blood precipitate

  3. Elucidation of Arctigenin Pharmacokinetics and Tissue Distribution after Intravenous, Oral, Hypodermic and Sublingual Administration in Rats and Beagle Dogs: Integration of In Vitro and In Vivo Findings.

    Science.gov (United States)

    Li, Jie; Li, Xin; Ren, Yu-Shan; Lv, Yuan-Yuan; Zhang, Jun-Sheng; Xu, Xiao-Li; Wang, Xian-Zhen; Yao, Jing-Chun; Zhang, Gui-Min; Liu, Zhong

    2017-01-01

    Although arctigenin ( AG ) has diverse bioactivities, such as anti-oxidant, anti-inflammatory, anti-cancer, immunoregulatory and neuroprotective activities, its pharmacokinetics have not been systematically evaluated. The purpose of this work was to identify the pharmacokinetic properties of AG via various experiments in vivo and in vitro . In this research, rats and beagle dogs were used to investigate the PK (pharmacokinetics, PK) profiles of AG with different drug-delivery manners, including intravenous (i.v), hypodermic injection (i.h), and sublingual (s.l) administration. The data shows that AG exhibited a strong absorption capacity in both rats and beagle dogs (absorption rate 100%), and a strong elimination ability ( t 1/2 beagle dog (25.9 ± 3.24%) > rat (15.7 ± 9%) > monkey (3.69 ± 0.12%). This systematic investigation of pharmacokinetic profiles of arctigenin (AG) in vivo and in vitro is worthy of further exploration.

  4. Detection and Specific Enumeration of Multi-Strain Probiotics in the Lumen Contents and Mucus Layers of the Rat Intestine After Oral Administration.

    Science.gov (United States)

    Lee, Hee Ji; Orlovich, David A; Tagg, John R; Fawcett, J Paul

    2009-12-01

    Although the detection of viable probiotic bacteria following their ingestion and passage through the gastrointestinal tract (GIT) has been well documented, their mucosal attachment in vivo is more difficult to assess. In this study, we investigated the survival and mucosal attachment of multi-strain probiotics transiting the rat GIT. Rats were administered a commercial mixture of the intestinal probiotics Lactobacillus acidophilus LA742, Lactobacillus rhamnosus L2H and Bifidobacterium lactis HN019 and the oral probiotic Streptococcus salivarius K12 every 12 h for 3 days. Intestinal contents, mucus and faeces were tested 6 h, 3 days and 7 days after the last dose by strain-specific enumeration on selective media and by denaturing gradient gel electrophoresis. At 6 h, viable cells and DNA corresponding to all four probiotics were detected in the faeces and in both the lumen contents and mucus layers of the ileum and colon. Viable probiotic cells of B. lactis and L. rhamnosus were detected for 7 days and L. acidophilus for 3 days after the last dose. B. lactis and L. rhamnosus persisted in the ileal mucus and colon contents, whereas the retention of L. acidophilus appeared to be relatively higher in colonic mucus. No viable cells of S. salivarius K12 were detected in any of the samples at either day 3 or 7. The study demonstrates that probiotic strains of intestinal origin but not of oral origin exhibit temporary colonisation of the rat GIT and that these strains may have differing relative affinities for colonic and ileal mucosa.

  5. Simultaneous Determination and Pharmacokinetic Study of Six Components in Rat Plasma by HPLC-MS/MS after Oral Administration of Acanthopanax sessiliflorus Fruit Extract

    Directory of Open Access Journals (Sweden)

    Peng Du

    2016-12-01

    Full Text Available A specific and reliable HPLC-MS/MS method was developed and validated for the simultaneous determination of protocatechuic acid (PCA, scopolin, (−-pinoresinol-4,4′-di-O-β-d-glucopyranoside (PDG, acanthoside D, acanthoside B and hyperin in rat plasma for the first time. The analytes were separated on a C18 column (50 × 2.1 mm, 1.8 µm and a triple-quadrupole mass spectrometer equipped with an electrospray ionization (ESI source was used for detection. The rat plasma sample was prepared using the protein precipitation procedure. The calibration curves were linear over a concentration range of 1.2–1200.0 ng/mL for PCA, 0.96–960.0 ng/mL for scopolin, 1.12–1120.0 ng/mL for PDG, 1.32–1320.0 ng/mL for acanthoside D, 0.99–990.0 ng/mL for acanthoside B and 1.01–1010.0 ng/mL for hyperin. The intra-day and inter-day precision was less than 11.4% and the relative error (RE was all within ±15%. The validated method was successfully applied to assess the pharmacokinetics characteristics after the extracts of Acanthopanax sessiliflorus fruits were orally administered to the Sprague-Dawley rat.

  6. Prevention of pathogenic Escherichia coli infection in mice and stimulation of macrophage activation in rats by an oral administration of probiotic Lactobacillus casei I-5.

    Science.gov (United States)

    Ishida-Fujii, Keiko; Sato, Rieko; Goto, Shingo; Yang, Xiao-Ping; Kuboki, Hiroshi; Hirano, Shin-Ichi; Sato, Michikatsu

    2007-04-01

    Lactobacillus casei I-5 isolated from an alcohol fermentation broth enhanced immunity and prevented pathogenic infection as a probiotic. Mice fed with I-5 cells for 11 days prior to an intraperitoneal challenge with pathogenic Escherichia coli Juhl exhibited a high survival rate compared with the control group. Rats fed with I-5 cells for 10 days significantly increased the phagocytosis of peritoneal macrophages. In a cell culture system employing peritoneal macrophages from rats, the I-5 administration activated NF-kappaB stimulated by LPS. It also enhanced LPS-stimulated IL-12 and TNF-alpha production, but not IL-6 production. These results show that L. casei I-5 effectively prevented infection by pathogenic E. coli possibly through the activation of peritoneal macrophages. The strain would be useful to prevent pathogenic microbial infections in humans and farm animals.

  7. Elucidation of Arctigenin Pharmacokinetics and Tissue Distribution after Intravenous, Oral, Hypodermic and Sublingual Administration in Rats and Beagle Dogs: Integration of In Vitro and In Vivo Findings

    Directory of Open Access Journals (Sweden)

    Jie Li

    2017-06-01

    Full Text Available Although arctigenin (AG has diverse bioactivities, such as anti-oxidant, anti-inflammatory, anti-cancer, immunoregulatory and neuroprotective activities, its pharmacokinetics have not been systematically evaluated. The purpose of this work was to identify the pharmacokinetic properties of AG via various experiments in vivo and in vitro. In this research, rats and beagle dogs were used to investigate the PK (pharmacokinetics, PK profiles of AG with different drug-delivery manners, including intravenous (i.v, hypodermic injection (i.h, and sublingual (s.l administration. The data shows that AG exhibited a strong absorption capacity in both rats and beagle dogs (absorption rate < 1 h, a high absorption degree (absolute bioavailability > 100%, and a strong elimination ability (t1/2 < 2 h. The tissue distributions of AG at different time points after i.h showed that the distribution of AG in rat tissues is rapid (2.5 h to reach the peak and wide (detectable in almost all tissues and organs. The AG concentration in the intestine was the highest, followed by that in the heart, liver, pancreas, and kidney. In vitro, AG were incubated with human, monkey, beagle dog and rat liver microsomes. The concentrations of AG were detected by UPLC-MS/MS at different time points (from 0 min to 90 min. The percentages of AG remaining in four species’ liver microsomes were human (62 ± 6.36% > beagle dog (25.9 ± 3.24% > rat (15.7 ± 9% > monkey (3.69 ± 0.12%. This systematic investigation of pharmacokinetic profiles of arctigenin (AG in vivo and in vitro is worthy of further exploration.

  8. Determination of isoorientin levels in rat plasma after oral administration of Vaccinum bracteatum Thunb. methanol extract by high-performance liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Kim, Min-Ji; Kwon, Seung-Hwan; Jang, Choon-Gon; Maeng, Han-Joo

    2018-01-15

    A simple, sensitive and rapid liquid chromatography tandem mass spectrometry method (LC-MS/MS) was developed and validated for the determination of plasma isoorientin levels in rats. After simple protein precipitation using methanol, chromatographic analysis was performed using a Synergi 4μ polar-RP 80A column (150 × 2.0 mm, 4μm) under isocratic conditions and a mobile phase consisting of 0.1% formic acid in water and methanol (80:20, v/v) at a flow rate of 0.2 mL/min. In positive electrospray ionization mode, the protonated precursor and product ion transitions of isoorientin (m/z 449.0 → 299.1) and of puerarin (the internal standard; m/z 417.1 → 297.1) were acquired by multiple reaction monitoring. Calibration curves obtained for plasma showed good linearity over the concentration range 1-1000 ng/mL. The lower limit of quantification was 1 ng/mL. Intra- and inter-day precisions were within 8.8% relative standard deviation. Accuracies ranged from 92.1 and 109.7%. The isoorientin stability in rat plasma under typical handling/storage conditions also found to be acceptable. The developed method was applied successfully to a pharmacokinetic study of isoorientin orally administered as the methanol extract of Vaccinium bracteatum Thunb. or administered as pure isoorientin. Copyright © 2018 John Wiley & Sons, Ltd.

  9. Comparison of pharmacokinetic behavior of two iridoid glycosides in rat plasma after oral administration of crude Cornus officinals and its jiuzhipin by high performance liquid chromatography triple quadrupole mass spectrometry combined with multiple reactions monitoring mode

    Science.gov (United States)

    Chen, Xiaocheng; Cao, Gang; Jiang, Jianping

    2014-01-01

    Objective: The present study examined the pharmacokinetic profiles of two iridoid glycosides named morroniside and loganin in rat plasma after oral administration of crude and processed Cornus officinals. Materials and Methods: A rapid, selective and specific high-performance liquid chromatography/electrospray ionization tandem mass spectrometry with multiple reactions monitoring mode was developed to simultaneously investigate the pharmacokinetic profiles of morroniside and loganin in rat plasma after oral administration of crude C. officinals and its jiuzhipin. Results: The morroniside and loganin in crude and processed C. officinals could be simultaneously determined within 7.4 min. Linear calibration curves were obtained over the concentration ranges of 45.45-4800 ng/mL for all the analytes. The intra-and inter-day precisions relative standard deviation was lesser than 2.84% and 4.12%, respectively. Conclusion: The pharmacokinetic parameters of two iridoid glucosides were also compared systematically between crude and processed C. officinals. This paper provides the theoretical proofs for further explaining the processing mechanism of Traditional Chinese Medicines. PMID:24914290

  10. Enhanced Absorption Study of Ginsenoside Compound K (20-O-β-(D-Glucopyranosyl-20(S-protopanaxadiol after Oral Administration of Fermented Red Ginseng Extract (HYFRG™ in Healthy Korean Volunteers and Rats

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    Il-Dong Choi

    2016-01-01

    Full Text Available To evaluate the pharmacokinetics of compound K after oral administration of HYFRG and RG in humans, an open-label, randomized, single-dose, fasting, and one-period pharmacokinetic study was conducted. After oral administration of a single 3 g dose of HYFRG and RG to 24 healthy Korean males, the mean (±SD of AUC0–t and Cmax of compound K from HYFRG were 1466.83 ± 295.89 ng·h/mL and 254.45 ± 51.20 ng/mL, being 115.2- and 80-fold higher than those for RG (12.73 ± 7.83 ng·h/mL and 3.18 ± 1.70 ng/mL, respectively; in case of Sprague Dawley rats the mean (±SD of AUC0–t and Cmax of compound K from HYFRG was 58.03 ± 32.53 ng·h/mL and 15.19 ± 10.69 ng/mL, being 6.3- and 6.0-fold higher than those from RG (9.21 ± 7.52 ng·h/mL and 2.55 ± 0.99 ng/mL, respectively. Tmax of compound K in humans and rats was 2.54 ± 0.92 and 3.33 ± 0.50 h for HYFRG and 9.11 ± 1.45 and 6.75 ± 3.97 hours for RG, respectively. In conclusion, the administration of HYFRG resulted in a higher and faster absorption of compound K in both humans and rats compared to RG.

  11. Oral administration of d-limonene controls inflammation in rat colitis and displays anti-inflammatory properties as diet supplementation in humans.

    Science.gov (United States)

    d'Alessio, Patrizia A; Ostan, Rita; Bisson, Jean-François; Schulzke, Joerg D; Ursini, Matilde V; Béné, Marie C

    2013-07-10

    To further explore the anti-inflammatory properties of d-Limonene. A rat model was used to compare evolution of TNBS (2,5,6-trinitrobenzene sulfonic acid)-induced colitis after oral feeding with d-Limonene compared to ibuprofen. Peripheral levels of TNF-α (Tumor Necrosis Factor alpha) were assessed in all animals. Cell cultures of fibroblasts and enterocytes were used to test the effect of d-Limonene respectively on TNFα-induced NF-κB (nuclear factor-kappa B) translocation and epithelial resistance. Finally, plasmatic inflammatory markers were examined in an observational study of diet supplementation with d-Limonene-containing orange peel extract (OPE) in humans. Administered per os at a dose of 10mg/kg p.o., d-Limonene induced a significant reduction of intestinal inflammatory scores, comparable to that induced by ibuprofen. Moreover, d-Limonene-fed rats had significantly lowered serum concentrations of TNF-α compared to untreated TNBS-colitis rats. The anti-inflammatory effect of d-Limonene also involved inhibition of TNFα-induced NF-κB translocation in fibroblast cultures. The application of d-Limonene on colonic HT-29/B6 cell monolayers increased epithelial resistance. Finally, inflammatory markers, especially peripheral IL-6, markedly decreased upon OPE supplementation of elderly healthy subjects submitted or not to 56 days of dietary supplementation with OPE. In conclusion, d-Limonene indeed demonstrates significant anti-inflammatory effects both in vivo and in vitro. Protective effects on the epithelial barrier and decreased cytokines are involved, suggesting a beneficial role of d-Limonene as diet supplement in reducing inflammation. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Gene expression changes induced by ochratoxin A in renal and hepatic tissues of male F344 rat after oral repeated administration

    International Nuclear Information System (INIS)

    Arbillaga, Leire; Vettorazzi, Ariane; Gil, Ana G; Delft, Joost van; Garcia-Jalon, Jose Antonio; Lopez de Cerain, Adela

    2008-01-01

    Ochratoxin A (OTA), a naturally occurring mycotoxin, is nephrotoxic in all animal species tested and is considered a potent renal carcinogen, particularly in male rats. Its mechanism of toxicity is still unknown, although oxidative stress appears to be a plausible mechanism. Therefore, the objective of this study was to identify the biological pathways that are modulated in vivo by OTA in male F344 rats in order to gain further insight into its mechanism of renal toxicity. Rats were gavaged daily with OTA (500 μg/kg bw) and gene expression profiles in target and non-target organs were analyzed after 7 and 21 days administration. As was expected, a time-dependent increase of OTA concentrations was found in plasma, kidney and liver, with the concentrations found in both tissues being quite similar. However, histopathological examinations only revealed changes in kidney; signs of nephrotoxicity involving single cell necrosis and karyomegalic nuclei were observed in the treated rats. The number of differentially expressed genes in kidney was much higher than in liver (541 versus 11 at both time points). Several similarities were observed with other in vivo gene expression data. However, great differences were found with previous in vitro gene expression data, with the exception of DNA damage response which was not observed at mRNA level in any of our study conditions. Down-regulation was the predominant effect. Oxidative stress response pathway and genes involved in metabolism and transport were inhibited at both time points. RGN (regucalcin) - a gene implicated in calcium homeostasis - was strongly inhibited at both time points and genes implicated in cell survival and proliferation were up-regulated at day 21. Moreover, translation factors and annexin genes were up-regulated at both time points. Apart from oxidative stress, alterations of the calcium homeostasis and cytoskeleton structure may be present at the first events of OTA toxicity

  13. Simultaneous quantification of multiple components in rat plasma by UPLC-MS/MS and pharmacokinetic study after oral administration of Huangqi decoction.

    Science.gov (United States)

    Zeng, Jia-Kai; Li, Yuan-Yuan; Wang, Tian-Ming; Zhong, Jie; Wu, Jia-Sheng; Liu, Ping; Zhang, Hua; Ma, Yue-Ming

    2018-05-01

    A rapid, sensitive and accurate UPLC-MS/MS method was developed for the simultaneous quantification of components of Huangqi decoction (HQD), such as calycosin-7-O-β-d-glucoside, calycosin-glucuronide, liquiritin, formononetin-glucuronide, isoliquiritin, liquiritigenin, ononin, calycosin, isoliquiritigenin, formononetin, glycyrrhizic acid, astragaloside IV, cycloastragenol, and glycyrrhetinic acid, in rat plasma. After plasma samples were extracted by protein precipitation, chromatographic separation was performed with a C 18 column, using a gradient of methanol and 0.05% acetic acid containing 4mm ammonium acetate as the mobile phase. Multiple reaction monitoring scanning was performed to quantify the analytes, and the electrospray ion source polarity was switched between positive and negative modes in a single run of 10 min. Method validation showed that specificity, linearity, accuracy, precision, extraction recovery, matrix effect and stability for 14 components met the requirements for their quantitation in biological samples. The established method was successfully applied to the pharmacokinetic study of multiple components in rats after intragastric administration of HQD. The results clarified the pharmacokinetic characteristics of multiple components found in HQD. This research provides useful information for understanding the relation between the chemical components of HQD and their therapeutic effects. Copyright © 2017 John Wiley & Sons, Ltd.

  14. An improved technique for oral administration of solutions of test ...

    African Journals Online (AJOL)

    Medicut intravenous cannula as an improvised oral cannula to administer solutions of drugs and test substances to experimental rats. Techniques of handling and manipulating the rat with the goal of having the eosophagus as straight as possible ...

  15. Effects of 6 weeks oral administration of Phyllanthus acidus leaf water extract on the vascular functions of middle-aged male rats.

    Science.gov (United States)

    Chongsa, Watchara; Kanokwiroon, Kanyanatt; Jansakul, Chaweewan

    2015-12-24

    Leaves of Phyllanthus acidus (PA) have been used in Thai traditional medicine for the treatment of hypertension. We have previously shown that chronic treatment of a PA water extract to middle-aged male rats caused a lowering of the body and serum lipids, two of the parameters that are implicated in cardiovascular disease. To investigate if chronic treatment of middle-aged male rats with a PA water extract affected the perivascular (aortic) adipose tissue (PVAT) and/or their vascular functions Fresh leaves of PA were extracted with water and orally gavaged to the middle-aged male rats for 6 weeks. Vascular functions were studied in vitro using isolated thoracic aorta with and without PVAT, and mesenteric rings in Krebs Heinseleit solution with results recorded with a Polygraph or a Myograph system. The amount of blood vessel eNOS and CSE (cystathionine-γ-lyase) expression was measured by Western blotting. PA treatment caused a lower maximal contractile response to phenylephrine (Phe) of the endothelium-intact aortic ring than that of the control group. This effect was abolished by N(G)-nitro-l-arginine (l-NA) or by denudation of the endothelium. dl-propargylglycine (PAG, H2S inhibitor) and TEA (Ca(2+)-activated K(+) channel blocker), but not glybenclamide (ATP-activated K(+) channel blocker), caused a similar increase in the baseline of the endothelium-intact aortic ring in the presence of l-NA in both the PA-treated and control aortic rings. This effect sequentially resulted in a greater contractile response of the aortic rings of both groups to Phe. Glybenclamide also caused a similar increase in the maximal contraction of the endothelium-intact blood vessels with l-NA to both groups. PAG, TEA or glybenclamide did not modify the phenylephrine C-R curves for either group of the PVAT-endothelium-intact aortic rings preincubated with l-NA. The CSE levels of the thoracic aorta and at the PVAT were not different between the PA-treated and the control group

  16. Determination and Pharmacokinetic Study of Gentiopicroside, Geniposide, Baicalin, and Swertiamarin in Chinese Herbal Formulae after Oral Administration in Rats by LC-MS/MS

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    Chia-Ming Lu

    2014-12-01

    Full Text Available A sensitive and efficient liquid chromatography-tandem mass spectrometry (LC-MS/MS method was developed for the simultaneous determination of gentiopicroside, geniposide, baicalin, and swertiamarin in rat plasma. To avoid the stress caused by restraint or anesthesia, a freely moving rat model was used to investigate the pharmacokinetics of herbal medicine after the administration of a traditional Chinese herbal prescription of Long-Dan-Xie-Gan-Tang (10 g/kg, p.o.. Analytes were separated by a C18 column with a gradient system of methanol–water containing 1 mM ammonium acetate with 0.1% formic acid. The linear ranges were 10–500 ng/mL for gentiopicroside, geniposide, and baicalin, and 5–250 ng/mL for swertiamarin in biological samples. The intra- and inter-day precision (relative standard deviation ranged from 0.9% to 11.4% and 0.3% to 14.4%, respectively. The accuracy (relative error was from −6.3% to 10.1% at all quality control levels. The analytical system provided adequate matrix effect and recovery with good precision and accuracy. The pharmacokinetic data demonstrated that the area under concentration-time curve (AUC values of gentiopicroside, geniposide, baicalin, and swertiamarin were 1417 ± 83.8, 302 ± 25.8, 753 ± 86.2, and 2.5 ± 0.1 min µg/mL. The pharmacokinetic profiles provide constructive information for the dosage regimen of herbal medicine and also contribute to elucidate the absorption mechanism in herbal applications and pharmacological experiments.

  17. HPLC–MS and HPLC–MS/MS analysis of seven active constituents of Xiao-Xu-Ming decoction and application to a pharmacokinetic study after oral administration to rat

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    Yilin Wang

    2012-04-01

    Full Text Available Xiao-xu-ming decoction (XXMD is a traditional Chinese medicine that has been widely used to treat theoplegia and its sequelae. This paper reports the development of three separate assays based on reversed phase high-performance liquid chromatography–mass spectrometry (HPLC–MS and HPLC–MS/MS for the determination of seven active constituents of XXMD viz oroxylin A-7-O-glucuronide, wogonoside, liquiritigenin, cimifugin, 5-O-methylvisammiol, glycyrrhizic acid and glycyrrhetinic acid in rat plasma. All calibration curves were linear (r >0.99 with lower limits of quantitation (LLOQs<12.4 ng/mL. Intra- and inter-day precisions (as relative standard deviation were all <10.7% with recoveries in the range of 88.7–113%. In addition, the seven analytes were shown to be stable in rat plasma samples under relevant storage conditions. The validated methods were successfully applied to a pharmacokinetic study in rat after oral administration of XXMD.

  18. Reversing gastric mucosal alterations during ethanol-induced chronic gastritis in rats by oral administration of Opuntia ficus-indica mucilage

    Science.gov (United States)

    Vázquez-Ramírez, Ricardo; Olguín-Martínez, Marisela; Kubli-Garfias, Carlos; Hernández-Muñoz, Rolando

    2006-01-01

    AIM: To study the effect of mucilage obtained from cladodes of Opuntia ficus-indica (Cactaceae) on the healing of ethanol-induced gastritis in rats. METHODS: Chronic gastric mucosa injury was treated with mucilage (5 mg/kg per day) after it was induced by ethanol. Lipid composition, activity of 5’-nucleotidase (a membrane-associated ectoenzyme) and cytosolic activities of lactate and alcohol dehydrogenases in the plasma membrane of gastric mucosa were determined. Histological studies of gastric samples from the experimental groups were included. RESULTS: Ethanol elicited the histological profile of gastritis characterized by loss of the surface epithelium and infiltration of polymorphonuclear leukocytes. Phosphatidylcholine (PC) decreased and cholesterol content increased in plasma membranes of the gastric mucosa. In addition, cytosolic activity increased while the activity of alcohol dehydrogenases decreased. The administration of mucilage promptly corrected these enzymatic changes. In fact, mucilage readily accelerated restoration of the ethanol-induced histological alterations and the disturbances in plasma membranes of gastric mucosa, showing a univocal anti-inflammatory effect. The activity of 5’-nucleotidase correlated with the changes in lipid composition and the fluidity of gastric mucosal plasma membranes. CONCLUSION: The beneficial action of mucilage seems correlated with stabilization of plasma membranes of damaged gastric mucosa. Molecular interactions between mucilage monosaccharides and membrane phospholipids, mainly PC and phosphatidylethanolamine (PE), may be the relevant features responsible for changing activities of membrane-attached proteins during the healing process after chronic gastric mucosal damage. PMID:16865772

  19. Reversing gastric mucosal alterations during ethanol-induced chronic gastritis in rats by oral administration of Opuntia ficus-indica mucilage.

    Science.gov (United States)

    Vázquez-Ramírez, Ricardo; Olguín-Martínez, Marisela; Kubli-Garfias, Carlos; Hernández-Muñoz, Rolando

    2006-07-21

    To study the effect of mucilage obtained from cladodes of Opuntia ficus-indica (Cactaceae) on the healing of ethanol-induced gastritis in rats. Chronic gastric mucosa injury was treated with mucilage (5 mg/kg per day) after it was induced by ethanol. Lipid composition, activity of 5'-nucleotidase (a membrane-associated ectoenzyme) and cytosolic activities of lactate and alcohol dehydrogenases in the plasma membrane of gastric mucosa were determined. Histological studies of gastric samples from the experimental groups were included. Ethanol elicited the histological profile of gastritis characterized by loss of the surface epithelium and infiltration of polymorphonuclear leukocytes. Phosphatidylcholine (PC) decreased and cholesterol content increased in plasma membranes of the gastric mucosa. In addition, cytosolic activity increased while the activity of alcohol dehydrogenases decreased. The administration of mucilage promptly corrected these enzymatic changes. In fact, mucilage readily accelerated restoration of the ethanol-induced histological alterations and the disturbances in plasma membranes of gastric mucosa, showing a univocal anti-inflammatory effect. The activity of 5'-nucleotidase correlated with the changes in lipid composition and the fluidity of gastric mucosal plasma membranes. The beneficial action of mucilage seems correlated with stabilization of plasma membranes of damaged gastric mucosa. Molecular interactions between mucilage monosaccharides and membrane phospholipids, mainly PC and phosphatidylethanolamine (PE), may be the relevant features responsible for changing activities of membrane-attached proteins during the healing process after chronic gastric mucosal damage.

  20. Oral administration of drugs with hypersensitivity potential induces germinal center hyperplasia in secondary lymphoid organ/tissue in Brown Norway rats, and this histological lesion is a promising candidate as a predictive biomarker for drug hypersensitivity occurrence in humans

    International Nuclear Information System (INIS)

    Tamura, Akitoshi; Miyawaki, Izuru; Yamada, Toru; Kimura, Juki; Funabashi, Hitoshi

    2013-01-01

    It is important to evaluate the potential of drug hypersensitivity as well as other adverse effects during the preclinical stage of the drug development process, but validated methods are not available yet. In the present study we examined whether it would be possible to develop a new predictive model of drug hypersensitivity using Brown Norway (BN) rats. As representative drugs with hypersensitivity potential in humans, phenytoin (PHT), carbamazepine (CBZ), amoxicillin (AMX), and sulfamethoxazole (SMX) were orally administered to BN rats for 28 days to investigate their effects on these animals by examinations including observation of clinical signs, hematology, determination of serum IgE levels, histology, and flow cytometric analysis. Skin rashes were not observed in any animals treated with these drugs. Increases in the number of circulating inflammatory cells and serum IgE level did not necessarily occur in the animals treated with these drugs. However, histological examination revealed that germinal center hyperplasia was commonly induced in secondary lymphoid organs/tissues in the animals treated with these drugs. In cytometric analysis, changes in proportions of lymphocyte subsets were noted in the spleen of the animals treated with PHT or CBZ during the early period of administration. The results indicated that the potential of drug hypersensitivity was identified in BN rat by performing histological examination of secondary lymphoid organs/tissues. Data obtained herein suggested that drugs with hypersensitivity potential in humans gained immune reactivity in BN rat, and the germinal center hyperplasia induced by administration of these drugs may serve as a predictive biomarker for drug hypersensitivity occurrence. - Highlights: • We tested Brown Norway rats as a candidate model for predicting drug hypersensitivity. • The allergic drugs did not induce skin rash, whereas D-penicillamine did so in the rats. • Some of allergic drugs increased

  1. Oral administration of drugs with hypersensitivity potential induces germinal center hyperplasia in secondary lymphoid organ/tissue in Brown Norway rats, and this histological lesion is a promising candidate as a predictive biomarker for drug hypersensitivity occurrence in humans

    Energy Technology Data Exchange (ETDEWEB)

    Tamura, Akitoshi, E-mail: akitoshi-tamura@ds-pharma.co.jp; Miyawaki, Izuru; Yamada, Toru; Kimura, Juki; Funabashi, Hitoshi

    2013-08-15

    It is important to evaluate the potential of drug hypersensitivity as well as other adverse effects during the preclinical stage of the drug development process, but validated methods are not available yet. In the present study we examined whether it would be possible to develop a new predictive model of drug hypersensitivity using Brown Norway (BN) rats. As representative drugs with hypersensitivity potential in humans, phenytoin (PHT), carbamazepine (CBZ), amoxicillin (AMX), and sulfamethoxazole (SMX) were orally administered to BN rats for 28 days to investigate their effects on these animals by examinations including observation of clinical signs, hematology, determination of serum IgE levels, histology, and flow cytometric analysis. Skin rashes were not observed in any animals treated with these drugs. Increases in the number of circulating inflammatory cells and serum IgE level did not necessarily occur in the animals treated with these drugs. However, histological examination revealed that germinal center hyperplasia was commonly induced in secondary lymphoid organs/tissues in the animals treated with these drugs. In cytometric analysis, changes in proportions of lymphocyte subsets were noted in the spleen of the animals treated with PHT or CBZ during the early period of administration. The results indicated that the potential of drug hypersensitivity was identified in BN rat by performing histological examination of secondary lymphoid organs/tissues. Data obtained herein suggested that drugs with hypersensitivity potential in humans gained immune reactivity in BN rat, and the germinal center hyperplasia induced by administration of these drugs may serve as a predictive biomarker for drug hypersensitivity occurrence. - Highlights: • We tested Brown Norway rats as a candidate model for predicting drug hypersensitivity. • The allergic drugs did not induce skin rash, whereas D-penicillamine did so in the rats. • Some of allergic drugs increased

  2. Hematological Parameters and the State of Liver Cells of Rats After Oral Administration of Aflatoxin B1 Alone and Together with Nanodiamonds

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    Baron AV

    2010-01-01

    Full Text Available Abstract Hematological parameters and the state of liver cells of rats were examined in vivo after the animals received aflatoxin B1 (AfB1 alone and together with modified nanodiamonds (MND synthesized by detonation. The rats that had received the MND hydrosol had elevated leukocyte levels, mainly due to higher granulocyte counts and somewhat increased monocyte counts compared to control rats. Hematological parameters of the rats that had received AfB1 alone differed from those of the control rats in another way: total white blood cell counts were significantly lower due to the decreased lymphocyte counts. In rats that had consumed AfB1 with the MND hydrosol, changes in hematological parameters were less pronounced than in rats that had consumed either AfB1 or MND. Electron microscopy showed that hepatocytes of the rats that had received the MND hydrosol or AfB1 with the MND hydrosol contained elevated levels of lipid inclusions and lysosomes. Hyperplasia of the smooth endoplasmic reticulum (EPR was revealed in liver specimens of the rats that had received AfB1. Results of the study suggest the conclusion about mutual mitigation of the effects of nanoparticles and the mycotoxin on rats blood and liver cells after AfB1 has adsorbed on MND.

  3. Identification of metabolites in human and rat urine after oral administration of Xiao-Qing-Long-Tang granule using ultra high performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry.

    Science.gov (United States)

    Zhou, Lei; Zhang, Qiang; Qi, Wen; Yan, Shuai; Qu, Jialin; Makino, Toshiaki; Yuan, Dan

    2017-09-01

    Xiao-Qing-Long-Tang is a traditional Chinese formula used for the treatment of cold syndrome, bronchitis, and nasal allergies for thousands of years. However, the in vivo integrated metabolism of its multiple components and the active chemical constituents of Xiao-Qing-Long-Tang remain unknown. In this study, a method using ultra high performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry was established for the detection and identification of the metabolites in human and rat urine after oral administration of Xiao-Qing-Long-Tang. A total of 19 compounds were detected or tentatively identified in human urine samples, including eight prototypes and 11 metabolites. Also, a total of 50 compounds were detected or tentatively identified in rat urine samples, including 15 prototypes and 35 metabolites detected with either a highly sensitive extracted ion chromatogram method or the MS E determination using Mass Fragment software. Our results indicated that phase Ⅱ reactions (e.g. glucuronidation and sulfation) were the main metabolic pathways of flavones, while phase I reactions (e.g. demethylation and hydroxylation) were the major metabolic reaction for alkaloids, lignans, and ginger essential oil. This investigation provided important structural information on the metabolism of Xiao-Qing-Long-Tang and provided evidence to obtain a more comprehensive metabolic profile. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Simultaneous quantitation of polygalaxanthone III and four ginsenosides by ultra-fast liquid chromatography with tandem mass spectrometry in rat and beagle dog plasma after oral administration of Kai-Xin-San: application to a comparative pharmacokinetic study.

    Science.gov (United States)

    Lv, Chunxiao; Li, Qing; Zhang, Xiaowen; He, Bosai; Xu, Huarong; Yin, Yidi; Liu, Ran; Liu, Jingjing; Chen, Xiaohui; Bi, Kaishun

    2014-05-01

    A fast, selective, and quantitative ultra-fast liquid chromatography with tandem mass spectrometry method has been developed and validated for the simultaneous quantitation of polygalaxanthone III, ginsenoside Rb1, ginsenoside Rd, ginsenoside Re, and ginsenoside Rg1 in the plasma of rat and beagle dog after oral administration of Kai-Xin-San. After addition of the internal standard, salidroside, the plasma samples were extracted by liquid-liquid extraction and separated on a Venusil MP C18 column with methanol/0.01% acetic acid water as mobile phase. The tandem mass spectrometric detection was performed in the multiple reaction monitoring with turbo ion spray source in a switching ionization mode. The method was examined, and found to be precise and accurate with the linearity range of the compounds. The intra- and interday precision and accuracy of the analytes were well within acceptance criteria (±15%). The mean extraction recoveries of analytes and internal standard were all >75.0%. The validated method has been successfully applied to comparing pharmacokinetic profiles of analytes in rat and beagle dog plasma. The results indicated that no significant differences were observed in pharmacokinetic parameters of ginsenoside Rg1, while the others had significant differences, which may due to the different mechanisms of absorption and metabolism. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Simultaneous determination of phenolic acids and diterpenoids and their comparative pharmacokinetic study in normal and acute blood stasis rats by UFLC-MS/MS after oral administration of Guan-Xin-Shu-Tong capsules.

    Science.gov (United States)

    Gao, Xun; Mu, Jingqing; Guan, Shaoyi; Li, Qing; Du, Yiyang; Zhang, Huifen; Bi, Kaishun

    2018-01-01

    Guan-Xin-Shu-Tong capsules are one of the well-known and first-line Chinese traditional herbal formula for treating coronary heart disease. A validated and sensitive method via ultra fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) was established to simultaneously determinate five phenolic acids and four diterpenoids in rats in order to investigate their pharmacokinetic profiles firstly. Analytes were extracted by ethyl acetate and determined via multiple reaction monitoring mode in both positive and negative ion modes. The values for limit of quantification were in range of 0.025-1.250ng/ml. Inter- and intra-day precisions were no more than 10.9% with accuracy of -11.0%-10.6%, meanwhile the stable and suitable extraction recoveries were also obtained. And finally such excellent method was used to compare the pharmacokinetics of nine compounds in normal and acute blood stasis rats after oral administration of Guan-Xin-Shu-Tong capsules. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Simultaneous Determination of Purpurin, Munjistin and Mollugin in Rat Plasma by Ultra High Performance Liquid Chromatography-Tandem Mass Spectrometry: Application to a Pharmacokinetic Study after Oral Administration of Rubia cordifolia L. Extract

    Directory of Open Access Journals (Sweden)

    Mingjie Gao

    2016-06-01

    Full Text Available A specific, simple, sensitive Ultra High Performance Liquid Chromatography-tandem Mass Spectrometry (UHPLC-MS/MS method has been developed and validated for the simultaneous determination and pharmacokinetic study of purpurin, munjistin, and mollugin in rat plasma. Chromatographic separation was carried out using a C18 column (ACQUITY UPLC® HSS T3, 1.8 μm, 2.1 × 100 mm with gradient elution. The compounds were detected on a 6430 triple-quadrupole tandem MS with an electrospray ionization (ESI interface using multiple reaction monitoring (MRM in positive ionization mode. The samples were prepared by a liquid-liquid extraction (LLE method with ethyl acetate after being spiked with an internal standard (bifendate. The current UHPLC-MS/MS assay was validated for its linearity, intra-day and inter-day precisions, accuracy, extraction recovery, matrix effect and stability in different conditions. The method was linear for all analytes over the investigated range with all determined correlation coefficients exceeding 0.9900. The intra-day and inter-day precisions were in the range of 4.21% to 14.84%, and the relative errors of accuracies were in the range of −14.05% to 14.75%. The mean recoveries and matrix effects of purpurin, munjistin, and mollugin were higher than 78.87% and 92.56%, repectively. After oral administration of 0.82 g/kg of Rubia cordifolia extract, the maximum plasma concentrations (Cmax were 70.10 ± 11.78 ng/mL for purpurin, 26.09 ± 6.6 ng/mL for munjistin, and 52.10 ± 6.71 ng/mL for mollugin. The time for maximal concentration (Tmax was 1.61 ± 0.24 h for purpurin, 2.58 ± 0.19 h for munjistin, and 1.99 ± 0.21 h for mollugin. The established method was further applied to a pharmacokinetic study of purpurin, munjistin, and mollugin in rat plasma. It was concluded from the pharmacokinetic parameters that the three analytes showed a process of slow absorption and metabolism after oral administration of R. cordifolia extract to

  7. Intravenous alcohol self-administration in the P rat.

    Science.gov (United States)

    Windisch, Kyle A; Kosobud, Ann E K; Czachowski, Cristine L

    2014-08-01

    Alcohol consumption produces a complex array of effects that can be divided into two types: the explicit pharmacological effects of ethanol (which can be temporally separate from time of intake) and the more temporally "relevant" effects (primarily olfactory and taste) that bridge the time from intake to onset of the pharmacological effects. Intravenous (IV) self-administration of ethanol limits the confounding "non-pharmacological" effects associated with oral consumption, allows for controlled and precise dosing, and bypasses first order absorption kinetics, allowing for more direct and better-controlled assessment of alcohol's effect on the brain. IV ethanol self-administration has been reliably demonstrated in mouse and human experimental models; however, models of IV self-administration have been historically problematic in the rat. An operant multiple-schedule study design was used to elucidate the role of each component of a compound IV-ethanol plus oral-sucrose reinforcer. Male alcohol-preferring P rats had free access to both food and water during all IV self-administration sessions. Animals were trained to press a lever for orally delivered 1% sucrose (1S) on a fixed ratio 4 schedule, and then surgically implanted with an indwelling jugular catheter. Animals were then trained to respond on a multiple FR4-FR4 schedule composed of alternating 2.5-min components across 30-min sessions. For the multiple schedule, two components were used: an oral 1S only and an oral 1S plus IV 20% ethanol (25 mg/kg/injection). Average total ethanol intake was 0.47 ± 0.04 g/kg. We found significantly higher earning of sucrose-only reinforcers and greater sucrose-lever error responding relative to the compound oral-sucrose plus IV-ethanol reinforcer. These response patterns suggest that sucrose, not ethanol, was responsible for driving overall responding. The work with a compound IV ethanol-oral sucrose reinforcer presented here suggests that the existing intravenous ethanol

  8. Distribution of 14C after oral administration of [1-14C]linoleic acid in rats fed different levels of essential fatty acids

    International Nuclear Information System (INIS)

    Becker, W.

    1984-01-01

    Rats from an inbred Sprague-Dawley strain were fed semisynthetic diets with a low [0.3 energy percent (en %)], normal (3 en %) or high (10 en %) content of essential fatty acids (EFA) for at least three generations. Twenty-nine- to 33-day-old male rats were given a single intragastric dose of [1-14C]linoleic acid in olive oil, and the respiratory CO2, urine and feces were collected for 46 hours (expt 1) or 20 hours (expt 2). The 14C activity in respiratory CO2, feces, urine and the carcass was determined in both experiments. In experiment 2 it was also measured in samples of the brown fat, liver, adrenals, white fat, skeletal muscles and brain. In both experiments the rats fed the low EFA diet retained significantly more 14C activity than the rats fed the normal or high EFA diets. In all groups the concentration of label was highest in the brown fat and the adrenals, but the above differences among the groups with respect to 14C retention were mainly observed in the liver, skeletal muscles and brain

  9. effect of oral administration of aqueous extract of cassia occidentalis

    African Journals Online (AJOL)

    DR. AMINU

    seeds extract's relation with acid – base balance of the body. Serum concentrations ... Oral administration of aqueous extract of C. occidentalis ... irrespective of duration of administration (weeks). .... Student 't' test was used to analyse the data.

  10. Unraveling the Rat Intestine, Spleen and Liver Genome-Wide Transcriptome after the Oral Administration of Lavender Oil by a Two-Color Dye-Swap DNA Microarray Approach

    OpenAIRE

    Kubo, Hiroko; Shibato, Junko; Saito, Tomomi; Ogawa, Tetsuo; Rakwal, Randeep; Shioda, Seiji

    2015-01-01

    The use of lavender oil (LO) – a commonly, used oil in aromatherapy, with well-defined volatile components linalool and linalyl acetate – in non-traditional medicine is increasing globally. To understand and demonstrate the potential positive effects of LO on the body, we have established an animal model in this current study, investigating the orally administered LO effects genome wide in the rat small intestine, spleen, and liver. The rats were administered LO at 5 mg/kg (usual therapeutic ...

  11. HTO oral administration in mice: Pt. 1

    International Nuclear Information System (INIS)

    Yamamoto, O.; Yokoro, K.; Seyama, T.; Kinomura, A.; Nomura, T.

    1990-01-01

    Tritiated water in various concentrations was orally administered continuously to (C57BL/6N and C3H/He)F 1 female mice in a closed animal chamber. Tritium radioactivity in various organ tissues was measured periodically after initiating tritiated water intake using an automatic sample combustion system and a liquid scintillation counter. After 7 days the specific radioactivity reached a plateau. Within a range of 1.48 x 10 11 to 5.92 x 10 11 Bq/dm 3 as the concentration of tritiated water in drinking water, the time of death after initiating the administration was about 2 weeks, a typical time for haematopoietic death. A linear relationship of times of death with tritiated water concentrations in drinking water was observed, on a log-log scale, between 1.85 x 10 10 Bq/dm 3 and 1.48 x 10 11 Bq/dm 3 . At concentrations lower than 9.25 x 10 9 Bq/dm 3 , mice no longer died from haematopoietic failure. The authors conclude, therefore, that there should be a threshold dose rate for haematopoietic death. (author)

  12. Elucidation of Arctigenin Pharmacokinetics and Tissue Distribution after Intravenous, Oral, Hypodermic and Sublingual Administration in Rats and Beagle Dogs: Integration of In Vitro and In Vivo Findings

    OpenAIRE

    Jie Li; Jie Li; Jie Li; Xin Li; Xin Li; Xin Li; Yu-Shan Ren; Yu-Shan Ren; Yuan-Yuan Lv; Yuan-Yuan Lv; Yuan-Yuan Lv; Jun-Sheng Zhang; Jun-Sheng Zhang; Jun-Sheng Zhang; Xiao-Li Xu

    2017-01-01

    Although arctigenin (AG) has diverse bioactivities, such as anti-oxidant, anti-inflammatory, anti-cancer, immunoregulatory and neuroprotective activities, its pharmacokinetics have not been systematically evaluated. The purpose of this work was to identify the pharmacokinetic properties of AG via various experiments in vivo and in vitro. In this research, rats and beagle dogs were used to investigate the PK (pharmacokinetics, PK) profiles of AG with different drug-delivery manners, including ...

  13. Intracerebroventricular administration of taurine impairs learning and memory in rats.

    Science.gov (United States)

    Ito, Koichi; Arko, Matevž; Kawaguchi, Tomohiro; Kikusui, Takefumi; Kuwahara, Masayoshi; Tsubone, Hirokazu

    2012-03-01

    Taurine is a semi-essential amino acid widely distributed in the body and we take in it from a wide range of nutritive-tonic drinks to improve health. To date, we have elucidated that oral supplementation of taurine does not affect learning and memory in the rat. However, there are few studies concerning the direct effects of taurine in the brain at the behavior level. In this study, we intracerebroventricularly administered taurine to rats and aimed to elucidate the acute effects on learning and memory using the Morris water maze method. Escape latency, swim distance, and distance to zone, which is the integral of the distance between the rats and the platform for every 0.16 seconds, were adopted as parameters of the ability of learning and memory. We also tried to evaluate the effect of intraperitoneal taurine administration. Escape latency, swim distance, and distance to zone were significantly longer in the intracerebroventricularly taurine-administered rats than in the saline-administered rats. Mean swimming velocity was comparable between these two groups, although the physical performance was improved by taurine administration. Probe trials showed that the manner of the rats in finding the platform was comparable. In contrast, no significant differences were found between the intraperitoneally taurine-administered rats and the saline-administered rats. These results indicate that taurine administered directly into the brain ventricle suppresses and delays the ability of learning and memory in rats. In contrast, it is implied that taurine administered peripherally was not involved in learning and memory.

  14. Metabolism, oral bioavailability and pharmacokinetics of chemopreventive kaempferol in rats

    Science.gov (United States)

    Barve, Avantika; Chen, Chi; Hebbar, Vidya; Desiderio, Joseph; Saw, Constance Lay-Lay; Kong, Ah-Ng

    2012-01-01

    The purpose of this study was to compare the hepatic and small intestinal metabolism, and examine bioavailability and gastro-intestinal first-pass effects of Kaempferol in the rats. Liver and small intestinal microsomes fortified with either NADPH or UDPGA were incubated with varying concentrations of Kaempferol for upto 120 minutes. Based on the values of the kinetic constants (Km and Vmax), the propensity for UDPGA-dependent conjugation as compared to NADPH-dependent oxidative metabolism was higher for both hepatic and small intestinal microsomes. Male Sprague-Dawley rats were administered Kaempferol intravenously (IV) (10, 25 mg/kg) or orally (100, 250 mg/kg). Gastro-intestinal first pass effects were observed by collecting portal blood after oral administration of 100 mg/kg Kaempferol. Pharmacokinetic parameters were obtained by Noncompartmental analysis using WinNonlin. After IV administration, the plasma concentration-time profiles for 10 and 25 mg/kg were consistent with high clearance (~ 3 L/hr/kg) and large volumes of distribution (8-12 L/kg). The disposition was characterized by a terminal half-life value of 3-4 hours. After oral administration the plasma concentration-time profiles demonstrated fairly rapid absorption (tmax ~ 1-2 hours). The area under the curve (AUC) values after IV and oral doses increased proportional to the dose. The bioavailability (F) was poor at ~ 2%. Analysis of portal plasma after oral administration revealed low to moderate absorption. Taken together, the low F of Kaempferol is attributed in part to extensive first-pass metabolism by glucuronidation and other metabolic pathways in the gut and in the liver. PMID:19722166

  15. Biological fate of a single administration of 191Pt in rats following different routes of exposure

    International Nuclear Information System (INIS)

    Moore, W. Jr.; Hysell, D.; Crocker, W.; Stara, J.

    1975-01-01

    The retention, tissue distribution, and excretion of 191 Pt in adult rats was determined following oral, intravenous (IV), and intratracheal administration. The highest retention was obtained following IV dosing, and lowest retention (less than 0.5 percent) occurred after oral dosing. Tissues containing the highest concentrations of 191 Pt following IV administration were the kidney, adrenal, spleen, and liver. Following a single oral dose, almost all of the 191 Pt was excreted in the feces due to nonabsorption, whereas after IV dosing, similar quantities were excreted in both the urine and feces. Following IV dosing of pregnant rats, 191 Pt was found in all the fetuses; however, the amount was small

  16. Comparatively evaluating the pharmacokinetic of fifteen constituents in normal and blood deficiency rats after oral administration of Xin-Sheng-Hua Granule by UPLC-MS/MS.

    Science.gov (United States)

    Pang, Han-Qing; Tang, Yu-Ping; Cao, Yu-Jie; Tan, Ya-Jie; Jin, Yi; Shi, Xu-Qin; Huang, Sheng-Liang; Sun, Da-Zheng; Sun, Jin; Tang, Zhi-Shu; Duan, Jin-Ao

    2017-09-01

    Xin-Sheng-Hua Granule (XSHG), a famous traditional Chinese medicine prescription, are clinically applied for the treatment of postpartum disease through nourishing blood and promoting blood circulation. In this investigation, a multi-constituents (trigonelline, stachydrine hydrochloride, hydroxysafflor yellow A, chlorogenic acid, amygdalin, leonurine, liquiritin, ferulic acid, senkyunolide I, senkyunolide H, glycyrrhizic acid, senkyunolide A, ligustilide, butylidenephthalide and glycyrrhetinic acid) pharmacokinetic study of XSHG was conducted for the first time. These fifteen constituents in both normal and blood deficiency rat plasma were monitored by using the established and validated ultra-high-performance liquid chromatography coupled with a triple quadrupole electrospray tandem mass spectrometry (UPLC-TQ-MS/MS) method. The samples were prepared through removing protein from plasma with three volumes of methanol. Sufficient separation of target constituents and internal standards (chloramphenicol and clarithromycin) was obtained on a Thermo Scientific Hypersil GOLD column (100mm×3mm, 1.9μm) within a 20min gradient elution (0.1% formic acid aqueous - acetonitrile). Multiple reaction monitoring (MRM) mode was applied to monitor target analytes in both positive and negative electrospray ionization. For the fifteen selected target analytes, this method was fully validated with excellent linearity (r≥0.9925), satisfactory intra- and inter-day precisions (RSD≤11.87%), as well as good accuracies (RE, between -12.84 and 11.69). And the stabilities, matrix effects and extraction recoveries of the rat plasma samples were also within acceptable limits (RSD<15%). Compared to normal group, the pharmacokinetics of major active constituents (except liquiritin and glycyrrhetinic acid) had significant differences (P<0.05) in the model rats, indicated that several metabolite enzymes activities could be altered at disease condition. Copyright © 2017 Elsevier B.V. All

  17. A HILIC-UHPLC-MS/MS untargeted urinary metabonomics combined with quantitative analysis of five polar biomarkers on osteoporosis rats after oral administration of Gushudan.

    Science.gov (United States)

    Wu, Xiao; Huang, Yue; Sun, Jinghan; Wen, Yongqing; Qin, Feng; Zhao, Longshan; Xiong, Zhili

    2018-01-01

    A HILIC-UHPLC-MS/MS untargeted urinary metabonomic method combined with quantitative analysis of five potential polar biomarkers in rat urine was developed and validated, to further understand the anti-osteoporosis effect of Gushudan(GSD) and its mechanism on prednisolone-induced osteoporosis(OP) rats in this study. The metabolites were separated and identified on Waters BEH HILIC (2.1mm×100mm, 1.7μm) column using the Waters ACQUITY™ ultra performance liquid chromatography system (Waters Corporation, Milford, USA) coupled with a Micromass Quattro Micro™ API mass spectrometer (Waters Corp, Milford, MA, USA). Principal component analysis (PCA) was used to identify potential biomarkers. Primary potential polar biomarkers including creatinine, taurine, betaine, hypoxanthine and cytosine, which were related to energy metabolism, lipid metabolism and amino acid metabolism, were found in the untargeted metabonomic research. Moreover, these targeted biomarkers were further separated and quantified in multiple-reaction monitoring (MRM) with positive ionization mode, using tinidazole as internal standard (I.S.). Good linearities (r>0.99) were obtained for all the analytes with the low limit of quantification from 1.00 to 12.8μg/mL. The relative standard deviation (RSD) of the intra-day and inter-day precisions were within 15.0% and the accuracy ranged from -14.3% to 13.5%. The recovery was more than 85.0%. And the validated method was successfully applied to investigate the urine samples of the control group, prednisolone-induced osteoporosis model group and Gushudan-treatment group in rats. Compared to the control group, the level of creatinine, taurine, betaine, hypoxanthine and cytosine in the model group revealed a significant decrease trend (p<0.05), while the Gushudan-treatment group showed no statistically differences by an independent sample t-test. This paper provided a better understanding of the therapeutic effect and mechanism of GSD on prednisolone

  18. Characterization of metabolites of leonurine (SCM-198) in rats after oral administration by liquid chromatography/tandem mass spectrometry and NMR spectrometry.

    Science.gov (United States)

    Zhu, Qing; Zhang, Jinlian; Yang, Ping; Tan, Bo; Liu, Xinhua; Zheng, Yuanting; Cai, Weimin; Zhu, Yizhun

    2014-01-01

    Leonurine, a major bioactive component from Herba Leonuri, shows therapeutic potential for cardiovascular disease and stroke prevention in some preclinical experiments. The aim of this study is to characterize metabolites of leonurine in rats using high performance liquid chromatography coupled with tandem mass spectrometry (HPLC/MS/MS). The chromatographic separation was performed on an Agilent ZORBAX SB-C18 column using a gradient elution with acetonitrile/ammonium acetate buffer (10 mM, pH 4.0) solvent system. An information dependent acquisition (IDA) method was developed for screening and identifying metabolites of leonurine under positive ion mode. Compared with control, the interesting compound in the extracted ion chromatogram (XIC) of the in vivo samples was chosen and further identified by analyzing their retention times, changes in observed mass (Δm/z), and spectral patterns of product ion utilizing advanced software tool. For the first time, a total of three metabolites were identified, including two phase II metabolites generated by glucuronidation (M1) and sulfation (M2) and one phase I metabolite formed by O-demethylation (M3). Finally, the lead metabolite M1 was isolated from urine and its structure was characterized as leonurine-10-O- β-D-glucuronide by NMR spectroscopy (¹H, ¹³C, HMBC, and HSQC).

  19. Oral iron administration in suckling piglets – a review

    Directory of Open Access Journals (Sweden)

    Martin Svoboda

    2018-01-01

    Full Text Available Iron deficiency is presently a serious problem in suckling piglets on pig farms. The most often used method of anaemia prevention in piglets is parenteral administration of iron dextran. Oral iron represents an alternative to this method. The goal of this article is to review current knowledge on oral iron administration in suckling piglets. The substances that can be used for this purpose include iron dextran, iron salts, iron chelates, carbonyl iron, an iron polymaltose complex and iron microparticles. The different methods of oral iron administration in piglets are discussed.

  20. Repeated administration of fresh garlic increases memory retention in rats.

    Science.gov (United States)

    Haider, Saida; Naz, Nosheen; Khaliq, Saima; Perveen, Tahira; Haleem, Darakhshan J

    2008-12-01

    Garlic (Allium sativum) is regarded as both a food and a medicinal herb. Increasing attention has focused on the biological functions and health benefits of garlic as a potentially major dietary component. Chronic garlic administration has been shown to enhance memory function. Evidence also shows that garlic administration in rats affects brain serotonin (5-hydroxytryptamine [5-HT]) levels. 5-HT, a neurotransmitter involved in a number of physiological functions, is also known to enhance cognitive performance. The present study was designed to investigate the probable neurochemical mechanism responsible for the enhancement of memory following garlic administration. Sixteen adult locally bred male albino Wistar rats were divided into control (n = 8) and test (n = 8) groups. The test group was orally administered 250 mg/kg fresh garlic homogenate (FGH), while control animals received an equal amount of water daily for 21 days. Estimation of plasma free and total tryptophan (TRP) and whole brain TRP, 5-HT, and 5-hydroxyindole acetic acid (5-HIAA) was determined by high-performance liquid chromatography with electrochemical detection. For assessment of memory, a step-through passive avoidance paradigm (electric shock avoidance) was used. The results showed that the levels of plasma free TRP significantly increased (P < .01) and plasma total TRP significantly decreased (P < .01) in garlic-treated rats. Brain TRP, 5-HT, and 5-HIAA levels were also significantly increased following garlic administration. A significant improvement in memory function was exhibited by garlic-treated rats in the passive avoidance test. Increased brain 5-HT levels were associated with improved cognitive performance. The present results, therefore, demonstrate that the memory-enhancing effect of garlic may be associated with increased brain 5-HT metabolism in rats. The results further support the use of garlic as a food supplement for the enhancement of memory.

  1. Oral administration of insulin by means of liposomes in animal experiments

    International Nuclear Information System (INIS)

    Tragl, K.H.; Pohl, A.; Kinast, H.

    1979-01-01

    Liposomes are an effective vehicle for the oral administration of insulin. They are prepared from lipid emulsions by sonication and particles of homogeneous size are generated by elution through sepharose columns. Liposomes are taken up into the gastric mucosa by endocytosis and then transported to the liver via the portal circulation. Oral administration of 10 U insulin/kg body weight to rats is followed by a reduction in blood glucose to 67% of the initial value. When liposome-trapped insulin was injected intravenously a decrease in blood glucose to 40% of the initial value was obtained by the administration of 5 IU insulin/kg body weight. While the effect of orally-administered liposome-trapped insulin is obvious, the problems of standardization of the insulin content of the liposomes and the great variability of liposome uptake into the gastric mucosa by endocytosis remain unsolved. (author)

  2. Orally administered nicotine induces urothelial hyperplasia in rats and mice

    International Nuclear Information System (INIS)

    Dodmane, Puttappa R.; Arnold, Lora L.; Pennington, Karen L.; Cohen, Samuel M.

    2014-01-01

    Highlights: • Rats and mice orally administered with nicotine tartrate for total of 4 weeks. • No treatment-related death or whole body toxicity observed in any of the groups. • Urothelium showed simple hyperplasia in treated rats and mice. • No significant change in BrdU labeling index or SEM classification of urothelium. - Abstract: Tobacco smoking is a major risk factor for multiple human cancers including urinary bladder carcinoma. Tobacco smoke is a complex mixture containing chemicals that are known carcinogens in humans and/or animals. Aromatic amines a major class of DNA-reactive carcinogens in cigarette smoke, are not present at sufficiently high levels to fully explain the incidence of bladder cancer in cigarette smokers. Other agents in tobacco smoke could be excreted in urine and enhance the carcinogenic process by increasing urothelial cell proliferation. Nicotine is one such major component, as it has been shown to induce cell proliferation in multiple cell types in vitro. However, in vivo evidence specifically for the urothelium is lacking. We previously showed that cigarette smoke induces increased urothelial cell proliferation in mice. In the present study, urothelial proliferative and cytotoxic effects were examined after nicotine treatment in mice and rats. Nicotine hydrogen tartrate was administered in drinking water to rats (52 ppm nicotine) and mice (514 ppm nicotine) for 4 weeks and urothelial changes were evaluated. Histopathologically, 7/10 rats and 4/10 mice showed simple hyperplasia following nicotine treatment compared to none in the controls. Rats had an increased mean BrdU labeling index compared to controls, although it was not statistically significantly elevated in either species. Scanning electron microscopic visualization of the urothelium did not reveal significant cytotoxicity. These findings suggest that oral nicotine administration induced urothelial hyperplasia (increased cell proliferation), possibly due to a

  3. Development of a simple and sensitive liquid chromatography triple quadrupole mass spectrometry (LC-MS/MS) method for the determination of cannabidiol (CBD), Δ9-tetrahydrocannabinol (THC) and its metabolites in rat whole blood after oral administration of a single high dose of CBD.

    Science.gov (United States)

    Palazzoli, Federica; Citti, Cinzia; Licata, Manuela; Vilella, Antonietta; Manca, Letizia; Zoli, Michele; Vandelli, Maria Angela; Forni, Flavio; Cannazza, Giuseppe

    2018-02-20

    The investigation of the possible conversion of cannabidiol (CBD) into Δ 9 -tetrahydrocannabinol (THC) in vivo after oral administration of CBD is reported herein since recent publications suggested a rapid conversion in simulated gastric fluid. To this end, single high dose of CBD (50mg/kg) was administered orally to rats and their blood was collected after 3 and 6h. A highly sensitive and selective LC-MS/MS method was developed and fully validated in compliance with the Scientific Working Group of Forensic Toxicology (SWGTOX) standard practices for method validation in forensic toxicology. This method also involved the optimization of cannabinoids and their metabolites extraction in order to remove co-eluting phospholipids and increase the sensitivity of the MS detection. Neither THC nor its metabolites were detected in rat whole blood after 3 or 6h from CBD administration. After oral administration, the amount of CBD dissolved in olive oil was higher than that absorbed from an ethanolic solution. This could be explained by the protection of lipid excipients towards CBD from acidic gastric juice. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Novel oral administrated paclitaxel micelles with enhanced bioavailability and antitumor efficacy for resistant breast cancer.

    Science.gov (United States)

    Zhang, Ting; Luo, Jingwen; Fu, Yao; Li, Hanmei; Ding, Rui; Gong, Tao; Zhang, Zhirong

    2017-02-01

    Paclitaxel (PTX) is a widely used antineoplastic drug in clinic. Due to poor aqueous solubility, it is administrated by intravenous infusion of cremophor EL containing formulation with serious adverse effects. The low oral bioavailability is a great challenge for oral formulation development. In addition, P-gp mediated multidrug resistance limit its clinical use in various resistant cancers. In this study, a novel super-antiresistant PTX micelle formulation for oral administration was developed. A P-gp inhibitor, bromotetrandrine (W198) was co-encapsulated in the micelle. The micelles were composed of Solutol HS 15 and d-a-tocopheryl polyethylene glycol succinate to avoid Cremophor EL induced toxicity. The micelles were round with a mean particle size of ∼13nm and an encapsulation efficiency of ∼90%. A series of in vitro evaluations were performed in non-resistant MCF-7 cells and resistant MCF-7/Adr cells. The super-antiresistant PTX micelles showed higher cell uptake efficiency, significantly increased cytotoxicity and antimitotic effect in drug resistant MCF-7/Adr cells when compared with Taxol and other PTX micelle formulations. Compared with Taxol, the super-antiresistant PTX micelles significantly improved bioavailability after oral administration in rats, and inhibited tumor growth in multidrug resistance xenografted MCF-7/Adr nude mice. In summary, the noval super-antiresistant PTX micelles showed a great potential for oral delivery of PTX against resistant breast cancer. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Curcumin administration suppress acetylcholinesterase gene expression in cadmium treated rats.

    Science.gov (United States)

    Akinyemi, Ayodele Jacob; Oboh, Ganiyu; Fadaka, Adewale Oluwaseun; Olatunji, Babawale Peter; Akomolafe, Seun

    2017-09-01

    Curcumin, the main polyphenolic component of turmeric (Curcuma longa) rhizomes have been reported to exert anticholinesterase potential with limited information on how they regulate acetylcholinesterase (AChE) gene expression. Hence, this study sought to evaluate the effect of curcumin on cerebral cortex acetylcholinesterase (AChE) activity and their mRNA gene expression level in cadmium (Cd)-treated rats. Furthermore, in vitro effect of different concentrations of curcumin (1-5μg/mL) on rat cerebral cortex AChE activity was assessed. Animals were divided into six groups (n=6): group 1 serve as control (without Cd) and receive saline/vehicle, group 2 receive saline plus curcumin at 25mg/kg, group 3 receive saline plus curcumin 50mg/kg, group 4 receive Cd plus vehicle, group 5 receive Cd plus curcumin at 25mg/kg and group 6 receive Cd plus curcumin at 50mg/kg. Rats received Cd (2.5mg/kg) and curcumin (25 and 50mg/kg, respectively) by oral gavage for 7days. Acetylcholinesterase activity was measured by Ellman's method and AChE expression was carried out by a quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) assay. We observed that acute administration of Cd increased acetylcholinesterase activity and in addition caused a significant (Pcurcumin inhibited AChE activity and alters AChE mRNA levels when compared to Cd-treated group. In addition, curcumin inhibits rat cerebral cortex AChE activity in vitro. In conclusion, curcumin exhibit anti-acetylcholinesterase activity and suppressed AChE mRNA gene expression level in Cd exposed rats, thus providing some biochemical and molecular evidence on the therapeutic effect of this turmeric-derived compound in treating neurological disorders including Alzheimer's disease. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Effect of DA-8031, a novel oral compound for premature ejaculation, on male rat sexual behavior.

    Science.gov (United States)

    Kang, Kyung Koo; Sung, Ji Hyun; Kim, Soon Hoe; Lee, Sukhyang

    2014-03-01

    DA-8031 is a potent and selective serotonin transporter inhibitor developed for the treatment of premature ejaculation. The aim of the present study was to investigate the effects of DA-8031 on male sexual behavior in a rat model. Sexual behavior was examined after an acute oral administration of 10, 30 or 100 mg/kg of DA-8031 in copulation studies with female rats. Pharmacokinetic parameters were calculated after oral administration of DA-8031 at a dose level of 30 mg/kg. DA-8031 treatment produced a dose-dependent increase in ejaculation latency time and showed statistical significance at 30 and 100 mg/kg dosage levels compared with the vehicle (P DA-8031 treatment reduced the mean number of ejaculations in a dose-dependent manner. No changes in post-ejaculatory interval, numbers of mounts, intromissions or ejaculations were observed at any dose. In pharmacokinetic study, the blood concentration of DA-8031 peaked at 0.38 ± 0.14 h after oral administration, and then rapidly declined with a half-life of 1.79 ± 0.32 h. Treatment with DA-8031 delays the ejaculation latency time without affecting the initiation of mounting behavior or post-ejaculatory interval in rats. Furthermore, DA-8031 is rapidly absorbed and eliminated after oral administration in rats. These preclinical findings provide a clue for the clinical testing of DA-8031 as an "on-demand" agent for premature ejaculation. © 2013 The Japanese Urological Association.

  7. Anti-tumour immune effect of oral administration of Lactobacillus

    Indian Academy of Sciences (India)

    Our results indicated that oral administration with L. plantarum inhibited CT26 cell ... (but not IL-4 or IL-17) production, and promotion of Th1-type CD4+ T differentiation. ... College of Animal Science and Technology, Jilin Agricultural University, ...

  8. Oral administration of fisetin promotes the induction of hippocampal long-term potentiation in vivo

    OpenAIRE

    Wen-bin He; Kazuho Abe; Tatsuhiro Akaishi

    2018-01-01

    To explore memory enhancing effect of the flavonoid fisetin, we investigated the effect of oral administration of flavonoids on the induction of long-term potentiation (LTP) at hippocampal CA1 synapses of anesthetized rats. Among four flavonoids (fisetin, quercetin, luteolin and myricetin) tested, only fisetin significantly facilitated the induction of hippocampal LTP. The effect of oral fisetin was abolished by intracerebroventricular injection of U0126, an agent that was previously found to...

  9. Effect of titanium dioxide nanoparticles on the cardiovascular system after oral administration.

    Science.gov (United States)

    Chen, Zhangjian; Wang, Yun; Zhuo, Lin; Chen, Shi; Zhao, Lin; Luan, Xianguo; Wang, Haifang; Jia, Guang

    2015-12-03

    Titanium dioxide nanoparticles (TiO2 NPs) have been widely used in various consumer products, especially food and personal care products. Compared to the well-characterized adverse cardiovascular effect of inhaled ambient ultrafine particles, research on the health response to orally administrated TiO2 NPs is still limited. In our study, we performed an in vivo study in Sprague-Dawley rats to understand the cardiovascular effect of TiO2 NPs after oral intake. After daily gastrointestinal administration of TiO2 NPs at 0, 2, 10, 50 mg/kg for 30 and 90 days, heart rate (HR), blood pressure, blood biochemical parameters and histopathology of cardiac tissues was assessed to quantify cardiovascular damage. Mild and temporary reduction of HR and systolic blood pressure as well as an increase of diastolic blood pressure was observed after daily oral administration of TiO2 NPs for 30 days. Injury of cardiac function was observed after daily oral administration of TiO2 NPs for 90 days as reflected in decreased activities of lactate dehydrogenase (LDH), alpha-hydroxybutyrate dehydrogenase (HBDH) and creatine kinase (CK). Increased white blood cells count (WBC) and granulocytes (GRN) in blood as well as increased concentrations of tumor necrosis factor α (TNF α) and interleukin 6 (IL-6) in the serum indicated inflammatory response initiated by TiO2 NPs exposure. It was hypothesize that cardiac damage and inflammatory response are the possible mechanisms of the adverse cardiovascular effects induced by orally administrated TiO2 NPs. Data from our study suggested that even at low dose of TiO2 NPs can induce adverse cardiovascular effects after 30 days or 90 days of oral exposure, thus warranting concern for the dietary intake of TiO2 NPs for consumers. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  10. Effects of a prolonged administration of valepotriates in rats on the mothers and their offspring.

    Science.gov (United States)

    Tufik, S; Fujita, K; Seabra, M de L; Lobo, L L

    1994-01-01

    Valeriana officinalis L. (Valerianaceae) is widely known to be associated with sedative properties. The effects of a valepotriates mixtures on mothers and progeny were evaluated in rats. A 30-day administration of valepotriates did not change the average length of estral cycle, nor the number of estrous phases during this period. Also, there were no changes on the fertility index. Fetotoxicity and external examination studies did not show differences, although internal examination revealed an increase in number of retarded ossification after the highest doses employed--12 and 24 mg/kg. No changes were detected in the development of the offspring after treatment during pregnancy. As for temperature, valepotriates caused a hypothermizant effect after administration by the intraperitoneal route but not after oral administration. Generally, the valepotriates employed induced some alterations after administration by the intraperitoneal route, but doses given orally were innocuous to pregnant rats and their offspring.

  11. Effects of long-term light, darkness and oral administration of melatonin on serum levels of melatonin

    OpenAIRE

    Naser Farhadi; Majid Gharghani; Zahra Farhadi

    2016-01-01

    Background: Continuous light or darkness has various effects on different systems. In the present research work, the effects of constant light and darkness exposure of male rats and oral administration of exogenous melatonin on the serum levels of melatonin have been studied. Methods: Thirty adult male Wistar rats were divided into six groups of: (1) Control, (2) melatonin, (3) light, (4) light and melatonin, (5) darkness, and (6) darkness and melatonin. All groups were placed according to...

  12. Labeling of red blood cells with Tc-99m after oral administration of SnCl2. Concise communication

    International Nuclear Information System (INIS)

    Patel, M.C.; Parab, P.B.; Samuel, A.M.; Ganatra, R.D.

    1979-01-01

    In vivo labeling of red blood cells with Tc-99m was possible after prior oral administration of SnCl 2 , both in rats and human volunteers. Absorption of oral SnCl 2 was low but sufficient for more than 95% labeling efficiency. Prior i.v. administration of stannous chloride is known to induce in vivo labeling of red blood cells with pertechnetate. We have observed that such labeling is possible even after oral administration of stannous chloide. Nearly 95% of the circulating radioactivity and 93.7% of the administered radioactivity was in RBCs 30 min after i.v. injection of /sup 99m/TcO 4 - in rats that were fed 5 mg of stannous chloride (3.13 mg Sn 2+ ion) 2 hr before injection. Red blood cells from four human volunteers could bind pertechnetate, both in vitro and in vivo, after oral administration of 100 mg of SnCl 2 . We have obtained a blood-pool image of the human heart by labeling the RBCs in vivo by this method. We have also studied various parameters affecting the in vivo binding of RBCs with Tc-99m - such as the amount of orally administered SnCl 2 , the time of injection of radionuclide after oral SnCl 2 , and the optimum time for the imaging

  13. Distribution of silver in rats following 28 days of repeated oral exposure to silver nanoparticles or silver acetate

    DEFF Research Database (Denmark)

    Löschner, Katrin; Hadrup, Niels; Qvortrup, Klaus

    2011-01-01

    Background: The study investigated the distribution of silver after 28 days repeated oral administration of silver nanoparticles (AgNPs) and silver acetate (AgAc) to rats. Oral administration is a relevant route of exposure because of the use of silver nanoparticles in products related to food...... and food contact materials. Results: AgNPs were synthesized with a size distribution of 14 ± 4 nm in diameter (90% of the nanoparticle volume) and stabilized in aqueous suspension by the polymer polyvinylpyrrolidone (PVP). The AgNPs remained stable throughout the duration of the 28-day oral toxicity study...... in rats. The organ distribution pattern of silver following administration of AgNPs and AgAc was similar. However the absolute silver concentrations in tissues were lower following oral exposure to AgNPs. This was in agreement with an indication of a higher fecal excretion following administration of Ag...

  14. Fenproporex and amphetamine pharmacokinetics in oral fluid after controlled oral administration of fenproporex.

    Science.gov (United States)

    Comiran, Eloisa; Souza, Daniele Zago; Boehl, Paula Otero; Cássia Mariotti, Kristiane de; Pechansky, Flavio; Duarte, Paulina do Carmo Arruda Vieira; De Boni, Raquel Brandini; Fröehlich, Pedro Eduardo; Limberger, Renata Pereira

    2012-10-01

    Fenproporex hydrochloride (FEN) is an anorectic drug used in the treatment of obesity, and its major metabolite is amphetamine (AMP), another central nervous system stimulant. The concentration versus time profile of FEN and its metabolite AMP has been described in classic biological matrices such as plasma and urine; however, there are no reports of such data in oral fluid. The aim of this study is to describe the pharmacokinetics of FEN and AMP in oral fluid after intake of FEN. Twenty-five milligrams of FEN (1 capsule of Desobesi-m) was orally administered to 6 male volunteers, and oral fluid samples were collected with a Quantisal device during 24.00 hours after drug ingestion. These samples were submitted to solid-phase microextraction before analysis by gas chromatography-mass spectrometry in the selected-ion-monitoring mode, using deuterium-labeled AMP as internal standard. After FEN administration, both analytes could be detected in oral fluid of all volunteers with an initial detection time varying from 0.50 to 1.00 hour. FEN peak concentrations occurred between 1.00 and 1.50 hours after administration and were between 70.7 and 227.5 μg/L. For AMP, peak concentration occurred between 1.50 and 4.00 hours, reaching 33.0-150.9 μg/L. The authors observed that oral administration of FEN resulted in significant amounts of FEN and AMP in oral fluid, showing that oral fluid could be a biological matrix suitable for pharmacokinetic studies for both analytes. Using a compartmental approach, FEN data were best fitted by 1-compartment model with first-order input and output, whereas AMP followed a 2-compartment model with first-order input and output.

  15. Oral administration of fisetin promotes the induction of hippocampal long-term potentiation in vivo

    Directory of Open Access Journals (Sweden)

    Wen-bin He

    2018-01-01

    Full Text Available To explore memory enhancing effect of the flavonoid fisetin, we investigated the effect of oral administration of flavonoids on the induction of long-term potentiation (LTP at hippocampal CA1 synapses of anesthetized rats. Among four flavonoids (fisetin, quercetin, luteolin and myricetin tested, only fisetin significantly facilitated the induction of hippocampal LTP. The effect of oral fisetin was abolished by intracerebroventricular injection of U0126, an agent that was previously found to inhibit its effect in hippocampal slices in vitro. These results suggest that orally administered fisetin crosses the blood–brain barrier and promotes synaptic functions in the hippocampus.

  16. Unraveling the Rat Intestine, Spleen and Liver Genome-Wide Transcriptome after the Oral Administration of Lavender Oil by a Two-Color Dye-Swap DNA Microarray Approach.

    Science.gov (United States)

    Kubo, Hiroko; Shibato, Junko; Saito, Tomomi; Ogawa, Tetsuo; Rakwal, Randeep; Shioda, Seiji

    2015-01-01

    The use of lavender oil (LO)--a commonly, used oil in aromatherapy, with well-defined volatile components linalool and linalyl acetate--in non-traditional medicine is increasing globally. To understand and demonstrate the potential positive effects of LO on the body, we have established an animal model in this current study, investigating the orally administered LO effects genome wide in the rat small intestine, spleen, and liver. The rats were administered LO at 5 mg/kg (usual therapeutic dose in humans) followed by the screening of differentially expressed genes in the tissues, using a 4×44-K whole-genome rat chip (Agilent microarray platform; Agilent Technologies, Palo Alto, CA, USA) in conjunction with a dye-swap approach, a novelty of this study. Fourteen days after LO treatment and compared with a control group (sham), a total of 156 and 154 up (≧ 1.5-fold)- and down (≦ 0.75-fold)-regulated genes, 174 and 66 up- (≧ 1.5-fold)- and down (≦ 0.75-fold)-regulated genes, and 222 and 322 up- (≧ 1.5-fold)- and down (≦ 0.75-fold)-regulated genes showed differential expression at the mRNA level in the small intestine, spleen and liver, respectively. The reverse transcription-polymerase chain reaction (RT-PCR) validation of highly up- and down-regulated genes confirmed the regulation of the Papd4, Lrp1b, Alb, Cyr61, Cyp2c, and Cxcl1 genes by LO as examples in these tissues. Using bioinformatics, including Ingenuity Pathway Analysis (IPA), differentially expressed genes were functionally categorized by their Gene Ontology (GO) and biological function and network analysis, revealing their diverse functions and potential roles in LO-mediated effects in rat. Further IPA analysis in particular unraveled the presence of novel genes, such as Papd4, Or8k5, Gprc5b, Taar5, Trpc6, Pld2 and Onecut3 (up-regulated top molecules) and Tnf, Slc45a4, Slc25a23 and Samt4 (down-regulated top molecules), to be influenced by LO treatment in the small intestine, spleen and liver

  17. Unraveling the Rat Intestine, Spleen and Liver Genome-Wide Transcriptome after the Oral Administration of Lavender Oil by a Two-Color Dye-Swap DNA Microarray Approach.

    Directory of Open Access Journals (Sweden)

    Hiroko Kubo

    Full Text Available The use of lavender oil (LO--a commonly, used oil in aromatherapy, with well-defined volatile components linalool and linalyl acetate--in non-traditional medicine is increasing globally. To understand and demonstrate the potential positive effects of LO on the body, we have established an animal model in this current study, investigating the orally administered LO effects genome wide in the rat small intestine, spleen, and liver. The rats were administered LO at 5 mg/kg (usual therapeutic dose in humans followed by the screening of differentially expressed genes in the tissues, using a 4×44-K whole-genome rat chip (Agilent microarray platform; Agilent Technologies, Palo Alto, CA, USA in conjunction with a dye-swap approach, a novelty of this study. Fourteen days after LO treatment and compared with a control group (sham, a total of 156 and 154 up (≧ 1.5-fold- and down (≦ 0.75-fold-regulated genes, 174 and 66 up- (≧ 1.5-fold- and down (≦ 0.75-fold-regulated genes, and 222 and 322 up- (≧ 1.5-fold- and down (≦ 0.75-fold-regulated genes showed differential expression at the mRNA level in the small intestine, spleen and liver, respectively. The reverse transcription-polymerase chain reaction (RT-PCR validation of highly up- and down-regulated genes confirmed the regulation of the Papd4, Lrp1b, Alb, Cyr61, Cyp2c, and Cxcl1 genes by LO as examples in these tissues. Using bioinformatics, including Ingenuity Pathway Analysis (IPA, differentially expressed genes were functionally categorized by their Gene Ontology (GO and biological function and network analysis, revealing their diverse functions and potential roles in LO-mediated effects in rat. Further IPA analysis in particular unraveled the presence of novel genes, such as Papd4, Or8k5, Gprc5b, Taar5, Trpc6, Pld2 and Onecut3 (up-regulated top molecules and Tnf, Slc45a4, Slc25a23 and Samt4 (down-regulated top molecules, to be influenced by LO treatment in the small intestine, spleen and

  18. Effect of a thiolated polymer on oral paclitaxel absorption and tumor growth in rats.

    Science.gov (United States)

    Föger, Florian; Malaivijitnond, Suchinda; Wannaprasert, Thanakul; Huck, Christian; Bernkop-Schnürch, Andreas; Werle, Martin

    2008-02-01

    The anticancer agent paclitaxel is currently commercially available only as an infusion due to its low oral bioavailability. An oral formulation would be highly beneficial for patients. Besides the low solubility, the main reason for the limited oral bioavailability of paclitaxel is that it is a substrate of the efflux pump P-glycoprotein (P-gp). Recently, it has been demonstrated that P-gp can be inhibited by thiolated polymers. In this study, an oral paclitaxel formulation based on thiolated polycarbophil was evaluated in vivo in wild-type rats and in mammary cancer-induced rats. The paclitaxel plasma level after a single administration of paclitaxel was observed for 12 h in healthy rats. Moreover, cancer-induced rats were treated weekly for 5 weeks with the novel formulation. It was demonstrated that (1) co-administration of thiolated polycarbophil significantly improved paclitaxel plasma levels, (2) a more constant pharmacokinetic profile could be achieved and (3) the tumor growth was reduced. These effects can most likely be attributed to P-gp inhibition. According to the achieved results, thiolated polymers are believed to be interesting tools for the delivery of P-gp substrates such as paclitaxel.

  19. The engagement of oral-associated lymphoid tissues during oral versus gastric antigen administration.

    Science.gov (United States)

    Bankvall, Maria; Östberg, Anna-Karin; Jontell, Mats; Wold, Agnes; Östman, Sofia

    2016-09-01

    The role of oral-associated lymphoid tissues during induction of oral tolerance still remains elusive. Therefore, the aim was to compare T-cell activation and induction of tolerance to ovalbumin (OVA) presented through either of two routes; deposited into the oral cavity, or the stomach, thereby bypassing the oral cavity. OVA was administered by the oral or gastric route to BALB/c mice that had received OVA-specific DO11.10+ CD4(+) T cells, stained with CellTrace(™) Violet dye, through intravenous injection. Proliferating OVA-specific T cells were detected in the nose-associated lymphoid tissues (NALT) and the cervical, mesenteric and peripheral lymph nodes at different time-points following OVA exposure. OVA-specific T-cell proliferation was initially observed in the NALT 1 hr after oral, but not gastric, administration. However, at day 1, proliferation at this site was also detected after gastric administration and profound proliferation was observed at all sites by day 4. For the oral route the degree of proliferation observed was lower in the peripheral lymph nodes by day 4 compared with the other sites. These results demonstrate a similar activation pattern achieved by the two routes. However, the NALT distinguishes itself as a site of rapid T-cell activation towards fed antigens irrespective of feeding regimen. To evaluate induction of tolerance a semi-effective OVA dose was used, to detect differences in the degree of tolerance achieved. This was performed in a model of OVA-induced airway hypersensitivity. No differences in tolerance induction were observed between the two administration routes. © 2016 John Wiley & Sons Ltd.

  20. Pharmacokinetic evaluation of the interaction between oral kaempferol and ethanol in rats.

    Science.gov (United States)

    Zhou, Zhaoxiang; Wang, Meng; Guo, Zengjun; Zhang, Xiaoying

    2016-12-01

    This study was aimed at investigating the effect of ethanol on oral bioavailability of kaempferol in rats, namely, at disclosing their possible interaction. Kaempferol (100 or 250 mg kg-1 bm) was administered to the rats by oral gavage with or without ethanol (600 mg kg-1 bm) co-administration. Intravenous administration (10 and 25 mg kg-1 bm) of kaempferol was used to determine the bioavailability. The concentration of kaempferol in plasma was estimated by ultra high performance liquid chromatography. During coadministration, a significant increase of the area under the plasma concentration-time curve as well as the peak concentration were observed, along with a dramatic decrease in total body clearance. Consequently, the bioavailability of kaempferol in oral control groups was 3.1 % (100 mg kg-1 bm) and 2.1 % (250 mg kg-1 bm). The first was increased by 4.3 % and the other by 2.8 % during ethanol co-administration. Increased permeability of cell membrane and ethanolkaempferol interactions on CYP450 enzymes may enhance the oral bioavailability of kaempferol in rats.

  1. Supraspinally-administered agmatine attenuates the development of oral fentanyl self-administration

    Science.gov (United States)

    Wade, Carrie L.; Schuster, Daniel J.; Domingo, Kristine M.; Kitto, Kelley F.; Fairbanks, Carolyn A.

    2009-01-01

    The decarboxylation product of arginine, agmatine, has effectively reduced or prevented opioid-induced tolerance and dependence when given either systemically (intraperitoneally or subcutaneously) or centrally (intrathecally or intracerebroventricularly). Systemically administered agmatine also reduces the escalation phase of intravenous fentanyl self-administration in rats. The present study assessed whether centrally (intracerebroventricular, i.c.v.) delivered agmatine could prevent the development of fentanyl self-administration in mice. Mice were trained to respond under a fixed-ratio 1 (FR1) schedule for either fentanyl (0.7 μg/70 μl, p.o.) or food reinforcement. Agmatine (10 nmol/5 μl), injected i.c.v. 12-14h before the first session and every other evening (12-14h before session) for 2 weeks, completely attenuated oral fentanyl self-administration (but not food-maintained responding) compared to saline-injected controls. When agmatine was administered after fentanyl self-administration had been established (day 8) it had no attenuating effects on bar pressing. This dose of agmatine does not decrease locomotor activity as assessed by rotarod. The present findings significantly extend the previous observation that agmatine prevents opioid-maintained behavior to a chronic model of oral fentanyl self-administration as well as identifying a supraspinal site of action for agmatine inhibition of drug addiction. PMID:18495108

  2. A preliminary 13-week oral toxicity study of ginger oil in male and female Wistar rats.

    Science.gov (United States)

    Jeena, Kottarapat; Liju, Vijayastelter B; Kuttan, Ramadasan

    2011-12-01

    Zingiber officinale Roscoe, ginger, is a major spice extensively used in traditional medicine. The toxicity profile of ginger oil was studied by subchronic oral administration for 13 weeks at doses of 100, 250, and 500 mg/kg per day to 6 groups of Wistar rats (5/sex per dose). Separate groups of rats (5/sex per group) received either paraffin oil (vehicle) or were untreated and served as comparative control groups. There was no mortality and no decrease in body weight or food consumption as well as selective organ weights during the study period. Administration of ginger oil to rats did not produce any treatment-related changes in hematological parameters, hepatic, renal functions, serum electrolytes, or in histopathology of selected organs. The major component of ginger oil was found to be zingiberene (31.08%), and initial studies indicated the presence of zingiberene in the serum after oral dosing. These results confirmed that ginger oil is not toxic to male and female rats following subchronic oral administrations of up to 500 mg/kg per day (no observed adverse effect level [NOAEL]).

  3. Reducing radiation exposure during oral I-131 therapy administration

    International Nuclear Information System (INIS)

    Trujillo, J.; Krinsky, S.; Wilson, B.; Teague, E.

    1982-01-01

    A new, closed-system method to reduce air-, direct-, and incidental-contamination during therapeutic administration of oral I-131 was experimentally evaluated on twelve patients. We studied a standard control population using the routine practice of drinking the solution through a straw and compared results with our new technique. Various measurements were performed throughout all phases of dose administration to assess the relative difference of the two approaches. Using the closed system method before and during iodine administration revealed between 100 and 1000 times less activity per millimeter of air sample; whereas, the direct radiation exposure values were higher for the control population. Both the experimental and control methods had similar levels of incidental contamination

  4. Effectiveness of intragastric administration of 8102 for removal of thorium-234 in rats

    International Nuclear Information System (INIS)

    Luo Meichu; Li Landi; Sun Meizhen; Ye Qian; Liu Yi

    1992-01-01

    8102, a 1,2-dihydroxy-3,6-bismethylamino diacetic derivative, is a new chelating agent for decorporation of radionuclides. The effectiveness of intragastric administration of this drug at different doses (50-1000 mg/kg of body) and at different times before or after giving thorium-234 in rats was reported. The results show that for rats given intragastricly 1000 mg/kg of 8102, the excretion of thorium-234 in urine for first two days is 4.5 times more than that for control rats and accumulations of thorium-234 in liver, skeleton and kidney for these rats were 30%, 62% and 68% as those for control rats, respectively. The effectiveness was reduced with decrease in dosage of 8102. Administration of 8102 at 1 or 2 h before injection of thorium-234 can improve the effectiveness for decorporation of thorium-234: accumulation of thorium-234 in liver was markedly less than that for rats given 8102 immediately after injection of thorium-234. Delayed administration of 9102 resulted in reduction of the effectiveness. The practicality of oral administration of 8102 in clinic for decorporation of radionuclides was discussed

  5. Enhancement of brain serotonin by long term oral administration of tryptophan produces no effect on food intake

    International Nuclear Information System (INIS)

    Haider, S.; Akhtar, N.; Kidwai, I.M.; Haleem, D.J.

    1999-01-01

    L-tryptophan (TRP) is widely used to enhance serotonin mediate brain functions. In the Present study effects of oral administration of TRP (100mg/kg) daily for 5 weeks, were investigated on the food intake, growth rate and brain indole amine metabolism in young rats. TRP ingestion significantly increased growth rate but did not alter food intake in rats. The levels of TRP and 5-hydroxytryptamine (5-HT) were higher in the hypothalamus of TRP treated rats. Increases of 5-hydroxyindole acetic acid (5-HIAA) were hot significant. TRP, 5-HT and 5-HIAA all increased in the rest of the brain of TRP treated rats. The present study shows that long term TRP administration thorough increases brain 5-ht metabolism and turnover but functional responses to 5-ht are not necessarily increases. (author)

  6. Alleviation of metabolic abnormalities induced by excessive fructose administration in Wistar rats by Spirulina maxima.

    Science.gov (United States)

    Jarouliya, Urmila; Zacharia, J Anish; Kumar, Pravin; Bisen, P S; Prasad, G B K S

    2012-03-01

    Diabetes mellitus is a metabolic disorder characterized by hyperglycaemia. Several natural products have been isolated and identified to restore the complications of diabetes. Spirulina maxima is naturally occurring fresh water cyanobacterium, enriched with proteins and essential nutrients. The aim of the study was to determine whether S. maxima could serve as a therapeutic agent to correct metabolic abnormalities induced by excessive fructose administration in Wistar rats. Oral administration of 10 per cent fructose solution to Wistar rats (n = 5 in each group) for 30 days resulted in hyperglycaemia and hyperlipidaemia. Aqueous suspension of S. maxima (5 or 10%) was also administered orally once daily for 30 days. The therapeutic potential of the preparation with reference to metformin (500 mg/kg) was assessed by monitoring various biochemical parameters at 10 day intervals during the course of therapy and at the end of 30 days S. maxima administration. Significant (Pmaxima aquous extract. Co-administration of S. maxima extract (5 or 10% aqueous) with 10 per cent fructose solution offered a significant protection against fructose induced metabolic abnormalities in Wistar rats. The present findings showed that S. maxima exhibited anti-hyperglycaemic, anti-hyperlipidaemic and hepatoprotective activity in rats fed with fructose. Further studies are needed to understand the mechanisms.

  7. Fluoxetine Dose and Administration Method Differentially Affect Hippocampal Plasticity in Adult Female Rats

    Science.gov (United States)

    Pawluski, Jodi L.; van Donkelaar, Eva; Abrams, Zipporah; Steinbusch, Harry W. M.; Charlier, Thierry D.

    2014-01-01

    Selective serotonin reuptake inhibitor medications are one of the most common treatments for mood disorders. In humans, these medications are taken orally, usually once per day. Unfortunately, administration of antidepressant medications in rodent models is often through injection, oral gavage, or minipump implant, all relatively stressful procedures. The aim of the present study was to investigate how administration of the commonly used SSRI, fluoxetine, via a wafer cookie, compares to fluoxetine administration using an osmotic minipump, with regards to serum drug levels and hippocampal plasticity. For this experiment, adult female Sprague-Dawley rats were divided over the two administration methods: (1) cookie and (2) osmotic minipump and three fluoxetine treatment doses: 0, 5, or 10 mg/kg/day. Results show that a fluoxetine dose of 5 mg/kg/day, but not 10 mg/kg/day, results in comparable serum levels of fluoxetine and its active metabolite norfluoxetine between the two administration methods. Furthermore, minipump administration of fluoxetine resulted in higher levels of cell proliferation in the granule cell layer (GCL) at a 5 mg dose compared to a 10 mg dose. Synaptophysin expression in the GCL, but not CA3, was significantly lower after fluoxetine treatment, regardless of administration method. These data suggest that the administration method and dose of fluoxetine can differentially affect hippocampal plasticity in the adult female rat. PMID:24757568

  8. Fluoxetine Dose and Administration Method Differentially Affect Hippocampal Plasticity in Adult Female Rats

    Directory of Open Access Journals (Sweden)

    Jodi L. Pawluski

    2014-01-01

    Full Text Available Selective serotonin reuptake inhibitor medications are one of the most common treatments for mood disorders. In humans, these medications are taken orally, usually once per day. Unfortunately, administration of antidepressant medications in rodent models is often through injection, oral gavage, or minipump implant, all relatively stressful procedures. The aim of the present study was to investigate how administration of the commonly used SSRI, fluoxetine, via a wafer cookie, compares to fluoxetine administration using an osmotic minipump, with regards to serum drug levels and hippocampal plasticity. For this experiment, adult female Sprague-Dawley rats were divided over the two administration methods: (1 cookie and (2 osmotic minipump and three fluoxetine treatment doses: 0, 5, or 10 mg/kg/day. Results show that a fluoxetine dose of 5 mg/kg/day, but not 10 mg/kg/day, results in comparable serum levels of fluoxetine and its active metabolite norfluoxetine between the two administration methods. Furthermore, minipump administration of fluoxetine resulted in higher levels of cell proliferation in the granule cell layer (GCL at a 5 mg dose compared to a 10 mg dose. Synaptophysin expression in the GCL, but not CA3, was significantly lower after fluoxetine treatment, regardless of administration method. These data suggest that the administration method and dose of fluoxetine can differentially affect hippocampal plasticity in the adult female rat.

  9. Safety of 8-weeks oral administration of Arctium lappa L.

    Science.gov (United States)

    Bok, So-Hyeon; Cho, Seung Sik; Bae, Chun-Sik; Park, Dae-Hun; Park, Kyung-Mok

    2017-09-01

    Recently, worldwide dietary reference intakes have been considered an important guideline for public health. Some governments and the World Health Organization (WHO) provide guidelines concerning dietary intake. Although an ingredient may have a history of use as a culinary material, changes in the environment over time suggest that the acceptable maximum intake each of food/culinary material should be regularly evaluated. Arctium lappa L. has been used as a culinary material for many centuries in Korea and Japan and some recent studies have reported related therapeutic effects. However, there are no reports on the safety of repeated oral administration. In this study, we evaluated the safety of a 8-weeks repeated oral intake of A. lappa . We concluded that treatment with lappa , which was within the safety range, resulted in body weight decrease and blood glucose suppression.

  10. Biological effects of fractionated administration of radioactive phosphorus in rats

    International Nuclear Information System (INIS)

    Takizawa, Shoichi; Ohtsuka, Shoichiro; Morii, Kazuyo; Hirose, Fumio

    1978-01-01

    Female rats were given 1 μCi per g body weight of 32 P intraperitoneally four or eight times at intervals of two weeks, and half the rats received ovariectomy after two weeks. Various damages in the rats which received ovariectomy were compared with those in rats which did not receive ovariectomy. As to a change of body weight, an increase of body weight observed through the whole observation term after desexualization (for 11 months after the administration) was inhibited, and there was not any difference between ovariectomized and not-ovariectomized rats. The number of leukocytes decreased just after the administration. It took one month and a half in 4 times administration and three months and a half in 8 times administration to recover the number of leukocytes to normal values. There was no effect of desexualization. On the group administered 32 P 8 times the number of erythrocytes tended to decrease markely, but it recovered to a normal condition rapidly after the finish of the administration. As to onset of tumors, osteosarcoma occurred with high incidence (63%) regardless of presence of desexualization and frequency of the administration. The incidence of leukemia was about 15%. One case of breast tumor was recognized in nonovariectomized rats. Malignant tumors were not recognized in cases with normal sexual cycle for 8 to 10 months after the beginning of the administration. (Kanao, N.)

  11. Effect of Acute Administration of loganin on Spatial Memory in Diabetic Male Rats

    Directory of Open Access Journals (Sweden)

    Gisou Mohaddes

    2013-02-01

    Full Text Available Purpose: Diabetes is associated with memory and learning disorder. The purpose of this study is to determine the effect of acute oral administration of loganin on memory in diabetic male rats. Methods: 42 male Wistar rats (250-300 g were divided into six groups: Control, Diabetic (1 week, Diabetic (12 weeks, Loganin, Diabetic (1 week + Loganin, Diabetic (12 weeks + Loganin. Diabetes was induced by IP injection of Streptozotocin (60 mg/kg. Loganin (40 mg/kg, po was administrated 1 hour before test. Then, spatial memory was compared between groups with Morris Water Maze tests. Results: Administration of loganin during acquisition, significantly (p<0.05 decreased both escape latency and traveled distance to find hidden platform in 1 and 12 weeks diabetic rats. In evaluation of recall phase of memory, loganin significantly (p<0.05 increased time and distance spent in the target quadrant in 1 and 12 weeks diabetic rats. Conclusion: Acute administration of loganin could improve spatial memory in diabetic rats.

  12. Oral exposure to low-dose of nonylphenol impairs memory performance in Sprague-Dawley rats.

    Science.gov (United States)

    Kawaguchi, Shinichiro; Kuwahara, Rika; Kohara, Yumi; Uchida, Yutaro; Oku, Yushi; Yamashita, Kimihiro

    2015-02-01

    Nonylphenol ethoxylate (NPE) is a non-ionic surfactant, that is degraded to short-chain NPE and 4-nonylphenol (NP) by bacteria in the environment. NP, one of the most common environmental endocrine disruptors, exhibits weak estrogen-like activity. In this study, we investigated whether oral administration of NP (at 0.5 and 5 mg/kg doses) affects spatial learning and memory, general activity, emotionality, and fear-motivated learning and memory in male and female Sprague-Dawley (SD) rats. SD rats of both sexes were evaluated using a battery of behavioral tests, including an appetite-motivated maze test (MAZE test) that was used to assess spatial learning and memory. In the MAZE test, the time required to reach the reward in male rats treated with 0.5 mg/kg NP group and female rats administered 5 mg/kg NP was significantly longer than that for control animals of the corresponding sex. In other behavioral tests, no significant differences were observed between the control group and either of the NP-treated groups of male rats. In female rats, inner and ambulation values for animals administered 0.5 mg/kg NP were significantly higher than those measured in control animals in open-field test, while the latency in the group treated with 5 mg/kg NP was significantly shorter compared to the control group in step-through passive avoidance test. This study indicates that oral administration of a low-dose of NP slightly impairs spatial learning and memory performance in male and female rats, and alters emotionality and fear-motivated learning and memory in female rats only.

  13. Ninety-day oral toxicity study of rice-derived γ-oryzanol in Sprague-Dawley rats.

    Science.gov (United States)

    Moon, Seol-Hee; Kim, Duyeol; Shimizu, Norihito; Okada, Tadashi; Hitoe, Shoketsu; Shimoda, Hiroshi

    2017-01-01

    A 90-day oral toxicity study of γ-oryzanol, a rice-derived triterpenoid ferulate, was performed by oral gavage administration to male and female Sprague-Dawley rats at doses of 0, 1000, and 2000 mg/kg body weight/day. All rats administered γ-oryzanol survived throughout the study period. Both male and female rats showed no toxicologically significant changes of the general signs, examination findings, body weight, food consumption, functional observational battery results, ophthalmological findings, urinalysis, hematology tests, clinical chemistry tests, organ weights, and necropsy findings. Moreover, there were no histopathological changes related to administration of γ-oryzanol in males and females from the 2000 mg/kg body weight/day group. In conclusion, the no observed adverse effect level (NOAEL) of γ-oryzanol exceeded 2000 mg/kg body weight/day for both male and female rats under the conditions of this study.

  14. Four-week oral toxicity study with erythritol in rats

    NARCIS (Netherlands)

    Til, H.P.; Modderman, J.

    1996-01-01

    Erythritol was orally administered to Wistar rats at dietary levels of 0, 5, and 10% for 4 weeks. Soft stools and diarrhea were observed in male and female animals of the 10% group and in female animals of the 5% group. These symptoms disappeared during the course of the study. Mean body weights of

  15. Two cases of corneal perforation after oral administration of nonsteroidal anti-inflammatory drugs: oral NSAID-induced corneal damage.

    Science.gov (United States)

    Masuda, Ikuya; Matsuo, Toshihiko; Okamoto, Kazuo; Matsushita, Kyoko; Ohtsuki, Hiroshi

    2010-01-01

    To report 2 cases of corneal perforation associated with the use of oral nonsteroidal anti-inflammatory drugs (NSAIDs). In a 62-year-old woman and a 79-year-old woman, corneal perforation occurred after 7 days and 5 months of oral NSAIDs administration, respectively. After NSAIDs were discontinued, the cornea epithelialized and the anterior chamber formed within 14 and 10 days, respectively. It is well known that topical NSAIDs cause corneal perforation. Observations in the present cases suggest that the oral administration of NSAIDs may also cause corneal damage, and hence, medical professionals should consider the risk of damage to the cornea when administering these drugs orally.

  16. Enhanced oral bioavailability of docetaxel in rats combined with myricetin: In situ and in vivo evidences.

    Science.gov (United States)

    Hao, Tianyun; Ling, Yunni; Wu, Meijuan; Shen, Yajing; Gao, Yu; Liang, Shujun; Gao, Yuan; Qian, Shuai

    2017-04-01

    The purpose of this study was to investigate the effect of myricetin on the pharmacokinetics of docetaxel in rats. In comparison to oral docetaxel alone (40mg/kg), the bioavailability of docetaxel could be significantly enhanced by 1.6-2.4-fold via oral co-administration with various flavonoids (apigenin, naringenin, baicalein, quercetin and myricetin) at a dosage of 10mg/kg, and myricetin showed the highest bioavailability improvement. Further pharmacokinetic studies demonstrated that the presence of myricetin (5-20mg/kg) enhanced both C max and AUC of docetaxel with the highest C max (162ng/mL, 2.3-fold) and relative bioavailability (244%) achieved at 10mg/kg of myricetin, while t 1/2 was not influenced. In order to explore the reasons for such bioavailability enhancement of docetaxel, rat in situ single-pass intestinal perfusion model and intravenous docetaxel co-administrated with oral myricetin were carried out. After combining with myricetin, the permeability coefficient (P blood ) of docetaxel based on its appearance in mesenteric blood was significantly increased up to 3.5-fold in comparison to that of docetaxel alone. Different from oral docetaxel, the intravenous pharmacokinetics of docetaxel was not affected by co-administration of myricetin, indicating the limited effect of myricetin on the elimination of docetaxel. The above findings suggested that the oral bioavailability enhancement of docetaxel via co-administration with myricetin might be mainly attributed to the enhanced absorption in gastrointestinal tract rather than modulating the elimination of docetaxel. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Prevention of diet-induced obesity in rats by oral application of collagen fragments

    Directory of Open Access Journals (Sweden)

    Raksha Nataliia G.

    2018-01-01

    Full Text Available The aim of the present study was to determine whether orally applied collagen fragments (CFs could affect the development of obesity in obese rats. To this end, experimental rats that were exposed to a high-calorie diet (HCD for four weeks were randomly divided into two groups: HCD and HCD+CFs, with both groups continuing to receive the HCD. However, rats from the HCD+CFs group were also provided with CFs in a 0.05-M citrate buffer (pH 5.0 (1 g·kg-1 of body weight by intragastric administration, every other day for the next six weeks. Selected parameters associated with obesity development and insulin resistance, as well as serum markers of oxidative stress and the cytokine profile were assessed at the end of the 10th week. Supplementation with CFs resulted in a decrease in body weight and body mass index when compared to animals exposed to a HCD. The observed changes were assumed to be caused by a lower food intake and increased water intake by obese rats treated with CFs. Enhanced activity of superoxide dismutase (SOD, catalase (CAT and decreased malondialdehyde (MDA concentration were detected in the HCD+CF group of animals when compared to untreated HCD-fed rats. Administration of CFs also lowered the serum concentrations of the proinflammatory cytokines IL-1β and IL-12, whereas the concentration of the anti-inflammatory cytokine IL-10 was significantly increased and the concentration of cytokine IL-4 was near the control value. Decreased concentrations of fasting blood glucose, glycated hemoglobin (GHbA1c and serum insulin and increased tolerance to glucose in the oral glucose tolerance test (OGTT were observed in the HCD+CF group of animals when compared to rats in the HCD group. We concluded that CFs mediated a therapeutic effect on obesity development in rats exposed to a HCD by affecting pathways involved in obesity pathogenesis.

  18. Protective effects of orally applied fullerenol nano particles in rats after a single dose of doxorubicin

    Directory of Open Access Journals (Sweden)

    Ičević Ivana Đ.

    2011-01-01

    Full Text Available Polyhydroxylated, water soluble, fullerenol C60(OH24 nano particles (FNP in vitro and in vivo models, showed an expressive biological activity. The goal of this work was to investigate the potential protective effects of orally applied FNP on rats after a single dose of doxorubicin (DOX (8 mg/kg (i.p. 6 h after the last application of FNP. After the last drug administration, the rats were sacrificed, and the blood and tissues were taken for the analysis. Biochemical and pathological results obtained in this study indicate that fullerenol (FNP, in H2O:DMSO (80:20, w/w solution given orally in final doses of 10, 14.4, and 21.2 mg/kg three days successively, has the protective (hepatoprotective and nephroprotective effect against doxorubicin-induced cytotoxicity via its antioxidant properties.

  19. Dissolution and bioavailability enhancement of alpha-asarone by solid dispersions via oral administration.

    Science.gov (United States)

    Deng, Li; Wang, Yu; Gong, Tao; Sun, Xun; Zhang, Zhi-Rong

    2017-11-01

    Alpha (α)-asarone (1-propenyl-2,4,5-methoxybenzol) (ARE) has been extensively used to treat chronic obstructive pulmonary diseases (COPD), bronchial asthma, pneumonia, and epilepsy. Due to its poor solubility and bioavailability, ARE was clinically administered via intravenous injection. However, severe allergies were often reported due to the presence of solublizers in the injection formulation. In our study, we sought to explore the biopharmaceutical classification of ARE, elucidate the mechanisms behind ARE absorption, and to develop a viable formulation to improve the oral bioavailability of ARE. ARE was not a P-glycoprotein substrate, which was absorbed in the passive mode without site specificity in the gastrointestinal tract. Solid dispersions prepared using hydrophilic matrix materials such as Pluronic F68, and polyethylene glycol (PEG) of varying molecular weights (PEG4K, PEG10K, and PEG20K) were proven to significantly improve the dissolution of ARE in vitro and the oral bioavailability of ARE in rats, which represent a promising strategy for the oral administration of ARE and other BCS II compounds.

  20. Metabolic fate of poly-(lactic-co-glycolic acid)-based curcumin nanoparticles following oral administration.

    Science.gov (United States)

    Harigae, Takahiro; Nakagawa, Kiyotaka; Miyazawa, Taiki; Inoue, Nao; Kimura, Fumiko; Ikeda, Ikuo; Miyazawa, Teruo

    2016-01-01

    Curcumin (CUR), the main polyphenol in turmeric, is poorly absorbed and rapidly metabolized following oral administration, which severely curtails its bioavailability. Poly-(lactic-co-glycolic acid)-based CUR nanoparticles (CUR-NP) have recently been suggested to improve CUR bioavailability, but this has not been fully verified. Specifically, no data are available about curcumin glucuronide (CURG), the major metabolite of CUR found in the plasma following oral administration of CUR-NP. Herein, we investigated the absorption and metabolism of CUR-NP and evaluated whether CUR-NP improves CUR bioavailability. Following oral administration of CUR-NP in rats, we analyzed the plasma and organ distribution of CUR and its metabolites using high-performance liquid chromatography-tandem mass spectrometry. To elucidate the mechanism of increased intestinal absorption of CUR-NP, we prepared mixed micelles comprised of phosphatidylcholine and bile salts and examined the micellar solubility of CUR-NP. Additionally, we investigated the cellular incorporation of the resultant micelles into differentiated Caco-2 human intestinal cells. Following in vivo administration of CUR-NP, CUR was effectively absorbed and present mainly as CURG in the plasma which contained significant amounts of the metabolite compared with other organs. Thus, CUR-NP increased intestinal absorption of CUR rather than decreasing metabolic degradation and conversion to other metabolites. In vitro, CUR encapsulated in CUR-NP was solubilized in mixed micelles; however, whether the micelles contained CUR or CUR-NP had little influence on cellular uptake efficiency. Therefore, we suggest that the high solubilization capacity of CUR-NP in mixed micelles, rather than cellular uptake efficiency, explains the high intestinal absorption of CUR-NP in vivo. These findings provide a better understanding of the bioavailability of CUR and CUR-NP following oral administration. To improve the bioavailability of CUR, future

  1. Metabolic fate of poly-(lactic-co-glycolic acid-based curcumin nanoparticles following oral administration

    Directory of Open Access Journals (Sweden)

    Harigae T

    2016-06-01

    Full Text Available Takahiro Harigae,1 Kiyotaka Nakagawa,1 Taiki Miyazawa,2 Nao Inoue,3 Fumiko Kimura,1 Ikuo Ikeda,3 Teruo Miyazawa4,5 1Food and Biodynamic Chemistry Laboratory, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan; 2Vascular Biology Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA; 3Laboratory of Food and Biomolecular Science, Graduate School of Agricultural Science, 4Food and Biotechnology Innovation Project, New Industry Creation Hatchery Center, 5Food and Health Science Research Unit, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan Purpose: Curcumin (CUR, the main polyphenol in turmeric, is poorly absorbed and rapidly metabolized following oral administration, which severely curtails its bioavailability. Poly-(lactic-co-glycolic acid-based CUR nanoparticles (CUR-NP have recently been suggested to improve CUR bioavailability, but this has not been fully verified. Specifically, no data are available about curcumin glucuronide (CURG, the major metabolite of CUR found in the plasma following oral administration of CUR-NP. Herein, we investigated the absorption and metabolism of CUR-NP and evaluated whether CUR-NP improves CUR bioavailability.Methods: Following oral administration of CUR-NP in rats, we analyzed the plasma and organ distribution of CUR and its metabolites using high-performance liquid chromatography-tandem mass spectrometry. To elucidate the mechanism of increased intestinal absorption of CUR-NP, we prepared mixed micelles comprised of phosphatidylcholine and bile salts and examined the micellar solubility of CUR-NP. Additionally, we investigated the cellular incorporation of the resultant micelles into differentiated Caco-2 human intestinal cells.Results: Following in vivo administration of CUR-NP, CUR was effectively absorbed and present mainly as CURG in the plasma which contained significant amounts of the metabolite compared with

  2. Administration of dried Aloe vera gel powder reduced body fat mass in diet-induced obesity (DIO) rats.

    Science.gov (United States)

    Misawa, Eriko; Tanaka, Miyuki; Nabeshima, Kazumi; Nomaguchi, Kouji; Yamada, Muneo; Toida, Tomohiro; Iwatsuki, Keiji

    2012-01-01

    The aim of the present study was to investigate the anti-obesity effects of Aloe vera gel administration in male Sprague-Dawley (SD) rats with diet-induced obesity (DIO). SD rats at 7 wk of age were fed either a standard diet (10 kcal% fat) (StdD) or high-fat (60 kcal% fat) diet (HFD) during the experimental period. Four weeks after of HFD-feeding, DIO rats (11 wk of age) were orally administered with two doses of Aloe vera gel powder (20 and 200 mg/kg/d) for 90 d. Body weights (g) and body fat (%) of HFD fed rats were significantly higher than those of StdD-fed rats. Although a modest decrease of body weight (g) was observed with the administration of dried Aloe vera gel powder, both subcutaneous and visceral fat weight (g) and body fat (%) were reduced significantly in Aloe vera gel-treated rats. Serum lipid parameters elevated by HFD were also improved by the Aloe vera gel treatment. The oxygen consumption (VO(2)), an index of energy expenditure, was decreased in HFD-fed rats compared with that in StdD-fed rats. Administration of Aloe vera gel reversed the change in VO(2) in the HFD-fed rats. These results suggest that intake of Aloe vera gel reduced body fat accumulation, in part, by stimulation of energy expenditure. Aloe vera gel might be beneficial for the prevention and improvement of diet-induced obesity.

  3. Tissue distribution and excretion kinetics of orally administered silica nanoparticles in rats

    Science.gov (United States)

    Lee, Jeong-A; Kim, Mi-Kyung; Paek, Hee-Jeong; Kim, Yu-Ri; Kim, Meyoung-Kon; Lee, Jong-Kwon; Jeong, Jayoung; Choi, Soo-Jin

    2014-01-01

    Purpose The effects of particle size on the tissue distribution and excretion kinetics of silica nanoparticles and their biological fates were investigated following a single oral administration to male and female rats. Methods Silica nanoparticles of two different sizes (20 nm and 100 nm) were orally administered to male and female rats, respectively. Tissue distribution kinetics, excretion profiles, and fates in tissues were analyzed using elemental analysis and transmission electron microscopy. Results The differently sized silica nanoparticles mainly distributed to kidneys and liver for 3 days post-administration and, to some extent, to lungs and spleen for 2 days post-administration, regardless of particle size or sex. Transmission electron microscopy and energy dispersive spectroscopy studies in tissues demonstrated almost intact particles in liver, but partially decomposed particles with an irregular morphology were found in kidneys, especially in rats that had been administered 20 nm nanoparticles. Size-dependent excretion kinetics were apparent and the smaller 20 nm particles were found to be more rapidly eliminated than the larger 100 nm particles. Elimination profiles showed 7%–8% of silica nanoparticles were excreted via urine, but most nanoparticles were excreted via feces, regardless of particle size or sex. Conclusion The kidneys, liver, lungs, and spleen were found to be the target organs of orally-administered silica nanoparticles in rats, and this organ distribution was not affected by particle size or animal sex. In vivo, silica nanoparticles were found to retain their particulate form, although more decomposition was observed in kidneys, especially for 20 nm particles. Urinary and fecal excretion pathways were determined to play roles in the elimination of silica nanoparticles, but 20 nm particles were secreted more rapidly, presumably because they are more easily decomposed. These findings will be of interest to those seeking to predict

  4. Oral carcinogenicity study with nickel sulfate hexahydrate in Fischer 344 rats

    International Nuclear Information System (INIS)

    Heim, Katherine E.; Bates, Hudson K.; Rush, Rusty E.; Oller, Adriana R.

    2007-01-01

    Until now, existing data on the oral carcinogenicity of nickel substances have been inconclusive. Yet, the assessment of oral carcinogenicity of nickel has serious scientific and regulatory implications. In the present study, nickel sulfate hexahydrate was administered daily to Fischer 344 rats by oral gavage for 2 years (104 weeks) at exposure levels of 10, 30 and 50 mg NiSO 4 ·6H 2 O/kg. This treatment produced a statistically significant reduction in body weight of male and female rats, compared to controls, in an exposure-related fashion at 30 and 50 mg/kg/day. An exposure-dependent increase in mortality was observed in female rats. However, the overall study survival rate (males and females) was at least 25 animals per group (compliant with OECD guidelines) in the treated animals. Daily oral administration of nickel sulfate hexahydrate did not produce an exposure-related increase in any common tumor type or an increase in any rare tumors. One tumor type was statistically increased in a nickel sulfate-treated group compared to the study controls (keratoacanthoma in the 10 mg NiSO 4 ·6H 2 O/kg/day males), but there was no exposure-response relationship for this common tumor type. This study achieved sufficient toxicity to reach the Maximum Tolerated Dose (MTD) while maintaining a sufficiently high survival rate to allow evaluation for carcinogenicity. The present study indicated that nickel sulfate hexahydrate does not have the potential to cause carcinogenicity by the oral route of exposure in the Fischer 344 rat. Data from this and other studies demonstrate that inhalation is the only route of exposure that might cause concern for cancer in association with nickel exposures

  5. A Rapid Centrifugation-Assisted Solid-Phase Extraction and Liquid Chromatography Method for Determination of Loureirin A and Loureirin B of Dragon's Blood Capsules in Rat Plasma and Urine After Oral Administration.

    Science.gov (United States)

    Chen, Xiaoshuang; Li, Gaofeng; Ma, Shangfang; Hu, Xujia

    2015-07-01

    A simple, sensitive and rapid centrifugation-assisted solid-phase extraction (SPE) with high-performance liquid chromatography (SPE-HPLC) method was developed for simultaneous determination of the metabolites loureirin A and loureirin B from Dragon's blood in rat plasma and urine. The development of the extraction procedure included optimization of some important extraction phases. After evaluation, the metabolites of Dragon's blood were extracted by centrifugation-assisted SPE and separated by using HPLC. This method showed good linearity (r(2) > 0.99), and in the rat plasma and urine, the recoveries were 93.1 and 95.7% for loureirin A and were 90.1 and 94.2% for loureirin B. The relative standard deviation (RSD) values of intraday and interday precision in rat plasma and urine for loureirin A were <3.84 and 2.01%, respectively. The RSD values of the intraday and interday precision in rat plasma and urine for loureirin B were below 4.25 and 5.83%, respectively. Thus, the established method is suitable for metabolism studies of loureirin A and loureirin B in rat plasma and urine. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  6. Comparative chlorpyrifos pharmacokinetics via multiple routes of exposure and vehicles of administration in the adult rat

    International Nuclear Information System (INIS)

    Smith, Jordan Ned; Campbell, James A.; Busby-Hjerpe, Andrea L.; Lee, Sookwang; Poet, Torka S.; Barr, Dana B.; Timchalk, Charles

    2009-01-01

    Chlorpyrifos (CPF) is a commonly used organophosphorus pesticide. A number of toxicity and mechanistic studies have been conducted in animals, where CPF has been administered via a variety of different exposure routes and dosing vehicles. This study compared chlorpyrifos (CPF) pharmacokinetics using oral, intravenous (IV), and subcutaneous (SC) exposure routes and corn oil, saline/Tween 20, and dimethyl sulfoxide (DMSO) as dosing vehicles. Two groups of rats were co-administered target doses (5 mg/kg) of CPF and isotopically labeled CPF (L-CPF). One group was exposed by both oral (CPF) and IV (L-CPF) routes using saline/Tween 20 vehicle; whereas, the second group was exposed by the SC route using two vehicles, corn oil (CPF) and DMSO (L-CPF). A third group was only administered CPF by the oral route in corn oil. For all treatments, blood and urine time course samples were collected and analyzed for 3,5,6-trichloro-2-pyridinol (TCPy), and isotopically labeled 3,5,6-trichloro-2-pyridinol (L-TCPy). Peak TCPy/L-TCPy concentrations in blood (20.2 μmol/l), TCPy/L-TCPy blood AUC (94.9 μmol/l h), and percent of dose excreted in urine (100%) were all highest in rats dosed orally with CPF in saline/Tween 20 and second highest in rats dosed orally with CPF in corn oil. Peak TCPy concentrations in blood were more rapidly obtained after oral administration of CPF in saline/Tween 20 compared to all other dosing scenarios (>1.5 h). These results indicate that orally administered CPF is more extensively metabolized than systemic exposures of CPF (SC and IV), and vehicle of administration also has an effect on absorption rates. Thus, equivalent doses via different routes and/or vehicles of administration could potentially lead to different body burdens of CPF, different rates of bioactivation to CPF-oxon, and different toxic responses. Simulations using a physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model for CPF are consistent with these possibilities

  7. Serum protein and enzyme levels in rats following administration of ...

    African Journals Online (AJOL)

    The effects of caffeinated and non-caffeinated paracetamol administration, with or without vitamins A and E supplementation on the protein and enzyme levels in Wistar albino rats were investigated using cafeinated paracetamol and paracetamol as caffeinated and non-caffeinated paracetamol respectively, and water ...

  8. Simultaneous Determination of Bergapten, Imperatorin, Notopterol, and Isoimperatorin in Rat Plasma by High Performance Liquid Chromatography with Fluorescence Detection and Its Application to Pharmacokinetic and Excretion Study after Oral Administration of Notopterygium incisum Extract

    Directory of Open Access Journals (Sweden)

    John Teye Azietaku

    2016-01-01

    Full Text Available A specific, sensitive, and reliable high performance liquid chromatography with fluorescence detection (HPLC-FLD was first optimized and then used in the simultaneous quantification of bergapten, imperatorin, notopterol, and isoimperatorin in rat plasma using osthole as the internal standard. Liquid-liquid extraction with ethyl acetate was employed in treating the rat plasma samples obtained. Separation was carried out with a Hedera™ ODS column (4.6 × 250 mm, 5 μm by gradient elution at a temperature of 40°C. Excitation and emission of the fluorescence detector were set to 300 and 490 nm, respectively. The lower limits of quantification for bergapten, imperatorin, notopterol, and isoimperatorin in rat plasma were 4, 40, 4, and 2 ng mL−1, respectively. The intraday and interday precision and accuracy for the four coumarins were within acceptable criteria. The recovery of the method was satisfactory with a range of 80.3–114%. The validated method was successfully used for the simultaneous determination of the four coumarins in Notopterygium incisum extracts and also for the pharmacokinetic and excretion study of bergapten, imperatorin, notopterol, and isoimperatorin in rats.

  9. Effect of Apium graveolens Extract Administration on the Pharmacokinetics of Captopril in the Plasma of Rats

    Directory of Open Access Journals (Sweden)

    Siska Siska

    2018-02-01

    Full Text Available Apium graveolens (celery is an edible and traditionally medicinal plant that is used worldwide, among others for the treatment of hypertension. Combining celery with antihypertensive drugs can affect the pharmacodynamics and pharmacokinetics of the latter drugs. The aim of the study is to assess the effects of administrating the celery extract on captopril pharmacokinetics. Sprague-Dawley strain rats were divided into two groups (n = 6. Group I was given captopril (10 mg/kg Body Weight (BW orally, while Group II was pretreated with celery extract orally (40 mg/kg BW an hour before administration of captopril. The blood samples were withdrawn at various intervals after drug administration. The captopril concentration was determined using liquid chromatography–mass spectrometry (LC-MS/MS and from the blood data, the values of Ke, Cmax, Tmax, T1/2, and area under the curve (AUC were calculated. The results showed that oral administration of the celery extract increased Cmax (38.67%, T1/2 (37.84%, and AUC (58.10% and decreased Ke (27.45% of captopril in Group II (celery + captopril compared with Group I (captopril. In conclusion, celery extract can alter the pharmacokinetic of captopril when given in combination. The combination might be beneficial for the treatment of hypertension, as celery causes an increase in the plasma level of captopril, which can enhance its efficacy.

  10. Administrative Challenges to the Integration of Oral Health With Primary Care

    Science.gov (United States)

    Maxey, Hannah L.; Randolph, Courtney; Gano, Laura; Kochhar, Komal

    2017-01-01

    Inadequate access to preventive oral health services contributes to oral health disparities and is a major public health concern in the United States. Federally Qualified Health Centers play a critical role in improving access to care for populations affected by oral health disparities but face a number of administrative challenges associated with implementation of oral health integration models. We conducted a SWOT (strengths, weaknesses, opportunities, and threats) analysis with health care executives to identify strengths, weaknesses, opportunities, and threats of successful oral health integration in Federally Qualified Health Centers. Four themes were identified: (1) culture of health care organizations; (2) operations and administration; (3) finance; and (4) workforce. PMID:27218701

  11. Oral administration of fisetin promotes the induction of hippocampal long-term potentiation in vivo.

    Science.gov (United States)

    He, Wen-Bin; Abe, Kazuho; Akaishi, Tatsuhiro

    2018-01-01

    To explore memory enhancing effect of the flavonoid fisetin, we investigated the effect of oral administration of flavonoids on the induction of long-term potentiation (LTP) at hippocampal CA1 synapses of anesthetized rats. Among four flavonoids (fisetin, quercetin, luteolin and myricetin) tested, only fisetin significantly facilitated the induction of hippocampal LTP. The effect of oral fisetin was abolished by intracerebroventricular injection of U0126, an agent that was previously found to inhibit its effect in hippocampal slices in vitro. These results suggest that orally administered fisetin crosses the blood-brain barrier and promotes synaptic functions in the hippocampus. Copyright © 2018 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  12. Behavioral and neurochemical effects of chronic administration of reserpine and SKF-38393 in rats

    International Nuclear Information System (INIS)

    Neisewander, J.L.; Lucki, I.; McGonigle, P.

    1991-01-01

    Alterations in the density of dopamine receptor subtypes and behaviors mediated by the D1-selective agonist SKF-38393 were examined in rats treated chronically with reserpine, SKF-38393 or the combination of these drugs. Animals received either vehicle or reserpine (1 mg/kg s.c.) on days 1 to 28 and, in addition, half of each of these groups were treated with vehicle and half were treated with SKF-38393 (5-10 mg/kg s.c.) on days 15 to 29. Quantitative autoradiographic measurement of D1 receptors labeled with [ 3 H]SCH-23390 and D2 receptors labeled with [ 3 H]spiroperidol revealed that chronic administration of reserpine increased the density of both receptor subtypes in the nucleus accumbens and caudate-putamen, but not in the substantia nigra. Chronic administration of SKF-38393 alone did not alter D1 receptor density in any of these regions. However, chronic administration of the agonist in reserpinized animals decreased D1 receptor density in the nucleus accumbens, but not in the caudate-putamen or substantia nigra, demonstrating that this partial agonist can selectively down-regulate D1 receptors when endogenous dopaminergic tone is removed. The chronic drug treatments also altered behavioral responses. Chronic administration of SKF-38393 alone produced sensitization of the oral dyskinesia response elicited by a challenge injection of the agonist, but no significant change in the grooming response. Acute administration of SKF-38393 in rats treated with reserpine for 14 days produced stereotypy which was not altered after chronic administration of the agonist. Surprisingly, chronic administration of reserpine alone produced a spontaneous oral dyskinesia, which was blocked dose-dependently by the D2-selective antagonist spiroperidol. These findings are discussed in terms of their relevance to Parkinson's disease and tardive dyskinesia

  13. A comparative pharmacokinetic study of three flavonoids and three anthraquinones in normal and gastrointestinal motility disorders rat plasma after the oral administration of Wei-Chang-Shu tablet using high-performance liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Ren, Yan; Zhao, Weiwei; Zhao, Juanjuan; Chen, Xiangming; Yu, Chen; Liu, Mengan

    2017-11-01

    A simple, fast and reliable high-performance liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous quantification and pharmacokinetic study of three flavonoids (liquiritigenin, isoliquiritigenin and formononetin) and three anthraquinones (emodin, rhein and aloe-emodin), which are the bioactive ingredients of Wei-Chang-Shu tablet found in rat plasma. After extraction by liquid-liquid extraction with ethyl acetate, chromatographic separation was achieved on an Agilent Zorbax SB-C 18 column (4.6 × 150 mm, 5 μm) at a flow rate of 1 mL/min by gradient elution using 0.1% aqueous acetic acid and acetonitrile. The detection was performed using a triple quadrupole mass spectrometer equipped with electrospray ionization source in the negative ionization and selected reaction monitoring mode. Method validation was performed in terms of specificity, carryover, linearity (r > 0.99), intra-/inter-day precision (1.0-10.1%), accuracy (relative error, <7.6%), stability (0.6-13.2%), extract recovery (74.9-91.9%) and matrix effect (89.1-109%). The lower limits of quantification of the six analytes varied from 0.92 to 10.4 ng/mL. The validated method was successfully applied to compare the pharmacokinetic properties of Wei-Chang-Shu tablet in normal rats and in rats with gastrointestinal motility disorders. The results indicated that there were obvious differences in the pharmacokinetic behavior between normal and model rats. This study will be helpful in the clinical application of Wei-Chang-Shu tablet. Copyright © 2017 John Wiley & Sons, Ltd.

  14. A C8-Modified Graphene@mSiO2 Composites Based Method for Quantification of Gallic Acid in Rat Plasma after Oral Administration of Changtai Granule and Its Application to Pharmacokinetics.

    Science.gov (United States)

    Xu, Chen; Yu, Yingjia; Ling, Li; Wang, Yang; Zhang, Jundong; Li, Yan; Duan, Gengli

    2017-01-01

    A rapid, effective extraction technique has been established for measuring the gallic acid in rat plasma by using sandwich-structured graphene/mesoporous silica composites with C 8 -modified interior pore-walls as adsorbent. The unique characteristics of the graphene-silica composites excluded large molecules, like proteins, from the mesopore channels as a result of size exclusion effect, leading to a direct extraction of drug molecules from protein-rich biological samples such as plasma without any other pretreatment procedure. Followed by elution and centrifugation, the gallic acid-absorbed composites were rapidly isolated before LC-MS/MS. Serving as a reliable tool for analysis of Traditional Chinese Medicine: Changtai Granule, the newly developed method was fully validated and successfully applied in the pharmacokinetic study of gallic acid in rat plasma. Extraction recovery, matrix effect and stability were satisfactory in rat plasma. According to the results of pharmacokinetic studies, Changtai Granule exhibited greater adsorption, distribution and clearance properties of gallic acid in the treatment of ulcerative colitis. Hence, this study may offer a valuable alternative to simplify and speed up sample preparation, and be useful for clinical studies of related preparations.

  15. The in vivo situation of 3H-Aescin which had been administered orally and subcutaneously to rats

    International Nuclear Information System (INIS)

    Suga, Tetsuya; Matsumoto, Yoshio; Hayase, Shigeru.

    1975-01-01

    The in vivo situation of the Aescin, a product of aesculus hippocastanum, was examined by administering the 3 H labelled compounds to rats. The following results were obtained: 1) The intestinal absorption from oral administration was not so fast. The blood concentration was low, and its combination with plasma protein was slight. 2) As for the distribution in the organs after an oral administration, the affinity was relatively high in the following organs: Pancreas>heart>kidney>adrenal>gland>lung>muscle>liver. However, the concentrations were extremely low being shown by a ng unit per g tissue in the organs. 3) When it was administered orally to the pregnant rats, the concentrations which were transmitted to the fetuses were low. 4) On the 7th day after oral administration, excretion into the urine was less than 3% and in the feces was more than 70%. The bile excretion was also observed. 5) The metabolic products in the excretion after the oral administration were examined by the method. A large amount of Aescin was excreted in an unchanged form or in compounds. From this, Aescin is presumed to be metabolised by the activity of intestinal bacterial enzymes. 6) The absorption of this drug into the body was low when it was intracutaneously administered. (Saito, K.)

  16. In vivo situation of /sup 3/H-Aescin which had been administered orally and subcutaneously to rats

    Energy Technology Data Exchange (ETDEWEB)

    Suga, T; Matsumoto, Y [Tokyo Coll. of Pharmacy (Japan); Hayase, S

    1975-08-01

    The in vivo situation of the Aescin, a product of aesculus hippocastanum, was examined by administering the /sup 3/H labelled compounds to rats. The following results were obtained: (1) The intestinal absorption from oral administration was not so fast. The blood concentration was low, and its combination with plasma protein was slight. (2) As for the distribution in the organs after an oral administration, the affinity was relatively high in the following organs: Pancreas(3)heart>kidney>adrenal>gland>lung>muscle>liver. However, the concentrations were extremely low being shown by a ng unit per g tissue in the organs. 3) When it was administered orally to the pregnant rats, the concentrations which were transmitted to the fetuses were low. (4) On the 7th day after oral administration, excretion into the urine was less than 3% and in the feces was more than 70%. The bile excretion was also observed. (5) The metabolic products in the excretion after the oral administration were examined by the method. A large amount of Aescin was excreted in an unchanged form or in compounds. From this, Aescin is presumed to be metabolised by the activity of intestinal bacterial enzymes. (6) The absorption of this drug into the body was low when it was intracutaneously administered.

  17. The pharmacokinetics of L-tryptophan following its intravenous and oral administration.

    OpenAIRE

    Green, A R; Aronson, J K; Cowen, P J

    1985-01-01

    The pharmacokinetics of L-tryptophan (5 g and 7.5 g) have been studied after its intravenous administration to healthy subjects and the results compared with those obtained after oral administration (0.7 g-3.5 g). In order to do this, we have re-analysed previously published data relating to oral administration. The data obtained following the oral administration of L-tryptophan suggest that the total body clearance and apparent volume of distribution are saturable. The pharmacokinetics of tr...

  18. Improved oral bioavailability in rats of SR13668, a novel anti-cancer agent.

    Science.gov (United States)

    Green, Carol E; Swezey, Robert; Bakke, James; Shinn, Walter; Furimsky, Anna; Bejugam, Naveen; Shankar, Gita N; Jong, Ling; Kapetanovic, Izet M

    2011-05-01

    SR13668, a bis-indole with potent activity in vitro and in vivo against various cancers and promising cancer chemopreventive activity, was found to have very low oral bioavailability, <1%, in rats during pilot pharmacokinetic studies. The objective of these studies was to better understand the source of low oral exposure and to develop a formulation that could be used in preclinical development studies. An automated screening system for determining solubility in lipid-based vehicles, singly and in combination, was used to identify formulations that might enhance absorption by improving solubility of SR13668, and these results were confirmed in vivo using Sprague-Dawley rats. Pharmacokinetics of SR13668 was then determined in male and female Sprague-Dawley rats administered 1 mg/kg iv, 1, 10, and 30 mg/kg po formulated in PEG400:Labrasol (1:1 v/v). Blood was collected at time points through 24 h and the concentration of SR13668 determined using HPLC with UV and fluorescence detection. SR13668 was found to be resistant to plasma esterases in vitro and relatively stable to rat and human liver microsomal metabolism. SR13668 concentrates in tissues as indicated by significantly higher levels in lung compared to blood, blood concentrations ~2.5-fold higher than plasma levels, and apparent volume of distribution (V) of ~5 l/kg. A marked sex difference was observed in exposure to SR13668 with area under the curve (AUC) significantly higher and clearance (CL) lower for female compared to male rats, after both iv and oral administration. The oral bioavailability (F) of SR13668 was 25.4 ± 3.8 and 27.7 ± 3.9% (30 mg/kg), for males and females, respectively. A putative metabolite (M1), molecular weight of 445 in the negative ion mode (i.e., SR13668 + 16), was identified in blood samples from both the iv and po routes, as well as in vitro microsomal samples. In summary, while SR13668 does undergo metabolism, probably by the liver, the oral bioavailability of SR13668 in rats

  19. Repeated oral administration of capsaicin increases anxiety-like ...

    Indian Academy of Sciences (India)

    2013-07-22

    Jul 22, 2013 ... open arms was reduced in capsaicin-treated rats compared with control rats. In forced ... TRPV1 receptors was also observed in the prefrontal cortex, nucleus ... its implication in the control of psycho-motor activities. Indeed ...

  20. Disintegration of chemotherapy tablets for oral administration in patients with swallowing difficulties.

    Science.gov (United States)

    Siden, Rivka; Wolf, Matthew

    2013-06-01

    The administration of oral chemotherapeutic drugs can be problematic in patients with swallowing difficulties. Inability to swallow solid dosage forms can compromise compliance and may lead to poor clinical outcome. The current technique of tablet crushing to aid in administration is considered an unsafe practice. By developing a technique to disintegrate tablets in an oral syringe, the risk associated with tablet crushing can be avoided. The purpose of this study was to determine the feasibility of using disintegration in an oral syringe for the administration of oral chemotherapeutic tablets. Eight commonly used oral chemotherapeutic drugs were tested. Tablets were placed in an oral syringe and allowed to disintegrate in tap water. Various volumes and temperatures were tested to identify which combination allows for complete disintegration of the tablet in the shortest amount of time. The oral syringe disintegration method was considered feasible if disintegration occurred in ≤15 min and in ≤20 mL of water and the dispersion passed through an oral syringe tip. The following tablets were shown to disintegrate within 15 min and in disintegration test. Disintegrating oral chemotherapeutic tablets in a syringe provides a closed system to administer hazardous drugs and allows for the safe administration of oral chemotherapeutic drugs in a tablet form to patients with swallowing difficulties.

  1. Acute and sub-acute oral toxicity of Dracaena cinnabari resin methanol extract in rats.

    Science.gov (United States)

    Al-Afifi, Nashwan Abdullah; Alabsi, Aied Mohammed; Bakri, Marina Mohd; Ramanathan, Anand

    2018-02-05

    Dracaena cinnabari (DC) is a perennial tree that located on the Southern coast of Yemen native to the Socotra Island. This tree produces a deep red resin known as the Dragon's blood, the Twobrother's Blood or Damm Alakhwain. The current study performed to evaluate the safety of the DC resin methanol extract after a single or 28 consecutive daily oral administrations. In assessing the safety of DC resin methanol extract, acute and sub-acute oral toxicity tests performed following OECD guidelines 423 and 407, respectively, with slight modifications. In acute oral toxicity test, DC resin methanol extract administered to female Sprague Dawley rats by oral gavage at a single dose of 300 and 2000 mg/kg body weight. Rats observed for toxic signs for 14 days. In sub-acute oral toxicity test, DC resin methanol extract administered to the rats by oral gavage at 500, 1000, and 1500 mg/kg body weight daily up to 28 days to male and female Spradgue Dawley rats. The control and high dose in satellite groups were also maintained and handled as the previous groups to determine the late onset toxicity of DC resin methanol extract. At the end of each test, hematological and biochemical analysis of the collected blood were performed as well as gross and microscopic pathology. In acute oral toxicity, no treatment-related death or toxic signs were observed. It revealed that the DC resin methanol extract could be well tolerated up to the dose 2000 mg/kg body weight and could be classified as Category 5. The sub-acute test observations indicated that there are no treatment-related changes up to the high dose level compared to the control. Food consumption, body weight, organ weight, hematological parameters, biochemical parameters and histopathological examination (liver, kidney, heart, spleen and lung) revealed no abnormalities. Water intake was significantly higher in the DC resin methanol extract treated groups compared to the control. This study demonstrates tolerability of DC

  2. Ninety-day oral toxicity study of rice-derived γ-oryzanol in Sprague-Dawley rats

    Directory of Open Access Journals (Sweden)

    Seol-Hee Moon

    Full Text Available A 90-day oral toxicity study of γ-oryzanol, a rice-derived triterpenoid ferulate, was performed by oral gavage administration to male and female Sprague-Dawley rats at doses of 0, 1000, and 2000 mg/kg body weight/day. All rats administered γ-oryzanol survived throughout the study period. Both male and female rats showed no toxicologically significant changes of the general signs, examination findings, body weight, food consumption, functional observational battery results, ophthalmological findings, urinalysis, hematology tests, clinical chemistry tests, organ weights, and necropsy findings. Moreover, there were no histopathological changes related to administration of γ-oryzanol in males and females from the 2000 mg/kg body weight/day group. In conclusion, the no observed adverse effect level (NOAEL of γ-oryzanol exceeded 2000 mg/kg body weight/day for both male and female rats under the conditions of this study. Keywords: γ-Oryznaol, Rice, Rat, Repeated-dose oral toxicity study, NOAEL

  3. Effects of amphetamine administration on neurogenesis in adult rats

    Directory of Open Access Journals (Sweden)

    Tomasz Stępień

    2017-12-01

    Full Text Available In our study expression of phospho-(Ser-10-histone H3 (pH3S10, a marker for the early stage of neurogenesis, and cellular early response genes were investigated using c-Fos protein as an example of a transcription factor in the neurogenic process in rats. Neurogenesis in the adult brain is regulated by endo- and exogenous factors, which influence the proliferation potential of progenitor cells and accelerate the dendritic development of newborn neurons. D-amphetamine, a psychoactive substance, is one of the exogenous factors able to influence the process of neurogenesis. The rats were injected with D-amphetamine at a dose of 1.5 mg/kg/body weight (b.w. under one administration scheme. Analysis of the pH3S10 and c-Fos expression levels in the group of D-amphetamine administered rats provided evidence of enhanced expression of these proteins in the regions of neurogenesis occurrence in rats. However, conclusions concerning stimulant effects of amphetamine on neurogenesis should be formulated with great caution, taking into account amphetamine dosage and the administration scheme. It should also be remembered that doses of psychoactive substances used in animal models can be lethal to humans.

  4. Grape Seed oil as Anti hepatic and Anti renal Dysfunction agent in Paracetamol Administrated Rats

    International Nuclear Information System (INIS)

    Farag, M.F.; Osman, N.N.; Darwish, M.M.

    2010-01-01

    The protection conferred by dietary grape seed oil (GSO) against paracetamol (PCL)-induced liver and kidney dysfunction have been evaluated in adult male albino Wistar rats. The animals (180-200 g) were randomly divided into four groups of seven rats each. Group l: normal control, group II: animals received GSO (3.7 g Kg-1 body wt/day orally), group III: animals received PCL (4 g Kg-1 body wt/day orally) and group IV: animals received PCL plus GSO. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AP), gamma glutamyl transferase (GGT), urea (U), creatinine (Cr) and albumin (A) levels in serum and blood urea nitrogen (BUN) were measured. In addition, the levels of thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) and the activity of superoxide dismutase (SOD) and catalase (CAT) in the liver and kidney homogenates were chosen for assessing. The PCL induced a significant elevation in the serum AST, ALT, AP and GGT. Moreover, a significant increase in serum U, Cr, A and BUN were evident. Furthermore, a significant rise in TBARS, while a significant declined activity of SOD and CAT and GSH content in liver and kidney homogenates were also observed. Oral administration of GSO resulted in a significant reduction in liver and kidney markers in serum, BUN as well hepatic and renal TBARS accompanied by a significant improvement in the tissue antioxidants and A, when compared with PCL damaged rats. It was suggested that GSO has potent hepatic and renal protective effects against the oxidative damage induced in rats due to PCL treatment, perhaps by its antioxidative effects hence eliminating the deleterious effects of PCL.

  5. Influence of PEG coating on the oral bioavailability of gold nanoparticles in rats.

    Science.gov (United States)

    Alalaiwe, Ahmed; Roberts, Georgia; Carpinone, Paul; Munson, John; Roberts, Stephen

    2017-11-01

    Metallic nanoparticles can be produced in a variety of shapes, sizes, and surface chemistries, making them promising potential tools for drug delivery. Most studies to date have evaluated uptake of metallic nanoparticles from the GI tract with methods that are at best semi-quantitative. This study used the classical method of comparing blood concentration area under the curve (AUC) following intravenous and oral doses to determine the oral bioavailability of 1, 2 and 5 kDa PEG-coated 5 nm gold nanoparticles (AuNPs). Male rats were given a single intravenous dose (0.8 mg/kg) or oral (gavage) dose (8 mg/kg) of a PEG-coated AuNP, and the concentration of gold was measured in blood over time and in tissues (liver, spleen and kidney) at sacrifice. Blood concentrations following oral administration were inversely related to PEG size, and the AUC in blood was significantly greater for the 1 kDa PEG-coated AuNPs than particles coated with 2 or 5 kDa PEG. However, bioavailabilities of all of the particles were very low (bioavailability of AuNPs coated with PEG in the 1-5 kDa range, this study demonstrates the utility of applying the blood AUC approach to assess the quantitative oral bioavailability of metallic nanoparticles.

  6. Gut Microbiota-Regulated Pharmacokinetics of Berberine and Active Metabolites in Beagle Dogs After Oral Administration.

    Science.gov (United States)

    Feng, Ru; Zhao, Zhen-Xiong; Ma, Shu-Rong; Guo, Fang; Wang, Yan; Jiang, Jian-Dong

    2018-01-01

    Berberine (BBR) is considered a multi-target drug that has significant advantages. In contrast to its significant pharmacological effects in clinic, the plasma level of BBR is very low. Our previous work revealed that dihydroberberine (dhBBR) could be an absorbable form of BBR in the intestine, and butyrate is an active metabolite that is generated by gut bacteria in rats. In this study, for the first time we describe gut microbiota-regulated pharmacokinetics in beagle dogs after oral administration of BBR by single (50 mg/kg) or multiple doses (50 mg/kg/d) for 7 days. GC-MS, GC, LC-MS/MS, and LC/MS n -IT-TOF were used to detect dhBBR, butyrate and BBR as well as its Phase I and II metabolites, respectively. The results showed that dhBBR was not detected in dog plasma but was excreted in small amounts in the feces of dogs examined on days 3 and 7. Butyrate was generated by gut bacteria and increased by 1.3- and 1.2-fold in plasma or feces, respectively, after 7 days of BBR treatment compared to the levels before treatment. Changes of intestinal bacterial composition were analyzed by 16S rRNA genes analysis. The results presented that dogs treated with BBR for 7 days increased both the abundance of the butyrate- and the nitroreductases- producing bacteria. We also identified chemical structures of the Phase I and II metabolites and analyzed their contents in beagle dogs. Eleven metabolites were detected in plasma and feces after BBR oral administration (50 mg/kg) to dogs, including 8 metabolites of Phase I and III metabolites of Phase II. The pharmacokinetic profile indicated that the concentration of BBR in plasma was low, with a C max value of 36.88 ± 23.45 ng/mL. The relative content of glucuronic acid conjugates (M11) was higher than those of other metabolites (M1, M2, M12, and M14) in plasma. BBR was detected in feces, with high excreted amounts on day 3 (2625.04 ± 1726.94 μg/g) and day 7 (2793.43 ± 488.10 μg/g). In summary, this is the first study to

  7. Bioavailability and pharmacokinetics of oral and injectable formulations of methadone after intravenous, oral, and intragastric administration in horses.

    Science.gov (United States)

    Linardi, Renata L; Stokes, Ashley M; Keowen, Michael L; Barker, Steven A; Hosgood, Giselle L; Short, Charles R

    2012-02-01

    To characterize the bioavailability and pharmacokinetics of oral and injectable formulations of methadone after IV, oral, and intragastric administration in horses. 6 healthy adult horses. Horses received single doses (each 0.15 mg/kg) of an oral formulation of methadone hydrochloride orally or intragastrically or an injectable formulation of the drug orally, intragastrically, or IV (5 experimental treatments/horse; 2-week washout period between each experimental treatment). A blood sample was collected from each horse before and at predetermined time points over a 360-minute period after each administration of the drug to determine serum drug concentration by use of gas chromatography-mass spectrometry analysis and to estimate pharmacokinetic parameters by use of a noncompartmental model. Horses were monitored for adverse effects. In treated horses, serum methadone concentrations were equivalent to or higher than the effective concentration range reported for humans, without induction of adverse effects. Oral pharmacokinetics in horses included a short half-life (approx 1 hour), high total body clearance corrected for bioavailability (5 to 8 mL/min/kg), and small apparent volume of distribution corrected for bioavailability (0.6 to 0.9 L/kg). The bioavailability of methadone administered orally was approximately 3 times that associated with intragastric administration. Absorption of methadone in the small intestine in horses appeared to be limited owing to the low bioavailability after intragastric administration. Better understanding of drug disposition, including absorption, could lead to a more appropriate choice of administration route that would enhance analgesia and minimize adverse effects in horses.

  8. Possible Outcome of Fenugreek Seeds Powder Administration on the Fertility of Female and Male Albino Rat

    Energy Technology Data Exchange (ETDEWEB)

    Ibrahim, M F; El-Tawill, G.A., E-mail: gkyrillos@hotmail.co [Radiation Biology Department, National Centre for Radiation Research and Technology (NCRRT), Atomic Energy Authority, Cairo (Egypt)

    2010-07-01

    Fenugreek (Trigonella foenum-graecum) is an annual plant from the family of Papilionaceae-Leguminosae that has been credited with many medicinal properties. The current study aims to evaluate the possible fertility activity of fenugreek seeds powder on female and male albino rats. To achieve the theme, fenugreek seeds powder (200 mg/rat) were daily administered orally to both female and male Wistar rats for 15 and 30 consecutive days, after which the rats were sacrificed for both biochemical and histopathological observations. Fenugreek treatment significantly decreased the serum cholesterol levels in both female and male rats with a marked increase in the ovary and testis cholesterol levels following 30 days of consecutive administration. The circulating serum female hormones showed an initial elevation at the end of 15 days of fenugreek intake followed by a significant drop in the group of rats that continued to receive the daily fenugreek dose for 30 days. These observations were supported by the notable decline in the ovarian weights further validated by their ovarian histological sections revealing remarkable dissolution of some follicles and prominent abundance of inflammatory cells. In the 30 days interval treated males, the serum testosterone hormone concentrations significantly declined and the testis weights were reduced with evident damage to the seminiferous tubules and interstitial tissues as shown by the histopathological picture of testis tissue sections. Accordingly, it can be deduced that fenugreek seeds powder exert a significant antifertility adverse effect on the female and male rats when supplemented at a considerable dose for an extended time interval

  9. The effect of hippophae rhamnoides extract on oral mucositis induced in rats with methotrexate.

    Science.gov (United States)

    Kuduban, Ozan; Mazlumoglu, Muhammed Recai; Kuduban, Selma Denktas; Erhan, Ertugrul; Cetin, Nihal; Kukula, Osman; Yarali, Oguzhan; Cimen, Ferda Keskin; Cankaya, Murat

    2016-01-01

    To investigate the effect of HRE (Hippophae rhamnoides extract) on oral mucositis induced in rats with MTX. Experimental animals were divided into groups as healthy (HG), HRE+MTX (HMTX), and control group, which received MTX (MTXC). HMTX group received 50 mg/kg HRE while MTXC and HG groups received equivolume distilled water with gavage once a day. After one hour of HRE and distilled water administration, HMTX and MTXC groups received a single dose of oral MTX 5 mg/ kg. This procedure was repeated for one month. The levels of MDA, IL-1β, and TNF-α were found to be significantly higher in the cheek, lower lip, and tongue tissue of the animals receiving MTX, compared with HG and HMTX groups; however, these parameters were lower in the cheek and low lip tissue, and a milder damage ocurred in these tissues, compared with the tongue tissue in MTXC group. No histopathologic damage was observed in the cheek, lower lip, and tongue tissues of the rats treated with HRE. This findings indicate that HRE as a natural product is an important advantage compared with synthetic drugs for prophylaxis of oral mucositis developed due to MTX.

  10. The effect of hippophae rhamnoides extract on oral mucositis induced in rats with methotrexate

    Directory of Open Access Journals (Sweden)

    Ozan Kuduban

    Full Text Available ABSTRACT Objective: To investigate the effect of HRE (Hippophae rhamnoides extract on oral mucositis induced in rats with MTX. Material and Methods: Experimental animals were divided into groups as healthy (HG, HRE+MTX (HMTX, and control group, which received MTX (MTXC. HMTX group received 50 mg/kg HRE while MTXC and HG groups received equivolume distilled water with gavage once a day. After one hour of HRE and distilled water administration, HMTX and MTXC groups received a single dose of oral MTX 5 mg/ kg. This procedure was repeated for one month. Results: The levels of MDA, IL-1β, and TNF-α were found to be significantly higher in the cheek, lower lip, and tongue tissue of the animals receiving MTX, compared with HG and HMTX groups; however, these parameters were lower in the cheek and low lip tissue, and a milder damage ocurred in these tissues, compared with the tongue tissue in MTXC group. No histopathologic damage was observed in the cheek, lower lip, and tongue tissues of the rats treated with HRE. Conclusion: This findings indicate that HRE as a natural product is an important advantage compared with synthetic drugs for prophylaxis of oral mucositis developed due to MTX.

  11. Oral toxicity evaluation of kefir-isolated Lactobacillus kefiranofaciens M1 in Sprague-Dawley rats.

    Science.gov (United States)

    Owaga, E E; Chen, M J; Chen, W Y; Chen, C W; Hsieh, R H

    2014-08-01

    Lactobacilli kefiranofaciens M1 has shown novel immunomodulation and anti-allergy probiotic attributes in cell and animal models. An acute oral toxicity assessment of L. kefiranofaciens M1 was evaluated in Sprague-Dawley rats. The rats were randomly assigned to four groups (12 rats/sex/group): the low dose group was orally gavaged with L. kefiranofaciens M1 at 3.0×10(8)cfu/kg bw while the medium dose and high dose groups received 9.0×10(9)cfu/kg bw and 1.8×10(10)cfu/kg bw, respectively, for 28days. The control group received phosphate buffer saline. The body weights were measured weekly while blood samples were collected for haematology and serum biochemistry tests. Histopathology of the organs (heart, liver, kidney, adrenal glands, spleen, ovary, testis), and urinalysis were conducted on study termination. The body weight gain of the L. kefiranofaciens M1 and control groups were comparable during the administration period. Overall, L. kefiranofaciens M1 did not induce adverse effects on haematology, serum biochemistry, and urinalysis parameters. Gross and microscopic histopathology of the organs revealed no toxicity effect of L. kefiranofaciens M1. In conclusion, 1.8×10(10)cfu/kg bw of L. kefiranofaciens M1 was considered as the no-observed-adverse-effect-level (NOAEL), which was the highest dose tested in the present study. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Tissue concentration-time profile of selenium after sodium selenite administration to rats

    Energy Technology Data Exchange (ETDEWEB)

    Kaneko, Megumi; Natsuhori, Masahiro; Ito, Nobuhiko [Department of Veterinary Radiology and Radiation Biology, Kitasato University School of Veterinary Medicine, Towada, Aomori (Japan); Sera, Koichiro [Cyclotron Research Center, Iwate Medical University, Takizuka, Iwate (Japan); Futatsugawa, Shoji [Nishina Memorial Cyclotron Center (NMCC), Takizuka, Iwate (Japan)

    1999-07-01

    Selenium (Se) concentration-time profiles in plasma and organs including liver, kidney, heart, lung, spleen and brain of rats (Jcl Wister, 9 wks old, n=32) were investigated after a single intravenous (iv) / oral (po) administration of sodium selenite (dose is equivalent to 2 mg/kg b.w. of Se). The Se concentration was determined by PIXE analysis. Among the investigated biological samples, Se concentration was the highest in the kidney or liver, followed by the heart, lung or spleen, then plasma, and the brain. Se concentrations in these organs were 0.5 to 5 times of plasma Se. The distribution profiles of Se in the organs were dependent on the route of administration. Furthermore, their profiles appeared almost parallel to the plasma Se-concentration in a logarithmic scale. Compared to the Se concentration-time profiles in plasma and organs by the route of administration, po group showed about 1/4-1/2 of the Se concentration in iv group except for kidney. Kidney kept relatively higher concentration of Se, which was similar in the both groups. This may explain our recently published data that urinary excretion was similar in the both groups. The relative oral bioavailability of plasma and each organ was calculated by the ratio of area under the concentration-time curve after oral administration (AUCpo) to AUCiv. Each organ appeared to have their own bioavailability (i.e., liver 39%, kidney 97%, heart 37%, lung 18%, spleen 10%, and brain 72%), where plasma was 46%. These results highly suggested that different Se distribution in organs by the different route of administration was due to the different metabolic profile. (author)

  13. Tissue concentration-time profile of selenium after sodium selenite administration to rats

    International Nuclear Information System (INIS)

    Kaneko, Megumi; Natsuhori, Masahiro; Ito, Nobuhiko; Sera, Koichiro; Futatsugawa, Shoji

    1999-01-01

    Selenium (Se) concentration-time profiles in plasma and organs including liver, kidney, heart, lung, spleen and brain of rats (Jcl Wister, 9 wks old, n=32) were investigated after a single intravenous (iv) / oral (po) administration of sodium selenite (dose is equivalent to 2 mg/kg b.w. of Se). The Se concentration was determined by PIXE analysis. Among the investigated biological samples, Se concentration was the highest in the kidney or liver, followed by the heart, lung or spleen, then plasma, and the brain. Se concentrations in these organs were 0.5 to 5 times of plasma Se. The distribution profiles of Se in the organs were dependent on the route of administration. Furthermore, their profiles appeared almost parallel to the plasma Se-concentration in a logarithmic scale. Compared to the Se concentration-time profiles in plasma and organs by the route of administration, po group showed about 1/4-1/2 of the Se concentration in iv group except for kidney. Kidney kept relatively higher concentration of Se, which was similar in the both groups. This may explain our recently published data that urinary excretion was similar in the both groups. The relative oral bioavailability of plasma and each organ was calculated by the ratio of area under the concentration-time curve after oral administration (AUCpo) to AUCiv. Each organ appeared to have their own bioavailability (i.e., liver 39%, kidney 97%, heart 37%, lung 18%, spleen 10%, and brain 72%), where plasma was 46%. These results highly suggested that different Se distribution in organs by the different route of administration was due to the different metabolic profile. (author)

  14. Development of an ultra-fast liquid chromatography-tandem mass spectrometry method for simultaneous determination of seven flavonoids in rat plasma: Application to a comparative pharmacokinetic investigation of Ginkgo biloba extract and single pure ginkgo flavonoids after oral administration.

    Science.gov (United States)

    Wang, Tianyang; Xiao, Jie; Hou, Huiping; Li, Pei; Yuan, Ziyue; Xu, Huarong; Liu, Ran; Li, Qing; Bi, Kaishun

    2017-08-15

    For deeper pharmacokinetic investigation and further curative application of ginkgo flavonoids, a delicate, efficient and precise UFLC-MS/MS technique for synchronous quantitation of seven flavonoids, apigenin, luteolin, naringenin, quercetin, diosmetin, kaempferol and isorhamnetin in rat plasma has been established. After mixing with the internal standard (IS) linarin, bio-samples were pretreated via ethyl acetate for liquid-liquid extraction, then isolated at 0.2ml/min flow rate on a Venusil MP C 18 chromatographic column (100mm×2.1mm, 3μm) by means of gradient elution. 0.1% formic acid-water and methanol system was used as the mobile phase. Mass spectrometric inspection was conducted on a 4000Q UFLC-MS/MS system with turbo ion spray source in patterns of negative ion and multiple reaction-monitoring (MRM). All calibration curves proved favorable linearity (R 2 ≥0.9918) in linear ranges. Intra-day and inter-day precisions didn't exceed 14.0% for all the analytes, and the accuracy was within 6.9%. Extraction recoveries of analytes and IS were less than ±15.0% of nominal concentrations. This method has been under thorough and firm verification for a comparative pharmacokinetic research after gavage between Ginkgo biloba extract and single pure ginkgo flavonoids. The results demonstrated that there're evident pharmacokinetic discrepancies, and possible structural influences were innovatively proposed. Generally, substitution with 3-hydroxylation, a double bond in ring C, ring B methoxylation often confer longer onset period. The existence of ring B catechol group gives rise to faster clearance. Copyright © 2017. Published by Elsevier B.V.

  15. Oral dosing by voluntary  administration of jellybeans. Refinement and reduction of variability

    DEFF Research Database (Denmark)

    Pakula, Malgorzata Maria; Dagnæs-Hansen, Frederik

    2016-01-01

    Administration of substances by oral gavage is a common procedure in biomedical research involving laboratory animals, however although highly efficient, the procedure includes fixation of the animals and is technically challenging. Oral gavage is a precise way to dose animals, however it may ind...

  16. Ginseng administration protects skeletal muscle from oxidative stress induced by acute exercise in rats.

    Science.gov (United States)

    Voces, J; Cabral de Oliveira, A C; Prieto, J G; Vila, L; Perez, A C; Duarte, I D G; Alvarez, A I

    2004-12-01

    Enzymatic activity was analyzed in the soleus, gastrocnemius (red and white) and plantaris muscles of acutely exercised rats after long-term administration of Panax ginseng extract in order to evaluate the protective role of ginseng against skeletal muscle oxidation. Ginseng extract (3, 10, 100, or 500 mg/kg) was administered orally for three months to male Wistar rats weighing 200 +/- 50 g before exercise and to non-exercised rats (N = 8/group). The results showed a membrane stabilizing capacity of the extract since mitochondrial function measured on the basis of citrate synthase and 3-hydroxyacyl-CoA dehydrogenase activities was reduced, on average, by 20% (P < 0.05) after exercise but the activities remained unchanged in animals treated with a ginseng dose of 100 mg/kg. Glutathione status did not show significant changes after exercise or treatment. Lipid peroxidation, measured on the basis of malondialdehyde levels, was significantly higher in all muscles after exercise, and again was reduced by about 74% (P < 0.05) by the use of ginseng extract. The administration of ginseng extract was able to protect muscle from exercise-induced oxidative stress irrespective of fiber type.

  17. Ginseng administration protects skeletal muscle from oxidative stress induced by acute exercise in rats

    Directory of Open Access Journals (Sweden)

    J. Voces

    2004-12-01

    Full Text Available Enzymatic activity was analyzed in the soleus, gastrocnemius (red and white and plantaris muscles of acutely exercised rats after long-term administration of Panax ginseng extract in order to evaluate the protective role of ginseng against skeletal muscle oxidation. Ginseng extract (3, 10, 100, or 500 mg/kg was administered orally for three months to male Wistar rats weighing 200 ± 50 g before exercise and to non-exercised rats (N = 8/group. The results showed a membrane stabilizing capacity of the extract since mitochondrial function measured on the basis of citrate synthase and 3-hydroxyacyl-CoA dehydrogenase activities was reduced, on average, by 20% (P < 0.05 after exercise but the activities remained unchanged in animals treated with a ginseng dose of 100 mg/kg. Glutathione status did not show significant changes after exercise or treatment. Lipid peroxidation, measured on the basis of malondialdehyde levels, was significantly higher in all muscles after exercise, and again was reduced by about 74% (P < 0.05 by the use of ginseng extract. The administration of ginseng extract was able to protect muscle from exercise-induced oxidative stress irrespective of fiber type.

  18. An oral sensitization model in Brown Norway rats to screen for potential allergenicity of food proteins

    NARCIS (Netherlands)

    Knippels, L.M.J.; Houben, G.F.; Spanhaak, S.; Penninks, A.H.

    1999-01-01

    We developed an oral sensitization protocol for food proteins for the rat. Young Brown Norway (BN) rats were exposed to 1 mg ovalbumin (OVA) by daily gavage dosing for 42 days without the use of an adjuvant. OVA-specific IgE and IgG responses were determined by ELISA. On an oral challenge with OVA

  19. Oral warfarin intake affects skin inflammatory cytokine responses in rats.

    Science.gov (United States)

    Aleksandrov, Aleksandra Popov; Mirkov, Ivana; Zolotarevski, Lidija; Ninkov, Marina; Mileusnic, Dina; Kataranovski, Dragan; Kataranovski, Milena

    2017-09-01

    Warfarin is an anticoagulant used in prevention/prophylaxis of thromboembolism. Besides the effects on coagulation, non-hemorrhagic reactions have also been documented. Although cutaneous reactions were reported in some patients, the impact on skin immunity was not explored. In the present paper, the effect of 30-day oral warfarin intake on skin cytokine responses in rats was analyzed. Increased release of inflammatory cytokines (TNF, IL-1β and IL-10) was noted by skin explants from rats which received warfarin, but without effect on IL-6. No impact on epidermal cell cytokine secretion was seen, except a tendency of an increase of IL-6 response to stimulation with microbial product lipopolysaccharide (LPS). Topical application of contact allergen dinitrochlorobenzene (DNCB) resulted in slight (numerical solely) increase of TNF release by skin explants of warfarin-treated animals, while epidermal cells responded by increased secretion of all four cytokines examined. The data presented provide new information on the potential of oral warfarin to modulate skin innate immune activity. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Effect of Oral Administration of Pheretima Aspergillum (Earthworm ...

    African Journals Online (AJOL)

    The PA-treated MCAo rats showed greatly decreased neuronal death, glial proliferation, and S100B proteins in the penumbra area of the cortex and in the ischemic core area of the cortex, but BDNF did not changed. These results demonstrated novel and detailed cellular mechanisms underlying the neuroprotective effects ...

  1. Histological Studies Of The Effects Of Oral Administration Of ...

    African Journals Online (AJOL)

    on the neurons of the intracranial visual relay centre and this may probably have some adverse effects on visual sensibilities by its deleterious effects on the cells of the lateral geniculate body (LGB) of adult Wistar rats. It is therefore ... Key words: Artesunate, lateral geniculate body (LGB), decreased cellular population,

  2. Effects of Iron Administration on the Diameter of Cells of Growth Cartilage of Rat Pups During Pregnancy.

    Science.gov (United States)

    Umbreen, Faiza; Qamar, Khadija; Shaukat, Sadia; Tasawar, Amna

    2017-07-01

    To determine the effect of oral iron administration on pregnant rats on the diameter of cells of growth plate of rat pups. Experimental study. Anatomy Department, Army Medical College, Rawalpindi in collaboration with National Institute of Health (NIH), Islamabad from March to November 2016. Group Acontaining 8 pregnant rats was control group, and group B containing same number of pregnant rats was the study group. Control group Awas on standard diet throughout pregnancy. Iron was given to the experimental group B for 21 days (throughout pregnancy) in the form of syrup 0.5ml daily (2.75 mg of elemental iron) given in water. Rat infants were born via spontaneous vaginal delivery. Inclusion criteria for infants was pups born at term which were active and taking feed. Femur from each rat infant of right side was removed for the growth plate investigation. Processing, embedding and staining with Hematoxylin and Eosin, Perl's stain for histological study was done. The cell diameter in hypertrophy and proliferative zone was evaluated. Mean values of the diameter of chondrocytes in both the zones of growth cartilage of femur were measured. Diameter of the cells in hypertrophy and proliferative zones was considerably decreased in group B as compared to group A. Administration of iron during pregnancy with normal iron status can disturb growth of the rat infant through its accumulation in the epiphyseal plate of femur. The cell diameter of the hypertrophy and proliferative zones was markedly reduced in iron administered group as compared to the control group.

  3. Evaluation of pancreatic lipase activity by simple urine analysis after oral administration of a new iodine-131-labeled triglyceride

    International Nuclear Information System (INIS)

    Kropp, J.; Knapp, F.F. Jr.; Weyenberg, A.; McPherson, D.W.; Ambrose, K.R.; Callahan, A.P.; Bergmann, K. von; Biersack, H.J.

    1994-01-01

    A new iodine-131-labeled triglyceride analogue called ''MIPAG'' [1,2-dipalmitoyl-3-[(15-p-iodophenyl) pentadecan-1-oyl]rac-glycerol] has been prepared in which 15-(p-iodophenyl)pentadecanoic acid (IPPA) is attached to position-3. MIPAG has been developed for the evaluation of pancreatic exocrine function by simple urine analysis and has been evaluated in rats and humans. After oral administration, IPPA is released from the triglyceride by the action of pancreatic lipases followed by intestinal absorption and the principal IPPA metabolite (p-iodobenzoic acid. IBA) is primarily excreted in the urine. Excretion in the urine and feces was evaluated in rats, as well as the biodistribution in various organs over 21 days. Twenty patients without pancreatic disease (normals) and four patients with pancreatic insufficiency were also investigated. Following oral administration of 30 μCi of MIPAG, urine was collected for two successive 24-h periods. Blood samples were drawn and thin-layer chromatographic (TLC) analysis was performed on the serum lipid extracts. Urine from normals contained 44.9%±7.7% and 61.8%±8.4% of the administered activity after 24 and 48 h, respectively. The patients with pancreatic insufficiency excreted 13.1%±5.6% and 18.9%±6.2%, respectively, which was significantly decreased (P<0.001) compared with normals. The TLC profiles showed an increasing proportion of IBA with time. Urine analysis after oral administration of MIPAG thus appears to be an attractive new technique for the evaluation of pancreatic lipase activity by a simple urine analysis. (orig.)

  4. The effect of cola consumption on oral mucosa in rats.

    Science.gov (United States)

    Kapicloğlu, S; Baki, A H; Tekelioğlu, Y; Araz, K

    2000-01-01

    Drinks that contain phosphoric acid have been shown to have erosive effects and cola drinks are strongly acidic (pH 2.5). Gingivitis may be caused by dietary acids. Therefore, this study analyses the interaction of Coca Cola consumption and oral mucosal damage. Thirty rats were divided into three groups of 10. The animals received saline (pH 7.0) or HCl acid buffered to pH 2.6 or Coca Cola (pH 2.6) per os with 24-h free access to these solutions. A biopsy was taken from the front of the gingiva and the tongue. Histopathological analysis showed no specific lesion and there were no differences among saline, Coca Cola and HCl groups. Flow cytometric analysis was used to assess proliferative activity. In the HCl acid and Coca Cola groups, cell cycle analysis showed that the effects of Coca Cola and HCl acid in inducing oral mucosal damage are similar. In both Coca Cola [G0/G1, 70.38+/-7.9; S, 28.06+/-10.13; G2/M, 1.62+/-2.80; proliferative index (PI), 28.68+/-7.981 and HCI (G0/G1, 67.7+/-18.9; S, 27.8+/-17.5; G2/M, 4.4+/-3.8; PI, 30.9+/-20.98), the rat cell population G0/G1 and G2/M phases were found to be low (p Coca Cola and HCl acid have similar proliferative and regenerative effects on oral mucosa, and it is possible that their regenerative effects are caused as a result of an irritant effect.

  5. Serum concentrations of buprenorphine after oral and parenteral administration in male mice

    DEFF Research Database (Denmark)

    Kalliokoski, Otto; Jacobsen, Kirsten R; Hau, Jann

    2011-01-01

    Buprenorphine is the most commonly used drug for peri-operative pain relief in laboratory rodents. The systemic concentrations of buprenorphine were measured in mice following administration intravenously (IV), subcutaneously (SC), orally by gavage and by voluntary ingestion, to determine the post-administration...... serum concentration of buprenorphine. Voluntarily ingested buprenorphine resulted in long-lasting high serum concentrations, as did oral gavage administration (24h serum concentration: 110ngh/mL for both routes of administration). In contrast, buprenorphine administered parenterally remained...... in the circulation for a substantially shorter time (24h serum concentration for IV and SC were 40ngh/mL and 30ngh/mL, respectively). This marked difference was probably due to the higher dose used for oral administration, which is regarded necessary for sufficient analgesic effect, and to the slower absorption...

  6. Serum metabolic changes in rats after intragastric administration of dextromethorphan.

    Science.gov (United States)

    Bao, Shihui; Zhang, Jing; Lin, Zixia; Su, Ke; Mo, Jingjing; Hong, Lin; Qian, Shuyi; Chen, Lianguo; Sun, Fa; Wen, Congcong; Wu, Qing; Hu, Lufeng; Lin, Guanyang; Wang, Xianqin

    2017-03-01

    Dextromethorphan is recognized as a substance of abuse around the world. An estimated 3.1 million people between the ages of 12 and 25 years (5.3%) misused over-the-counter cough and cold medications in 2006. In this study, we developed a serum metabolomic method by gas chromatography-mass spectrometry (GC-MS) to evaluate the effect of abuse of dextromethorphan on rats. The dextromethorphan-treated rats were given 12, 24 and 48 mg/kg (low, medium, high) of dextromethorphan by intragastric administration each day for 3 days. Partial least squares-discriminate analysis revealed that intragastric administration of dextromethorphan induced metabolic perturbations. Compared with the control (healthy) group, the levels of propanoic acid, urea, heptafluorobutanoic acid, 2-hexyldecanoic acid and butanedioic acid of the low group decreased; levels of propanoic acid and heptafluorobutanoic acid of the medium group decreased, while that of benzoic acid increased; and levels of 2-hexyldecanoic acid, glycerol and butanedioic acid of the high group increased. These biomarkers are involved in the citric acid cycle, urea cycle, glycerolipid metabolism and tricarboxylic acid cycle. The results indicate that the metabolomic method by GC-MS may be useful to elucidate abuse of dextromethorphan. According to the pathological changes in the liver at different dosages, dextromethorphan is not hepatotoxic after intragastric administration of 12, 24 and 48 mg/kg for 3 days. Copyright © 2016 John Wiley & Sons, Ltd.

  7. Oral absorption and oxidative metabolism of atrazine in rats evaluated by physiological modeling approaches

    International Nuclear Information System (INIS)

    McMullin, Tami S.; Hanneman, William H.; Cranmer, Brian K.; Tessari, John D.; Andersen, Melvin E.

    2007-01-01

    Atrazine (ATRA) is metabolized by cytochrome P450s to the chlorinated metabolites, 2-chloro-4-ethylamino-6-amino-1,3,5-triazine (ETHYL), 2-chloro-4-amino-6-isopropylamino-1, 3, 5-triazine (ISO), and diaminochlorotriazine (DACT). Here, we develop a set of physiologically based pharmacokinetic (PBPK) models that describe the influence of oral absorption and oxidative metabolism on the blood time course curves of individual chlorotriazines (Cl-TRIs) in rat after oral dosing of ATRA. These models first incorporated in vitro metabolic parameters to describe time course plasma concentrations of DACT, ETHYL, and ISO after dosing with each compound. Parameters from each individual model were linked together into a final composite model in order to describe the time course of all 4 Cl-TRIs after ATRA dosing. Oral administration of ISO, ETHYL and ATRA produced double peaks of the compounds in plasma time courses that were described by multiple absorption phases from gut. An adequate description of the uptake and bioavailability of absorbed ATRA also required inclusion of additional oxidative metabolic clearance of ATRA to the mono-dealkylated metabolites occurring in GI a tract compartment. These complex processes regulating tissue dosimetry of atrazine and its chlorinated metabolites likely reflect limited compound solubility in the gut from dosing with an emulsion, and sequential absorption and metabolism along the GI tract at these high oral doses

  8. Tissue distribution and excretion kinetics of orally administered silica nanoparticles in rats

    Directory of Open Access Journals (Sweden)

    Lee JA

    2014-12-01

    Full Text Available Jeong-A Lee,1 Mi-Kyung Kim,1 Hee-Jeong Paek,1 Yu-Ri Kim,2 Meyoung-Kon Kim,2 Jong-Kwon Lee,3 Jayoung Jeong,3 Soo-Jin Choi1 1Department of Food Science and Technology, Seoul Women’s University, Seoul, Republic of Korea; 2Department of Biochemistry and Molecular Biology, Korea University Medical School and College, Seoul, Republic of Korea; 3Toxicological Research Division, National Institute of Food and Drug Safety Evaluation, Chungchungbuk–do, Republic of Korea Purpose: The effects of particle size on the tissue distribution and excretion kinetics of silica nanoparticles and their biological fates were investigated following a single oral administration to male and female rats. Methods: Silica nanoparticles of two different sizes (20 nm and 100 nm were orally administered to male and female rats, respectively. Tissue distribution kinetics, excretion profiles, and fates in tissues were analyzed using elemental analysis and transmission electron microscopy. Results: The differently sized silica nanoparticles mainly distributed to kidneys and liver for 3 days post-administration and, to some extent, to lungs and spleen for 2 days post-administration, regardless of particle size or sex. Transmission electron microscopy and energy dispersive spectroscopy studies in tissues demonstrated almost intact particles in liver, but partially decomposed particles with an irregular morphology were found in kidneys, especially in rats that had been administered 20 nm nanoparticles. Size-dependent excretion kinetics were apparent and the smaller 20 nm particles were found to be more rapidly eliminated than the larger 100 nm particles. Elimination profiles showed 7%–8% of silica nanoparticles were excreted via urine, but most nanoparticles were excreted via feces, regardless of particle size or sex. Conclusion: The kidneys, liver, lungs, and spleen were found to be the target organs of orally-administered silica nanoparticles in rats, and this organ

  9. Effect of exercise on turnover and fate of 4-14C$-cholesterol administered intraperitoneally and orally to rats

    International Nuclear Information System (INIS)

    Fukuda, Nobuhiro; Tsuge, Yasuyuki; Sugano, Michihiro

    1979-01-01

    The fate of [4- 14 C]-cholesterol administered intraperitoneally or orally was compared in exercised (treadmill running for 14 days) and sedentary rats. Plasma triglyceride, phospholipid and cholesterol decreased in exercised rats and this reduction lasted at least for 10 days after exercise was terminated. When rats received [4- 14 C]-cholesterol intraperitoneally or orally, the turnover rate of serum cholesterol was considerably higher in exercised rats at the time shortly after the administration of the label. The radioactivity remaining in the liver was consistently lower in exercised rats, whereas that in extrahepatic tissues was the same between two groups. Excretion into feces of the label as total steroids was moderately enhanced by exercise. This effect was almost entirely ascribed to the increase in output of the label shortly after the administration. These results suggest that the mechanism responsible for cholesterol lowering effect of exercise is mainly attributable to the increase in turnover of cholesterol in the hepato-plasmic system. The moderate increase in fecal output of endogenous steroids may be the reflection of the increased turnover. (author)

  10. Sub-chronic oral toxicity of Cuminum cyminum L.'s essential oil in female Wistar rats.

    Science.gov (United States)

    Taghizadeh, Mohsen; Ostad, Seyed Naser; Asemi, Zatollah; Mahboubi, Mohaddese; Hejazi, Sara; Sharafati-Chaleshtori, Reza; Rashidi, Aliakbar; Akbari, Hosein; Sharifi, Nasrin

    2017-08-01

    The current study was performed to evaluate the toxicity of Cuminum cyminum L. (C. cyminum)'s essential oil after 23 days and 45 days of repeated oral administration in female Wistar rats. A total of 80 healthy female Wistar rats were randomly selected and divided into 4 groups. The rats were gavaged with C. cyminum's essential oil at dose levels of 0, 250, 500 and 1000 mg/kg/day. Clinical signs, body weight, hematology, serum biochemistry and organ histopathology were assessed once after 23 days and again after 45 days passed from the start of the intervention. Oral administration of C. cyminum's essential oil had no observed adverse effects on clinical signs, mortality, body weight, hematology, biochemistry and organ histology (liver, kidneys, spleen and lungs) in a sample of healthy female Wistar rats after 23 days and 45 days from the start of the study. However, an increase in serum levels of alanine transaminase (ALT) was found only at dose level of 1000 mg/kg/d C. cyminum's essential oil, after the 23-days interval. We conservatively defined the non-observed adverse effect level (NOAEL) for C. cyminum's essential oil as 500 mg/kg/d in female Wistar rats. The present study results should be treated with cautious in terms of the other organs' toxicity. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Increased oral AUC of baicalin in streptozotocin-induced diabetic rats due to the increased activity of intestinal beta-glucuronidase.

    Science.gov (United States)

    Liu, Li; Deng, Yuan-Xiong; Liang, Yan; Pang, Xiao-Yan; Liu, Xiao-Dong; Liu, Yao-Wu; Yang, Jian-Song; Xie, Lin; Wang, Guang-Ji

    2010-01-01

    The purpose of the study was to investigate the pharmacokinetics of baicalin, a major bioactive component of Scutellariae radix, in diabetic conditions. The 4-week diabetic rats were induced by intraperitoneal administration of streptozotocin. Plasma concentrations of baicalin were measured following oral (200 mg/kg) or intravenous (12 mg/kg) administration. Everted intestinal transport, intestinal mucosal metabolism of baicalin and intestinal beta-glucuronidase activity were also investigated. It was found that the diabetic condition significantly increased the exposure of baicalin following oral doses (AUC 100.77 +/- 4.16 microg x h/mL in diabetic rats vs. 48.48 +/- 7.94 microg x h/mL in normal rats). In contrast, the diabetic condition significantly decreased the exposure of baicalin following intravenous doses (AUC 11.20 +/- 2.28 microg x h/mL in diabetic rats vs. 18.02 +/- 3.45 microg x h/mL in normal rats). We also found lower apparent permeability coefficients of baicalin in the ileum of diabetic rats (8.43 x 10 (-6) +/- 2.40 x 10 (-6) cm/s in diabetic rats vs. 5.21 x 10 (-5) +/- 1.55 x 10 (-5) cm/s in normal rats). Further studies showed that the diabetic condition enhanced the hydrolysis of baicalin to baicalein in intestinal mucosal, accompanied by an increase of beta-glucuronidase activity. All these results suggested that the higher oral exposure of baicalin in diabetic rats did not result from the decreased hepatic metabolism or increased intestinal absorption of baicalin. The enhancement of intestinal beta-glucuronidase activity may partly account for the higher exposure of baicalin in diabetic rats after oral administration. Copyright Georg Thieme Verlag KG Stuttgart . New York.

  12. Lactobacillus salivarius REN inhibits rat oral cancer induced by 4-nitroquioline 1-oxide.

    Science.gov (United States)

    Zhang, Ming; Wang, Fang; Jiang, Lu; Liu, Ruihai; Zhang, Lian; Lei, Xingen; Li, Jiyou; Jiang, Jingli; Guo, Huiyuan; Fang, Bing; Zhao, Liang; Ren, Fazheng

    2013-07-01

    Despite significant advances in cancer therapy, cancer-related mobility and mortality are still rising. Alternative strategies such as cancer prevention thus become essential. Probiotics represent an emerging option for cancer prevention, but studies are limited to colon cancers. The efficiency of probiotics in the prevention of other cancers and the correlative mechanism remains to be explored. A novel probiotics Lactobacillus salivarius REN (L. salivarius REN) was isolated from centenarians at Bama of China, which showed highly potent antigenotoxicity in an initial assay. 4-nitroquioline 1-oxide (4NQO)-induced oral cancer model was introduced to study the anticancer activity of L. salivarius REN in vivo. The results indicated that oral administration of probiotic L. salivarius REN or its secretions could effectively suppress 4NQO-induced oral carcinogenesis in the initial and postinitial stage, and the inhibition was in a dose-dependent manner. A significant decrease of neoplasm incidence (65%-0%) was detected in rats fed with the high dose of L. salivarius REN [5 × 10(10) CFU/kg body weight (bw)/d]. In vivo evidences indicated that the probiotics inhibited 4NQO-induced oral cancer by protecting DNA against oxidative damage and downregulating COX-2 expression. L. salivarius REN treatment significantly decreased the expression of proliferating cell nuclear antigen (PCNA) and induced apoptosis in a dose-dependent manner. Our findings suggest that probiotics may act as potential agents for oral cancer prevention. This is the first report showing the inhibitory effect of the probiotics on oral carcinogenesis. ©2013 AACR.

  13. Comparison of radioisotopic studied calcium metabolism in the orally administered and inhaled cadmium rat

    International Nuclear Information System (INIS)

    Fauran-Clavel, M.J.; Oustrin, J.; Godin, J.; Boudene, C.

    1982-01-01

    The radioisotopic study of calcium metabolism in the rat after oral administration of cadmium, 8 mg/kg during 13 weeks, has shown two different effects of this ion: 1) in the intestine, cadmium inhibits the absorption of calcium by active transport; 2) in the deep bone compartment, the decrease of the bone calcium used for the crystallization and slowly exchangeable with the calcium central pool (serum, extracellular and soft tissues calcium) is combined with a reduction of the exchange rates between the two compartments. When administered through a microparticle aerosol inhalation (1 mg/m 3 of air, 30 mn a day, during 12 weeks), cadmium's main target organ is the deep bone compartment. For both modes of administration, the slowing down of osteogenesis is confirmed by a drop in serum alkaline phosphatase after a four weeks period which reflects a decrease of the osteoblastic activity. Therefore it appears that the effects on bones observed during the chronic oral cadmium administration, do not result from a malabsorption of intestine calcium but also from the very action the Cd ++ ion on the bone crystallization process [fr

  14. In vivo analysis of supersaturation/precipitation/absorption behavior after oral administration of pioglitazone hydrochloride salt; determinant site of oral absorption.

    Science.gov (United States)

    Tanaka, Yusuke; Sugihara, Masahisa; Kawakami, Ayaka; Imai, So; Itou, Takafumi; Murase, Hirokazu; Saiki, Kazunori; Kasaoka, Satoshi; Yoshikawa, Hiroshi

    2017-08-30

    The purpose of this study was to evaluate in vivo supersaturation/precipitation/absorption behavior in the gastrointestinal (GI) tract based on the luminal concentration-time profiles after oral administration of pioglitazone (PG, a highly permeable lipophilic base) and its hydrochloride salt (PG-HCl) to rats. In the in vitro precipitation experiment in the classic closed system, while the supersaturation was stable in the simulated gastric condition, PG drastically precipitated in the simulated intestinal condition, particularly at a higher initial degree of supersaturation. Nonetheless, a drastic and moderate improvement in absorption was observed in vivo at a low and high dose of PG-HCl, respectively. Analysis based on the luminal concentration of PG after oral administration of PG-HCl at a low dose revealed that most of the dissolved PG emptied from the stomach was rapidly absorbed before its precipitation in the duodenum. At a high dose of PG-HCl, PG partly precipitated in the duodenum but was absorbed to some extent. Therefore, the extent of the absorption was mainly dependent on the duodenal precipitation behavior. Furthermore, a higher-than expected absorption after oral administration of PG-HCl from in vitro precipitation study may be due to the absorption process in the small intestine, which suppresses the precipitation by removal of the drug. This study successfully clarify the impact of the absorption process on the supersaturation/precipitation/absorption behavior and key absorption site for a salt formulation of a highly permeable lipophilic base based on the direct observation of in vivo luminal concentration. Our findings may be beneficial in developing an ideal physiologically based pharmacokinetic model and in vitro predictive dissolution tools and/or translating the in silico and in vitro data to the in vivo outcome. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Diazinon and Cadmium Neurotoxicity in Rats after an Experimental Administration

    Directory of Open Access Journals (Sweden)

    Róbert Toman

    2012-10-01

    Full Text Available The aim of this study was to describe the changes in cholinesterase activity in separate doses and after coadministration of cadmium and diazinon intraperitoneally and to assess toxicity and interactions of diazinon and cadmium on the nervous system in male rats. 40 male rats were randomly divided into three experimental and one control group (10 rats in each group. Blood analyzes were performed 36 hours after an intraperitoneal administration of observed compounds. The statistical evaluation of the results showed significantly (P < 0.01 reduced activity of cholinesterase in all experimental groups. The enzyme activity decreased from the control value 3.69 μkat/L to 1.81 μkat/L (diazinon group, 1.83 μkat/L (cadmium group and 1.35 μkat/L (cadmium+diazinon group. These results indicate that both cadmium and diazinon are potent to manifest the neurotoxic effects. Moreover, a synergistic effect of the co-administered cadmium and diazinon in the nervous system has been observed.

  16. Neurochemical Effects of Chronic Administration of Calcitriol in Rats

    Directory of Open Access Journals (Sweden)

    Pei Jiang

    2014-12-01

    Full Text Available Despite accumulating data showing the various neurological actions of vitamin D (VD, its effects on brain neurochemistry are still far from fully understood. To further investigate the neurochemical influence of VD, we assessed neurotransmitter systems in the brain of rats following 6-week calcitriol (1,25-dihydroxyvitamin D administration (50 ng/kg/day or 100 ng/kg/day. Both the two doses of calcitriol enhanced VDR protein level without affecting serum calcium and phosphate status. Rats treated with calcitriol, especially with the higher dose, exhibited elevated γ-aminobutyric acid (GABA status. Correspondingly, the mRNA expression of glutamate decarboxylase (GAD 67 was increased. 100 ng/kg of calcitriol administration also increased glutamate and glutamine levels in the prefrontal cortex, but did not alter glutamine synthetase (GS expression. Additionally, calcitriol treatment promoted tyrosine hydroxylase (TH and tryptophan hydroxylase 2 (TPH2 expression without changing dopamine and serotonin status. However, the concentrations of the metabolites of dopamine and serotonin were increased and the drug use also resulted in a significant rise of monoamine oxidase A (MAOA expression, which might be responsible to maintain the homeostasis of dopaminergic and serotonergic neurotransmission. Collectively, the present study firstly showed the effects of calcitriol in the major neurotransmitter systems, providing new evidence for the role of VD in brain function.

  17. Prevention of urogenital infections by oral administration of probiotic lactobacilli

    Directory of Open Access Journals (Sweden)

    Vedran Slačanac

    2010-09-01

    Full Text Available In general, lactobacilli are nonpathogenic part of the normal urogenital microflora and have been recognized as a barrier against colonization of unwanted (pathogen microflora. The results of many in vitro studies suggest following mechanisms of probiotic lactobacilli action in urogenital tract: adhesion to urogenital cells, competition with pathogens for adhesive sites, production of biosurfactants, co-aggregation with pathogens, production of antimicrobial substances (organic acids, hydrogen peroxide and bacteriocins and stimulation of immune system. From 80 different lactobacilli species isolated from human or animal intestinal and urogenital tract, only few lactobacilli strains possess optimal properties to be effective as probiotic therapeutics against infections in the urogenital tract. Combination of Lactobacillus rhamnosus GR-1 and Lactobacillus fermentum RC-14 was proposed as the best one for epithelial vaginal cells colonization and inhibition of uropathogens adhesion. The results of a number of clinical studies confirmed beneficial role of oral lactobacilli. However, the most of commercially available Lactobacillus strains, which are ordinary used in fermented dairy products,are seriously limited in protection of urogenital tract when they are ingested orally.

  18. Effects of oral administration of Phyllanthus amarus leaf extract on ...

    African Journals Online (AJOL)

    The histological findings indicated that the treated sections of the kidneys showed hypertrophy of blood vessels, mild-severe infiltrate of chronic inflammatory cells and varying degrees of tubular necrosis when compared to the control sections. The findings indicated that the administration of Phyllanthus amarus extract has ...

  19. Effects of Long-Term Ayahuasca Administration on Memory and Anxiety in Rats.

    Science.gov (United States)

    Favaro, Vanessa Manchim; Yonamine, Maurício; Soares, Juliana Carlota Kramer; Oliveira, Maria Gabriela Menezes

    2015-01-01

    Ayahuasca is a hallucinogenic beverage that combines the action of the 5-HT2A/2C agonist N,N-dimethyltryptamine (DMT) from Psychotria viridis with the monoamine oxidase inhibitors (MAOIs) induced by beta-carbonyls from Banisteriopsis caapi. Previous investigations have highlighted the involvement of ayahuasca with the activation of brain regions known to be involved with episodic memory, contextual associations and emotional processing after ayahuasca ingestion. Moreover long term users show better performance in neuropsychological tests when tested in off-drug condition. This study evaluated the effects of long-term administration of ayahuasca on Morris water maze (MWM), fear conditioning and elevated plus maze (EPM) performance in rats. Behavior tests started 48h after the end of treatment. Freeze-dried ayahuasca doses of 120, 240 and 480 mg/kg were used, with water as the control. Long-term administration consisted of a daily oral dose for 30 days by gavage. The behavioral data indicated that long-term ayahuasca administration did not affect the performance of animals in MWM and EPM tasks. However the dose of 120 mg/kg increased the contextual conditioned fear response for both background and foreground fear conditioning. The tone conditioned response was not affected after long-term administration. In addition, the increase in the contextual fear response was maintained during the repeated sessions several weeks after training. Taken together, these data showed that long-term ayahuasca administration in rats can interfere with the contextual association of emotional events, which is in agreement with the fact that the beverage activates brain areas related to these processes.

  20. Effects of Long-Term Ayahuasca Administration on Memory and Anxiety in Rats.

    Directory of Open Access Journals (Sweden)

    Vanessa Manchim Favaro

    Full Text Available Ayahuasca is a hallucinogenic beverage that combines the action of the 5-HT2A/2C agonist N,N-dimethyltryptamine (DMT from Psychotria viridis with the monoamine oxidase inhibitors (MAOIs induced by beta-carbonyls from Banisteriopsis caapi. Previous investigations have highlighted the involvement of ayahuasca with the activation of brain regions known to be involved with episodic memory, contextual associations and emotional processing after ayahuasca ingestion. Moreover long term users show better performance in neuropsychological tests when tested in off-drug condition. This study evaluated the effects of long-term administration of ayahuasca on Morris water maze (MWM, fear conditioning and elevated plus maze (EPM performance in rats. Behavior tests started 48h after the end of treatment. Freeze-dried ayahuasca doses of 120, 240 and 480 mg/kg were used, with water as the control. Long-term administration consisted of a daily oral dose for 30 days by gavage. The behavioral data indicated that long-term ayahuasca administration did not affect the performance of animals in MWM and EPM tasks. However the dose of 120 mg/kg increased the contextual conditioned fear response for both background and foreground fear conditioning. The tone conditioned response was not affected after long-term administration. In addition, the increase in the contextual fear response was maintained during the repeated sessions several weeks after training. Taken together, these data showed that long-term ayahuasca administration in rats can interfere with the contextual association of emotional events, which is in agreement with the fact that the beverage activates brain areas related to these processes.

  1. Prevention of salt induced hypertension in rats by oral administration ...

    African Journals Online (AJOL)

    A high salt diet can elevate blood pressure in humans and other susceptible animal species. A high proportion of our indigenous foods are fermented products and. Lactobacillus species have been reported to be the predominant flora in many of our indigenous fermentation processes. In this study, the effect of concurrent ...

  2. Effect of oral administration of Terminalia chebula on gastric emptying: an experimental study.

    Directory of Open Access Journals (Sweden)

    Tamhane M

    1997-01-01

    Full Text Available Terminalia chebula is a commonly advocated agent in Ayurveda for improving gastrointestinal motility. Charles Foster rats (150-200 gms of either sex were divided into four groups as follows--Group 1 (n = 15 normal animals; Group II (n = 6 rats administered metoclopramide (1.35 mg/kg; Group III (n = 8 rats given atropine (0.45 mg/kg. These agents were injected intramuscularly, 30 mins before the experiment. Rats from Group IV (n = 8 were administered Terminalia chebula (100 mg/kg/day for 15 days orally. Metoclopramide and atropine have established prokinetic and antikinetic activities respectively and are therefore included for comparison. All rats were then given a test meal of methyl cellulose (1.5% mixed with phenol red (50 mg/100 ml orally and gastric emptying was measured 20 mins later. Gastric emptying of normal rats (Group I was found to be 51.6 +/- 7.79%. Metoclopramide significantly increased the gastric emptying (76.33 +/- 12.37%; p < 0.01 and atropine inhibited the motility (% gastric emptying being 7.26 +/- 19.76%; p < 0.01. Terminalia chebula was found to increase the percent gastric emptying (86.57 +/- 6.65%; p < 0.01. Thus from this study it appears that Terminalia chebula can serve as an useful alternative to prokinetic drugs available today.

  3. Effects of oral administration of titanium dioxide fine-sized particles on plasma glucose in mice.

    Science.gov (United States)

    Gu, Ning; Hu, Hailong; Guo, Qian; Jin, Sanli; Wang, Changlin; Oh, Yuri; Feng, Yujie; Wu, Qiong

    2015-12-01

    Titanium dioxide (TiO2) is an authorized additive used as a food colorant, is composed of nano-sized particles (NP) and fine-sized particles (FP). Previous study reported that oral administration of TiO2 NPs triggers an increase in plasma glucose of mice. However, no previous studies have focused on toxic effects of TiO2 FPs on plasma glucose homeostasis following oral administration. In the current study, mice were orally administered TiO2 FPs greater than 100 nm in size (64 mg/kg body weight per day), and effects on plasma glucose levels examined. Our results showed that titanium levels was not changed in mouse blood, livers and pancreases after mice were orally administered TiO2 FPs. Biochemical analyzes showed that plasma glucose and ROS levels were not affected by TiO2 FPs. Histopathological results showed that TiO2 FPs did not induce pathology changes in organs, especially plasma glucose homeostasis regulation organs, such as pancreas and liver. Western blotting showed that oral administration of TiO2 FPs did not induce insulin resistance (IR) in mouse liver. These results showed that, TiO2 FPs cannot be absorbed via oral administration and affect plasma glucose levels in mice. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Eliminating the need for fasting with oral administration of bisphosphonates

    DEFF Research Database (Denmark)

    Pazianas, Michael; Abrahamsen, Bo; Ferrari, Serge

    2013-01-01

    or beverages create complexes that cannot be absorbed. For this reason, they must be taken on an empty stomach, and a period of up to 2 hours must elapse before the consumption of any food or drink other than plain water. This routine is not only inconvenient but can lead to discontinuation of treatment......Bisphosphonates are the major treatment of choice for osteoporosis, given that they are attached preferentially by bone and significantly reduce the risk of fractures. Oral bisphosphonates are poorly absorbed (usually less than 1% for nitrogen-containing bisphosphonates) and when taken with food......, and when mistakenly taken with food, may result in misdiagnosis of resistance to or failure of treatment. The development of an enteric-coated delayed-release formulation of risedronate with the addition of the calcium chelator, ethylenediaminetetraacetic acid (EDTA), a widely used food stabilizer...

  5. The increase elimination rate of tritium after administration of furosemide in rats

    International Nuclear Information System (INIS)

    Chirovici, Maria; Jiquidi, Luminita; Reviu, Eugen

    2001-01-01

    It is well known that tritium has certain characteristics that present serious problems for dosimetry and health risk assessment. National Council on Radiation Protection recommends for persons contaminated with tritium oral intake of fluid (e.g. water, fruit juice, tea, coffee or beer), or instillation with 5 % glucose under a doctor's care, together with daily urinary monitoring. This paper tries to follow up the increase elimination rate of tritium in contaminated rats after administration of furosemide, a diuretic used in medical practice. The experiments has been realized on the Wistar rats divided into two groups. First, the control group was contaminated with 3 HHO by intraperitoneal (i.p.) inoculation. The second group was treated with 3 doses of 5.70 mg furosemide (i.p.) body weight at 2, 6 and 12 hours after i.p. inoculation with 3 HHO. Following exposure, the tritium elimination in excreta was monitored 18 days and blood, liver, muscle and kidney were extracted from rats at 1, 2, 4, 7, 11, 18 days after contamination. The excreta and tissues were analyzed with specific tritium radiochemical methods and the samples radioactivity was measured by liquid scintillation technique. Efficiency of treatment was about 30 %. (authors)

  6. Impact of oral supplementation of Glutamate and GABA on memory performance and neurochemical profile in hippocampus of rats.

    Science.gov (United States)

    Tabassum, Saiqa; Ahmad, Saara; Madiha, Syeda; Khaliq, Saima; Shahzad, Sidrah; Batool, Zehra; Haider, Saida

    2017-05-01

    Glutamate (GLU) and gamma-amino butyric acid (GABA) are essential amino acids (AA) for brain function serving as excitatory and inhibitory neurotransmitter respectively. Their tablets are available in market for improving gut function and muscle performance. Despite of having a major role during memory formation and processing, effects of these tablets on brain functioning like learning and memory have not been investigated. Therefore, present study is aimed to investigate the effects of orally supplemented GLU and GABA on learning and memory performance and further to monitor related effects of these orally supplemented GLU and GABA on brain levels of these AA. Three groups of rats were supplemented orally with drinking water (control group) or suspension of tablets of GABA and Glutamate, respectively for four weeks. Cognitive performance was determined using behavioral tests (Novel object recognition test, Morris water maze, Passive avoidance test) measuring recognition, spatial reference and aversive memory. Levels of GLU, GABA and acetylcholine (ACh) were estimated in rat hippocampus. Results showed that chronic oral administration of GLU and GABA tablets has a significant impact on brain function and can alter GLU and GABA content in rat hippocampus. Compared to GABA, GLU supplementation specifically enhances memory performance via increasing ACh. Thus, GLU can be suggested as a useful supplement for improving learning and memory performance and neurochemical status of brain and in future could be effective in the treatment of neurological disorders affecting learning and memory performance.

  7. Developmental toxicity of orally administered pineapple leaf extract in rats.

    Science.gov (United States)

    Hu, Jun; Lin, Han; Shen, Jia; Lan, Jiaqi; Ma, Chao; Zhao, Yunan; Lei, Fan; Xing, Dongming; Du, Lijun

    2011-06-01

    The extract of pineapple leaves (EPL) has anti-diabetic and anti-dyslipidemic effects and can be developed into a promising natural medicine. This study was conducted to evaluate EPL's effects on developmental parameters in order to provide evidence of its safety before potential medical use. Five groups were included: a negative control that was given distilled water daily, a positive control that was dosed 7 mg/kg cyclophosphamide (CP) every two days, and three groups that were respectively dosed 2.0, 1.0, and 0.5 g/kg EPL daily. Female rats were dosed during the organogenesis period of gestation days (GD) 7-17 and terminated on GD 20. A series of parameters were examined. Data revealed that CP significantly reduced maternal body weight gains, caused maternal organ weight alterations, reduced female fertility, disturbed fetal growth and development, and caused marked teratogenic effects on fetal appearances, skeleton and internal organs. Distilled water and the three high doses of EPL did not cause any of the aforementioned effects. This study concluded that orally administered EPL is safe to rats during embryonic development. Copyright © 2011 Elsevier Ltd. All rights reserved.

  8. Estimation of the hydrogen concentration in rat tissue using an airtight tube following the administration of hydrogen via various routes.

    Science.gov (United States)

    Liu, Chi; Kurokawa, Ryosuke; Fujino, Masayuki; Hirano, Shinichi; Sato, Bunpei; Li, Xiao-Kang

    2014-06-30

    Hydrogen exerts beneficial effects in disease animal models of ischemia-reperfusion injury as well as inflammatory and neurological disease. Additionally, molecular hydrogen is useful for various novel medical and therapeutic applications in the clinical setting. In the present study, the hydrogen concentration in rat blood and tissue was estimated. Wistar rats were orally administered hydrogen super-rich water (HSRW), intraperitoneal and intravenous administration of hydrogen super-rich saline (HSRS), and inhalation of hydrogen gas. A new method for determining the hydrogen concentration was then applied using high-quality sensor gas chromatography, after which the specimen was prepared via tissue homogenization in airtight tubes. This method allowed for the sensitive and stable determination of the hydrogen concentration. The hydrogen concentration reached a peak at 5 minutes after oral and intraperitoneal administration, compared to 1 minute after intravenous administration. Following inhalation of hydrogen gas, the hydrogen concentration was found to be significantly increased at 30 minutes and maintained the same level thereafter. These results demonstrate that accurately determining the hydrogen concentration in rat blood and organ tissue is very useful and important for the application of various novel medical and therapeutic therapies using molecular hydrogen.

  9. Estimation of the hydrogen concentration in rat tissue using an airtight tube following the administration of hydrogen via various routes

    Science.gov (United States)

    Liu, Chi; Kurokawa, Ryosuke; Fujino, Masayuki; Hirano, Shinichi; Sato, Bunpei; Li, Xiao-Kang

    2014-01-01

    Hydrogen exerts beneficial effects in disease animal models of ischemia-reperfusion injury as well as inflammatory and neurological disease. Additionally, molecular hydrogen is useful for various novel medical and therapeutic applications in the clinical setting. In the present study, the hydrogen concentration in rat blood and tissue was estimated. Wistar rats were orally administered hydrogen super-rich water (HSRW), intraperitoneal and intravenous administration of hydrogen super-rich saline (HSRS), and inhalation of hydrogen gas. A new method for determining the hydrogen concentration was then applied using high-quality sensor gas chromatography, after which the specimen was prepared via tissue homogenization in airtight tubes. This method allowed for the sensitive and stable determination of the hydrogen concentration. The hydrogen concentration reached a peak at 5 minutes after oral and intraperitoneal administration, compared to 1 minute after intravenous administration. Following inhalation of hydrogen gas, the hydrogen concentration was found to be significantly increased at 30 minutes and maintained the same level thereafter. These results demonstrate that accurately determining the hydrogen concentration in rat blood and organ tissue is very useful and important for the application of various novel medical and therapeutic therapies using molecular hydrogen. PMID:24975958

  10. Toxicological evaluation of silver nanoparticles and silver nitrate in rats following 28 days of repeated oral exposure.

    Science.gov (United States)

    Qin, Guangqiu; Tang, Song; Li, Shibin; Lu, Haoliang; Wang, Yanwu; Zhao, Peng; Li, Bin; Zhang, Jiehong; Peng, Liang

    2017-02-01

    The increasing application of silver nanoparticles (AgNPs) has been raising concerns about their potential adverse effects to human and the environment. However, the knowledge on the systemic toxicity of AgNPs in mammalian systems is still limited. The present study investigated the toxicity of PVP-coated AgNPs in rats treated with repeated oral administration, and compared that with equivalent dose of AgNO 3 . Specifically, one hundred male and female rats were orally administrated with particulate or ionic forms of silver (Ag) separately at doses of 0.5 and 1 mg kg -1 body weight daily for 28 days. The results reveal no significant toxic effects of AgNPs and AgNO 3 up to 1 mg kg -1 body weight, with respect to the body weight, organ weight, food intake, and histopathological examination. Ag distribution pattern in organs of rats treated with AgNPs was similar to that of AgNO 3 treated rats, showing liver and kidneys are the main target organs followed by testis and spleen. The total Ag contents in organs were significantly lower in the AgNPs treated rats than those in the AgNO 3 treated rats. However, the comparisons between AgNPs and AgNO 3 treatments further indicated more potent of AgNPs in biochemical and hematological parameters in rats, including red blood cell count (RBC), platelet count (PLT), white blood cell count (WBC) and aspartate transaminase (AST). Results of this study suggested that particulate Ag at least partially contributed to the observed toxicity of AgNPs, and both ionic and particulate Ag should be taken into consideration in toxicological evaluation of AgNPs. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 609-618, 2017. © 2016 Wiley Periodicals, Inc.

  11. Distribution of enrofloxacin in intestinal tissue and contents of healthy pigs after oral and intramuscular administrations

    DEFF Research Database (Denmark)

    Wiuff, C.; Lykkesfeldt, J.; Aarestrup, Frank Møller

    2002-01-01

    The concentration of enrofloxacin in plasma, intestinal tissue, lymph nodes and intestinal contents was investigated in healthy pigs after oral (p.o.) and intramuscular (i.m.) administration of a single dose of 2.5 mg/kg bw. Tissue and content samples were collected from jejunum, ileum, caecum...... administration, and maximum concentrations in tissue and plasma were determined later than after i.m. administration. No difference between route of administration was observed in the intestinal content. Enrofloxacin concentrations in faeces during a 5-day dosing regimen with i.m. and p.o. administration were....... On the basis of these results it was concluded that in order to ensure an immediate high concentration of enrofloxacin, and thereby avoid an initial selection for resistant mutants, the intramuscular route seems to be preferable to the oral route....

  12. Disposition of 2,4-dichlorophenoxyacetic acid dimethylamine by Fischer 344 rats dosed orally and dermally

    International Nuclear Information System (INIS)

    Pelletier, O.; Ritter, L.; Caron, J.; Somers, D.

    1989-01-01

    The dimethylamine salt of 14C-ring-labeled 2,4-D was administered to Fischer 344 rats orally (1 and 0.4 mg/kg body weight) and dermally (10 mg/kg body weight). Absorption, distribution, and elimination were determined from 14C-labeled 2,4-D in blood, tissues, and excreta. Quantitatively, most of the orally administered dose (94-96%) became systemically available within 6 h. Following dermal administration 10% of the dose became systemically available over 72 h. However, peak concentrations in blood and kidneys were achieved within 30 min of dosing by either route. By 1.5 h after dosing, 2,4-D concentrations in blood, muscle, liver, and kidneys had decreased in both the orally dosed and dermally dosed animals. Between 2 and 8 h, the blood, muscle, liver and kidney concentrations in dermally dosed animals maintained a plateau while urinary excretion increased, presumably due to continued absorption of 2,4-D from the skin. The concentrations in orally dosed animals continued to decrease. Following 7 h of dermal exposure, skin cleansing removed about 63% of the applied dose; about 17% of the applied dose remained at the site of dermal dosing. At 8 h, 2,4-D concentrations in blood, muscle, liver, and kidneys of dermally dosed animals began to decrease, most likely a result of the removal of the reservoir on the skin. However, 2,4-D continued to be absorbed from skin site, resulting in a slower decline of the 2,4-D concentrations in these tissues over remainder of the 72-h study period. By comparison, in animals that had been orally dosed, the absorbed dose was almost completely excreted within 24 h

  13. Pharmacokinetics of terbinafine after oral administration of a single dose to Hispaniolan Amazon parrots (Amazona ventralis).

    Science.gov (United States)

    Evans, Erika E; Emery, Lee C; Cox, Sherry K; Souza, Marcy J

    2013-06-01

    To determine pharmacokinetics after oral administration of a single dose of terbinafine hydrochloride to Hispaniolan Amazon parrots (Amazona ventralis). 6 healthy adult Hispaniolan Amazon parrots. A single dose of terbinafine hydrochloride (60 mg/kg) was administered orally to each bird, which was followed immediately by administration of a commercially available gavage feeding formula. Blood samples were collected at the time of drug administration (time 0) and 0.25, 0.5, 1, 2, 4, 8, 12, and 24 hours after drug administration. Plasma concentrations of terbinafine were determined via high-performance liquid chromatography. Data from 1 bird were discarded because of a possible error in the dose of drug administered. After oral administration of terbinafine, the maximum concentration for the remaining 5 fed birds ranged from 109 to 671 ng/mL, half-life ranged from 6 to 13.5 hours, and time to the maximum concentration ranged from 2 to 8 hours. No adverse effects were observed. Analysis of the results indicated that oral administration of terbinafine at a dose of 60 mg/kg to Amazon parrots did not result in adverse effects and may be potentially of use in the treatment of aspergillosis. Additional studies are needed to determine treatment efficacy and safety.

  14. Intraluminal Administration of Poly I:C Causes an Enteropathy That Is Exacerbated by Administration of Oral Dietary Antigen

    Science.gov (United States)

    Araya, Romina E.; Jury, Jennifer; Bondar, Constanza

    2014-01-01

    Systemic administration of polyinosinic:polycytidylic acid (poly I:C), mimics virally-induced activation of TLR3 signalling causing acute small intestine damage, but whether and how mucosal administration of poly I:C causes enteropathy is less clear. Our aim was to investigate the inflammatory pathways elicited after intraluminal administration of poly I:C and determine acute and delayed consequences of this locally induced immune activation. Intraluminal poly I:C induced rapid mucosal immune activation in C57BL/6 mice involving IFNβ and the CXCL10/CXCR3 axis, that may drive inflammation towards a Th1 profile. Intraluminal poly I:C also caused enteropathy and gut dysfunction in gliadin-sensitive NOD-DQ8 mice, and this was prolonged by concomitant oral administration of gliadin. Our results indicate that small intestine pathology can be induced in mice by intraluminal administration of poly I:C and that this is exacerbated by subsequent oral delivery of a relevant dietary antigen. PMID:24915573

  15. Orally administered whole egg demonstrates antidepressant-like effects in the forced swimming test on rats.

    Science.gov (United States)

    Nagasawa, Mao; Otsuka, Tsuyoshi; Ogino, Yumi; Yoshida, Junki; Tomonaga, Shozo; Yasuo, Shinobu; Furuse, Mitsuhiro

    2014-08-01

    Several studies have reported that vegetarian diets are associated with a higher prevalence of major depression. Therefore, we hypothesised that the consumption of animal products, especially eggs, may have positive effects on mental health, especially on major depression, because a previous study reported that egg consumption produces numerous beneficial effects in humans. The purpose of the present study was to evaluate the effects of chronic whole-egg treatment on depression-like behaviours in Wistar rats, a control strain, and Wistar Kyoto rats, an animal model of depression. In both the rats, either whole-egg solution (5 ml/kg) or distilled water (5 ml/kg) was orally administrated for 35 days. During these periods, the open-field test (OFT) was conducted on the 21st day, and a forced swimming test (FST) was enforced on the 27th and 28th days. On the 36th day, the plasma and brain were collected. Chronic whole-egg treatment did not affect line crossing in the OFT, whereas it reduced the total duration of immobility in the FST on both strains. Furthermore, interestingly, the results indicated the possibility that whole-egg treatment elevated the incorporation of tryptophan into the brain, and the tryptophan concentration in the prefrontal cortex was actually increased by the treatment. This study demonstrated that whole-egg treatment exerts an antidepressant-like effect in the FST. It is suggested that whole egg may be an excellent food for preventing and alleviating the conditions of major depression.

  16. Rapid absorption of diclofenac and acetaminophen after their oral administration to cattle.

    Science.gov (United States)

    Sawaguchi, Akiyo; Sasaki, Kazuaki; Miyanaga, Keisuke; Nakayama, Mitsuhiro; Nagasue, Masato; Shimoda, Minoru

    2016-10-01

    The oral pharmacokinetics of diclofenac (DF) were evaluated in cattle by analyzing plasma concentration-time data after its intravenous and oral administration in order to propose the oral administration of DF as effective route to avoid long withdraw period. DF was intravenously and orally administered at 1 mg/kg to cattle using a crossover design with a 4-week washout period. Plasma concentrations of DF were determined by a HPLC analysis. The mean absorption time (MAT) and absorption half-life (t 1/2ka ) were 1.61 ± 0.61 and 1.51 ± 0.38 hr, respectively, and bioavailability was nearly 100%. The oral pharmacokinetics of acetaminophen (AAP) were also evaluated in cattle. Plasma concentrations of AAP were determined by a HPLC analysis. MAT and t 1/2ka were 2.85 ± 0.93 and 1.53 ± 0.28 hr, respectively, and bioavailability was approximately 70%. In conclusion, the results of the present study indicate that DF and AAP are rapidly absorbed from the forestomach of cattle. Therefore, the appropriate efficacies of these drugs may be achieved via their oral administration, even in cattle.

  17. Disruption of spindle checkpoint function in rats following 28 days of repeated administration of renal carcinogens.

    Science.gov (United States)

    Kimura, Masayuki; Mizukami, Sayaka; Watanabe, Yousuke; Hasegawa-Baba, Yasuko; Onda, Nobuhiko; Yoshida, Toshinori; Shibutani, Makoto

    2016-02-01

    We previously reported that 28-day exposure to hepatocarcinogens that facilitate cell proliferation specifically alters the expression of G1/S checkpoint-related genes and proteins, induces aberrant early expression of ubiquitin D (UBD) at the G2 phase, and increases apoptosis in the rat liver, indicating G1/S and spindle checkpoint dysfunction. The present study aimed to determine the time of onset of carcinogen-specific cell-cycle disruption after repeated administration of renal carcinogens for up to 28 days. Rats were orally administered the renal carcinogens nitrofurantoin (NFT), 1-amino-2,4-dibromoantraquinone (ADAQ), and 1,2,3-trichloropropane (TCP) or the non-carcinogenic renal toxicants 1-chloro-2-propanol, triamterene, and carboxin for 3, 7 or 28 days. Both immunohistochemical single-molecule analysis and real-time RT-PCR analysis revealed that carcinogen-specific expression changes were not observed after 28 days of administration. However, the renal carcinogens ADAQ and TCP specifically reduced the number of cells expressing phosphorylated-histone H3 at Ser10 in both UBD(+) cells and proliferating cells, suggestive of insufficient UBD expression at the M phase and early transition of proliferating cells from the M phase, without increasing apoptosis, after 28 days of administration. In contrast, NFT, which has marginal carcinogenic potential, did not induce such cellular responses. These results suggest that it may take 28 days to induce spindle checkpoint dysfunction by renal carcinogens; however, induction of apoptosis may not be essential. Thus, induction of spindle checkpoint dysfunction may be dependent on carcinogenic potential of carcinogen examined, and marginal carcinogens may not exert sufficient responses even after 28 days of administration.

  18. Comparison of oral versus rectal administration of acetaminophen with codeine in postoperative pediatric adenotonsillectomy patients.

    Science.gov (United States)

    Owczarzak, Vicki; Haddad, Joseph

    2006-08-01

    To examine whether acetaminophen with codeine administered per rectum is an effective alternative for pain control compared with oral administration after an adenotonsillectomy. A prospective, randomized control study. Seventy-five children aged 1 to 5 were recruited for this study. Each child was assigned randomly to receive either rectal or oral postoperative pain medication. A journal with eight questions was kept for 10 days after the operation, and an overall survey of five questions was filled out at the first postoperative visit. Postoperative pain was adequately controlled in those patients receiving suppositories when compared with those patients receiving oral pain medication. Adverse effects and total number of doses given per day were similar. Parents found the suppositories easy to administer, and more parents would switch or consider switching from oral pain medication to suppositories if given the choice. The suppositories achieved equivalent pain control as oral medication with few side effects and good tolerance. Furthermore, many parents preferred the suppositories to oral medication in maintaining postoperative pain control because of ease of administration. If given the choice for future surgeries, many parents would switch or consider switching from oral pain medication to suppositories.

  19. Nursing Administrators' Views on Oral Health in Long-Term Care Facilities: An exploratory study.

    Science.gov (United States)

    Urata, Janelle Y; Couch, Elizabeth T; Walsh, Margaret M; Rowe, Dorothy J

    2018-04-01

    Purpose: To explore the knowledge, attitudes, and practices of supervising nurse administrators (SNAs) regarding the oral care provided to long-term care facility (LTCF) residents and the role of dental professionals in those facilities. Methods: The investigators of this study partnered with the National Association of Nursing Administrators to send this cross-sectional study consisting of a 35-item electronic survey to its members whose email addresses were in their database. Online software tabulated responses and calculated frequencies (percentages) of responses for each survey item. Results: Of the 2,359 potential participants, 171 (n=171) completed the survey for a 7% response rate. Only 25% of the respondents were familiar with the expertise of dental hygienists (DHs), however once informed, the majority were interested in having DHs perform oral health staff trainings, oral screenings, and dental referrals and initiate fluoride varnish programs. Most respondents correctly answered the oral health-related knowledge items, understood that oral health is important to general health, but reported that the LTCF residents' oral health was only "good" or "fair." Fewer than half, (48%) of the SNAs were "very satisfied" with the quality of oral care provided to the residents. While more than half reported that they had no dentist on staff or on-site dental equipment, 77% reported that they would consider on-site mobile oral care services. Oral health training for staff was provided primarily by registered nurses, however only 32% reported including identification of dental caries as part of the in-service training. Conclusion: This exploratory study lays the foundation for more extensive research investigating various strategies to improve the oral health of LTCF residents, including increased collaboration between DHs and SNAs. Copyright © 2018 The American Dental Hygienists’ Association.

  20. Urinary profile of methylprednisolone and its metabolites after oral and topical administrations.

    Science.gov (United States)

    Matabosch, Xavier; Pozo, Oscar J; Monfort, Núria; Pérez-Mañá, Clara; Farré, Magi; Marcos, Josep; Segura, Jordi; Ventura, Rosa

    2013-11-01

    Methylprednisolone (MP) is prohibited in sports competitions when administered by systemic routes; however its use by topical administration is allowed. Therefore, analytical approaches to distinguish between these different administration pathways are required. A reporting level of 30ng/mL was established for this purpose. However, the suitability of that reporting level for MP is not known. In the present work, excretion profiles of MP and different metabolites after oral and topical administrations have been compared. A method for the quantification of MP and the qualitative detection of fifteen previously reported metabolites has been validated. The method involved an enzymatic hydrolysis, liquid-liquid extraction and analysis by liquid chromatography coupled to tandem mass spectrometry. The method was found to be linear, selective, precise and accurate. The high sensitivity (limit of detection 0.1ng/mL) and linear range (0.1-250ng/mL) achieved allowed for the quantification of MP at both the low concentrations present after topical administration and the high concentrations detected after oral intake. The method was applied to samples collected after oral (4 or 40mg) and topical administration (10mg of MP aceponate/day for 5 consecutive days) to healthy volunteers. After oral administration, MP and all metabolites were detected in urines collected up to at least 36h. Only MP and five metabolites were detected in samples obtained after topical treatment. As expected, concentrations of MP after topical administration were well below current reporting level (30ng/mL), however 3 out of 4 samples in range 8-24h after the low oral dose (4mg) were also below that concentration. Taking into account metabolites detected after both administration routes, metabolites 16β,17α,21-trihydroxy-6α-methylpregna-1,4-diene-3,11,20-trione (M8) and 17α,20α,21-trihydroxy-6α-methylpregna-1,4-diene-3,11-dione (M11) are best markers to differentiate between topical and oral

  1. Pharmacokinetics of S-Allyl-l-cysteine in Rats Is Characterized by High Oral Absorption and Extensive Renal Reabsorption.

    Science.gov (United States)

    Amano, Hirotaka; Kazamori, Daichi; Itoh, Kenji

    2016-02-01

    S-Allylcysteine (SAC) is a key component of aged garlic extract, one of many garlic products. However, information on its pharmacokinetics has been scant except for data from a few animal studies. We designed this study to determine the overall pharmacokinetics of SAC in rats. After oral or intravenous administration of SAC to rats at a dose of 5 mg/kg, the plasma concentration-time profile of SAC and its metabolites, as well as the amounts excreted in bile and urine, were analyzed by using liquid chromatography tandem mass spectrometry. After oral administration, SAC was well absorbed with a bioavailability of 98%. Two major metabolites of SAC, N-acetyl-S-allylcysteine (NAc-SAC) and N-acetyl-S-allylcysteine sulfoxide (NAc-SACS), were detected in plasma, but their concentrations were markedly lower than those of SAC. SAC was metabolized to a limited extent, but most of the orally absorbed SAC was excreted into urine in the form of its N-acetylated metabolites. The amounts of SAC, NAc-SAC, and NAc-SACS excreted in urine over 24 h were 2.9%, 80%, and 11% of the orally administered SAC, respectively. The very low renal clearance (0.016 L ⋅ h(-1) ⋅ kg(-1)) of SAC indicated that it undergoes extensive renal reabsorption. These results collectively suggested that SAC was ultimately metabolized to NAc-SAC and NAc-SACS through the cycles of urinary excretion, renal reabsorption, and systemic recirculation. The pharmacokinetics of SAC in rats were characterized by high oral absorption, limited metabolism, and extensive renal reabsorption, all of which potentially contribute to its high and relatively long-lasting plasma concentrations. © 2016 American Society for Nutrition.

  2. Acute and Sub-Acute Oral Toxicity Evaluation of Astragalus hamosus Seedpod Ethanolic Extract in Wistar Rats

    Directory of Open Access Journals (Sweden)

    Mohammadmehdi Hassanzadeh-Taheri

    2018-03-01

    Full Text Available Background: Oral consumption of Astragalus hamosus L. (AH seedpod has been widely prescribed in traditional medicine system. However, its toxicity evaluation has never been investigated. Hence, the current study was performed to evaluate the toxicological profile of AH seedpod in acute and subacute assessments based on the OECD-guidelines 425 and 407 in male and female Wistar rats. Methods: In the acute study, ethanolic extract of AH at a single dose of 2000 mg/kg was orally administrated to six female rats. In the subacute assay, AH at the three different oral doses (75, 150 and 300 mg/kg were administrated to both male and female rats for 28 consecutive days. Results: No death or behavioural changes were observed in the treated animals. In subacute test, in both sexes, no changes in organ weights observed. Biochemically, compared to the control, AH at the dose of 300 mg/kg slightly increased (p<0.05 uric acid and creatinine and declined total cholesterol levels in both male and female rats. However, there is no statistically difference in other parameters such as albumin, triglyceride, blood urea, aspartate aminotransferase and alanine aminotransferase between AH treated groups and untreated controls. Hematologic parameters showed that AH at the maximum dose decreased red blood cells count only in male rats. Histopathological evaluation of liver and kidney exhibited no noticeable alterations in AH treated animals. Conclusion: It could be concluded that high excessive and long term consumption of AH may lead to renal dysfunction and deficiency in hematopoietic system.

  3. [Morphine self-administration by rats using a pneumatic syringe].

    Science.gov (United States)

    Akiyama, Y; Takayama, S

    1988-06-01

    An apparatus for drug self-administration by rats using a pneumatic syringe was developed by Weeks. A microliter syringe operated by a pneumatic cylinder supplies an accurate volume of drug solution within one second. When coefficient of variation of infusion volume was compared among pneumatic syringe, infusion pump, and peristaltic pump, pneumatic syringe showed higher accuracy in infusion volume than the other two pumps. Since the infusion speed by a pneumatic syringe is very rapid (less than one second per infusion), the effect of infusion speed on reinforcing property of morphine was investigated. When rats self-administered 0.1, 0.3, 1.0, and 3.0 mg/kg/infusion of morphine by pneumatic syringes, the patterns of self-infusion were more stable, the number of self-infusions and the amount self-administered were larger, and a dose-response relationship was clearer in comparison with those self-infused the same doses of morphine for 5.6 seconds by infusion pumps or peristaltic pumps.

  4. Pharmacokinetics of morphine-6-glucuronide following oral administration in healthy volunteers

    DEFF Research Database (Denmark)

    Villesen, Hanne H.; Kristensen, Kim; Hansen, Steen Honoré

    2007-01-01

    After oral administration, morphine-6-glucuronide (M6G) displays an atypical absorption profile with two peak plasma concentrations. A proposed explanation is that M6G is hydrolysed to morphine in the colon, which is then absorbed and subsequently undergoes metabolism in the liver to morphine-3-g......-glucuronide (M3G) and M6G. The aims of this study were to confirm and elucidate the biphasic absorption profile as well as clarify the conversion of M6G to morphine after a single oral administration of M6G in healthy volunteers....

  5. Flurbiprofen concentration in soft tissues is higher after topical application than after oral administration

    Science.gov (United States)

    Kai, Shuken; Kondo, Eiji; Kawaguchi, Yasuyuki; Kitamura, Nobuto; Yasuda, Kazunori

    2013-01-01

    Aim To compare tissue concentrations of flurbiprofen resulting from topical application and oral administration according to the regulatory approved dosing guidelines. Method Sixteen patients were included in this study. Each patient was randomly assigned to the topical application or oral administration group. In each group, a pair of tapes or a tablet, containing a total of 40 mg flurbiprofen, was administered twice at 16 and 2 h before the surgery. Results The flurbiprofen concentration in the fat, tendon, muscle and periosteum tissues was significantly higher (P flurbiprofen to the human body, particularly to soft tissues near the body surface. PMID:22822928

  6. Fenofibrate Administration Reduces Alcohol and Saccharin Intake in Rats: Possible Effects at Peripheral and Central Levels

    Directory of Open Access Journals (Sweden)

    Mario Rivera-Meza

    2017-07-01

    Full Text Available We have previously shown that the administration of fenofibrate to high-drinker UChB rats markedly reduces voluntary ethanol intake. Fenofibrate is a peroxisome proliferator-activated receptor alpha (PPARα agonist, which induces the proliferation of peroxisomes in the liver, leading to increases in catalase levels that result in acetaldehyde accumulation at aversive levels in the blood when animals consume ethanol. In these new studies, we aimed to investigate if the effect of fenofibrate on ethanol intake is produced exclusively in the liver (increasing catalase and systemic levels of acetaldehyde or there might be additional effects at central level. High drinker rats (UChB were allowed to voluntary drink 10% ethanol for 2 months. Afterward, a daily dose of fenofibrate (25, 50 or 100 mg/kg/day or vehicle (as control was administered orally for 14 days. Voluntary ethanol intake was recorded daily. After that time, animals were deprived of ethanol access for 24 h and administered with an oral dose of ethanol (1 g/kg for acetaldehyde determination in blood. Fenofibrate reduced ethanol voluntary intake by 60%, in chronically drinking rats, at the three doses tested. Acetaldehyde in the blood rose up to between 80 μM and 100 μM. Considering the reduction of ethanol consumption, blood acetaldehyde levels and body weight evolution, the better results were obtained at a dose of 50 mg fenofibrate/kg/day. This dose of fenofibrate also reduced the voluntary intake of 0.2% saccharin by 35% and increased catalase levels 2.5-fold in the liver but showed no effects on catalase levels in the brain. To further study if fenofibrate administration changes the motivational properties of ethanol, a conditioned-place preference experiment was carried out. Animals treated with fenofibrate (50 mg/kg/day did not develop ethanol-conditioned place preference (CPP.In an additional experiment, chronically ethanol-drinking rats underwent two cycles of ethanol

  7. Pharmacokinetic profile and oral bioavailability of Kaurenoic acid from Copaifera spp. in rats.

    Science.gov (United States)

    Matos, Dalyara Mendonça de; Viana, Milainy Rocha; Alvim, Marcela Cristina de Oliveira; Carvalho, Lara Soares Aleixo de; Leite, Laura Hora Rios; Da Silva Filho, Ademar Alves; Nascimento, Jorge Willian Leandro

    2018-05-14

    Kaurenoic acid (KA) is a kaurane diterpene found in several medicinal plants that displays biological activities, such as anti-inflammatory, smooth muscle relaxant and hypotensive response. However, there are no pharmacokinetic data available about this molecule. The purpose of the study was to determine the pharmacokinetic profile and the oral bioavailability of KA in rats. Wistar rats submitted to jugular vein cannulation received 50 mg/kg of KA by intravenous or oral route. The implanted cannula allowed intravenous administration and serial blood collection along 10 h. Analytical quantification was performed by reversed phase HPLC-UV and mobile phase composed by acetonitrile:acidified water (70:30 v/v). The validated analytical method showed precision, accuracy, robustness, reliability and linearity between 0.75 and 100 μg/mL. KA administered intravenously showed a linear and two-compartment kinetic behavior at the tested dose. The following pharmacokinetic parameters were determined: C max  = 22.17 ± 1.65 mg/L; V = 14.53 ± 1.47 L/kg; CL = 17.67 ± 1.50 mL/min/kg; AUC 0-∞  = 2859.65 ± 278.42 mg·min/L, K = 0.073 ± 0.005 h -1 and t 1/2β  = 9.52 ± 0.61 h. Oral treatment did not provide detectable plasma levels of KA, avoiding the determination of its bioavailability. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Experimental study, in rat wistar, of cadmium distribution and elimination as a function of administration route. Cadmium 109 maximum permissible concentration

    International Nuclear Information System (INIS)

    Valero, Marc.

    1979-01-01

    The absorption and the elimination of cadmium have been investigated in rats wistar after oral administration or after inhalation. Before studying gastro-intestinal absorption, it appeared necessary to precise acute toxicity of orally administred cadmium. The distribution of cadmium within organes was determined following a single or multiple oral doses, and we specially studied retention of a Cd dose ingested after several weeks of treatment with Cd-Acetate. Pulmonary and gastro-intestinal absorption of cadmium after ihalation of Cd-microparticles were studied. Data obtained from these studies on rats and extrapolated to man were used to calculate mximum permissible concentration (M.P.C.) of Cd-109 in water and in air [fr

  9. Influence of B-Complex Vitamins on the Pharmacokinetics of Ginsenosides Rg1, Rb1, and Ro After Oral Administration.

    Science.gov (United States)

    Zheng, Peihe; Chen, Yinbin; Fu, Yangyang; Wang, Hecheng; Wang, Jia; Zheng, Siwen; Xiao, Shengyuan; Wang, Yingping

    2017-11-01

    After cultivation of ginseng, ginsenosides, which are the major active ingredients of gingeng, were approved for use by the food industry, and began to be used as added functional ingredients to try to improve the quality and price of functional foods. However, the interaction between different types of ginsenosides and nutrients needs further study. We investigated the effect of B-complex vitamins (which are essential nutrients) on the pharmacokinetics of the ginsenosides protopanaxatriol-type saponin Rg 1 , protopanaxadiol-type saponin Rb 1 , and oleanolic acid-type saponin Ro after oral administration. Ginsenosides Rg 1 , Rb 1 , and Ro, with or without B-complex vitamins, respectively, were administered orally to rats to evaluate their pharmacokinetics. The concentration of ginsenosides in plasma was determined by liquid chromatography/tandem mass spectrometry. Pharmacokinetic parameters were fitted using WinNonlin v6.2. After oral coadministration with B-complex vitamins, the area under the concentration-time curve from zero to infinity (AUC 0-∞ ) of ginsenoside Rg 1 was reduced by 70%, that of ginsenoside Rb 1 was reduced by 43%, and that of ginsenoside Ro was reduced by 34%. The AUC 0-∞ of ginsenosides Rg 1 and Rb 1 showed significant differences between different treatments, but the AUC 0-∞ of ginsenoside Ro did not. These results suggest significant ginsenoside-nutrient interactions between ginsenosides Rg 1 , Rb 1 , and B-complex vitamins.

  10. Locomotor activity: A distinctive index in morphine self-administration in rats

    OpenAIRE

    Zhang, Jian-Jun; Kong, Qingyao

    2017-01-01

    Self-administration of addictive drugs is a widely used tool for studying behavioral, neurobiological, and genetic factors in addiction. However, how locomotor activity is affected during self-administration of addictive drugs has not been extensively studied. In our present study, we tested the locomotor activity levels during acquisition, extinction and reinstatement of morphine self-administration in rats. We found that compared with saline self-administration (SA), rats that trained with ...

  11. Systemic administration of erythropoietin inhibits retinopathy in RCS rats.

    Directory of Open Access Journals (Sweden)

    Weiyong Shen

    Full Text Available OBJECTIVE: Royal College of Surgeons (RCS rats develop vasculopathy as photoreceptors degenerate. The aim of this study was to examine the effect of erythropoietin (EPO on retinopathy in RCS rats. METHODS: Fluorescein angiography was used to monitor retinal vascular changes over time. Changes in retinal glia and vasculature were studied by immunostaining. To study the effects of EPO on retinal pathology, EPO (5000 IU/kg was injected intraperitoneally in 14 week old normal and RCS rats twice a week for 4 weeks. Changes in the retinal vasculature, glia and microglia, photoreceptor apoptosis, differential expression of p75 neurotrophin receptor (p75NTR, pro-neurotrophin 3 (pro-NT3, tumour necrosis factor-α (TNFα, pigment epithelium derived factor (PEDF and vascular endothelial growth factor-A (VEGF-A, the production of CD34(+ cells and mobilization of CD34(+/VEGF-R2(+ cells as well as recruitment of CD34(+ cells into the retina were examined after EPO treatment. RESULTS: RCS rats developed progressive capillary dropout and subretinal neovascularization which were accompanied by retinal gliosis. Systemic administration of EPO stabilized the retinal vasculature and inhibited the development of focal vascular lesions. Further studies showed that EPO modulated retinal gliosis, attenuated photoreceptor apoptosis and p75NTR and pro-NT3 upregulation, promoted the infiltration of ramified microglia and stimulated VEGF-A expression but had little effect on TNFα and PEDF expression. EPO stimulated the production of red and white blood cells and CD34(+ cells along with effective mobilization of CD34(+/VEGF-R2(+ cells. Immunofluorescence study demonstrated that EPO enhanced the recruitment of CD34+ cells into the retina. CONCLUSIONS: Our results suggest that EPO has therapeutic potentials in treatment of neuronal and vascular pathology in retinal disease. The protective effects of EPO on photoreceptors and the retinal vasculature may involve multiple

  12. Metabolomic Analysis of Blood Plasma after Oral Administration of N-acetyl-d-Glucosamine in Dogs

    Directory of Open Access Journals (Sweden)

    Tomohiro Osaki

    2015-08-01

    Full Text Available N-acetyl-d-glucosamine (GlcNAc is a monosaccharide that polymerizes linearly through (1,4-β-linkages. GlcNAc is the monomeric unit of the polymer chitin. GlcNAc is a basic component of hyaluronic acid and keratin sulfate found on the cell surface. The aim of this study was to examine amino acid metabolism after oral GlcNAc administration in dogs. Results showed that plasma levels of ectoine were significantly higher after oral administration of GlcNAc than prior to administration (p < 0.001. To our knowledge, there have been no reports of increased ectoine concentrations in the plasma. The mechanism by which GlcNAc administration leads to increased ectoine plasma concentration remains unclear; future studies are required to clarify this mechanism.

  13. Pharmacokinetics and selected pharmacodynamics of trazodone following intravenous and oral administration to horses undergoing fitness training.

    Science.gov (United States)

    Knych, Heather K; Mama, Khursheed R; Steffey, Eugene P; Stanley, Scott D; Kass, Philip H

    2017-10-01

    OBJECTIVE To measure concentrations of trazodone and its major metabolite in plasma and urine after administration to healthy horses and concurrently assess selected physiologic and behavioral effects of the drug. ANIMALS 11 Thoroughbred horses enrolled in a fitness training program. PROCEDURES In a pilot investigation, 4 horses received trazodone IV (n = 2) or orally (2) to select a dose for the full study; 1 horse received a vehicle control treatment IV. For the full study, trazodone was initially administered IV (1.5 mg/kg) to 6 horses and subsequently given orally (4 mg/kg), with a 5-week washout period between treatments. Blood and urine samples were collected prior to drug administration and at multiple time points up to 48 hours afterward. Samples were analyzed for trazodone and metabolite concentrations, and pharmacokinetic parameters were determined; plasma drug concentrations following IV administration best fit a 3-compartment model. Behavioral and physiologic effects were assessed. RESULTS After IV administration, total clearance of trazodone was 6.85 ± 2.80 mL/min/kg, volume of distribution at steady state was 1.06 ± 0.07 L/kg, and elimination half-life was 8.58 ± 1.88 hours. Terminal phase half-life was 7.11 ± 1.70 hours after oral administration. Horses had signs of aggression and excitation, tremors, and ataxia at the highest IV dose (2 mg/kg) in the pilot investigation. After IV drug administration in the full study (1.5 mg/kg), horses were ataxic and had tremors; sedation was evident after oral administration. CONCLUSIONS AND CLINICAL RELEVANCE Administration of trazodone to horses elicited a wide range of effects. Additional study is warranted before clinical use of trazodone in horses can be recommended.

  14. Development of Alginate Microspheres Containing Chuanxiong for Oral Administration to Adult Zebrafish

    Directory of Open Access Journals (Sweden)

    Li-Jen Lin

    2016-01-01

    Full Text Available Oral administration of Traditional Chinese Medicine (TCM by patients is the common way to treat health problems. Zebrafish emerges as an excellent animal model for the pharmacology investigation. However, the oral delivery system of TCM in zebrafish has not been established so far. This issue was addressed by development of alginate microparticles for oral delivery of chuanxiong, a TCM that displays antifibrotic and antiproliferative effects on hepatocytes. The delivery microparticles were prepared from gelification of alginate containing various levels of chuanxiong. The chuanxiong-encapsulated alginate microparticles were characterized for their solubility, structure, encapsulation efficiency, the cargo release profile, and digestion in gastrointestinal tract of zebrafish. Encapsulation of chuanxiong resulted in more compact structure and the smaller size of microparticles. The release rate of chuanxiong increased for alginate microparticles carrying more chuanxiong in simulated intestinal fluid. This remarkable feature ensures the controlled release of encapsulated cargos in the gastrointestinal tract of zebrafish. Moreover, chuanxiong-loaded alginate microparticles were moved to the end of gastrointestinal tract after oral administration for 6 hr and excreted from the body after 16 hr. Therefore, our developed method for oral administration of TCM in zebrafish is useful for easy and rapid evaluation of the drug effect on disease.

  15. Permeability enhancers dramatically increase zanamivir absolute bioavailability in rats: implications for an orally bioavailable influenza treatment.

    Directory of Open Access Journals (Sweden)

    Eric H Holmes

    Full Text Available We have demonstrated that simple formulations composed of the parent drug in combination with generally regarded as safe (GRAS permeability enhancers are capable of dramatically increasing the absolute bioavailability of zanamivir. This has the advantage of not requiring modification of the drug structure to promote absorption, thus reducing the regulatory challenges involved in conversion of an inhaled to oral route of administration of an approved drug. Absolute bioavailability increases of up to 24-fold were observed when Capmul MCM L8 (composed of mono- and diglycerides of caprylic/capric acids in glycerol was mixed with 1.5 mg of zanamivir and administered intraduodenally to rats. Rapid uptake (t(max of 5 min and a C(max of over 7200 ng/mL was achieved. Variation of the drug load or amount of enhancer demonstrated a generally linear variation in absorption, indicating an ability to optimize a formulation for a desired outcome such as a targeted C(max for enzyme saturation. No absorption enhancement was observed when the enhancer was given 2 hr prior to drug administration, indicating, in combination with the observed tmax, that absorption enhancement is temporary. This property is significant and aligns well with therapeutic applications to limit undesirable drug-drug interactions, potentially due to the presence of other poorly absorbed polar drugs. These results suggest that optimal human oral dosage forms of zanamivir should be enteric-coated gelcaps or softgels for intraduodenal release. There continues to be a strong need and market for multiple neuraminidase inhibitors for influenza treatment. Creation of orally available formulations of inhibitor drugs that are currently administered intravenously or by inhalation would provide a significant improvement in treatment of influenza. The very simple GRAS formulation components and anticipated dosage forms would require low manufacturing costs and yield enhanced convenience. These results

  16. Effect of epidermal growth factor against radiotherapy-induced oral mucositis in rats

    International Nuclear Information System (INIS)

    Lee, Sang-wook; Jung, Kwon Il; Kim, Yeun Wha B.S.; Jung, Heun Don; Kim, Hyun Sook; Hong, Joon Pio

    2007-01-01

    Purpose: We tested the efficacy of oral recombinant human epidermal growth factor (rhEGF) against radiation-induced oral mucositis in a rat model. Methods and Materials: Each of 35 Sprague-Dawley rats, 7 to 8 weeks of age and weighing 178 ± 5 grams, was irradiated once in the head region with 25 Gy, using a 4-MV therapeutic linear accelerator at a rate of 2 Gy/min. The irradiated rats were randomly divided into four groups: those receiving no treatment (Group 1), those treated with vehicle only three times per day (Group 2), and those treated with 50 μg/mL (Group 3), or 100 μg/mL (Group 4) rhEGF three times per day. Results: Rats were monitored for survival rate and daily activity, including hair loss, sensitivity, and anorexia. We found that survival rate and oral intake were significantly increased and histologic changes were significantly decreased in the rhEGF-treated rats. There was no difference, however, between rats treated with 50 μg/mL or 100 μg/mL rhEGF. Conclusion: These findings suggest that orally administered rhEGF decreased radiation-induced oral mucositis in rats

  17. Two cases of "cannabis acute psychosis" following the administration of oral cannabis

    Directory of Open Access Journals (Sweden)

    Pin Marie

    2005-04-01

    Full Text Available Abstract Background Cannabis is the most commonly used illegal drug and its therapeutic aspects have a growing interest. Short-term psychotic reactions have been described but not clearly with synthetic oral THC, especially in occasional users. Case presentations We report two cases of healthy subjects who were occasional but regular cannabis users without psychiatric history who developed transient psychotic symptoms (depersonalization, paranoid feelings and derealisation following oral administration of cannabis. In contrast to most other case reports where circumstances and blood concentrations are unknown, the two cases reported here happened under experimental conditions with all subjects negative for cannabis, opiates, amphetamines, cocaine, benzodiazepines and alcohol, and therefore the ingested dose, the time-events of effects on behavior and performance as well as the cannabinoid blood levels were documented. Conclusion While the oral route of administration achieves only limited blood concentrations, significant psychotic reactions may occur.

  18. Intravenous or oral administration of vinorelbine in adjuvant chemotherapy with cisplatin and vinorelbine for resected NSCLC

    DEFF Research Database (Denmark)

    Sorensen, Steffen Filskov; Carus, Andreas; Meldgaard, Peter

    2015-01-01

    OBJECTIVES: Cisplatin and vinorelbine given intravenously is a well-established adjuvant chemotherapy regimen after surgery for early-stage NSCLC. Vinorelbine can also be administered orally. However, the efficacy of orally administrated vinorelbine in adjuvant treatment of NSCLC is unknown. We...... University Hospital (Denmark) from 2005 to 2012 for adjuvant chemotherapy after surgery for NSCLC. RESULTS AND CONCLUSION: Of the 265 patients included in this study, 126 patients received i.v. and 139 received p.o. vinorelbine/cisplatin. The two groups were comparable with respect to important baseline....... In conclusion we observed that intravenous or oral administration of vinorelbine in combination with cisplatin after surgery for NSCLC appear equally effective in terms of overall and disease-free survival....

  19. The effects of prolonged oral administration of gold nanoparticles on the morphology of hematopoietic and lymphoid organs

    Science.gov (United States)

    Bucharskaya, Alla B.; Pakhomy, Svetlana S.; Zlobina, Olga V.; Maslyakova, Galina N.; Navolokin, Nikita A.; Matveeva, Olga V.; Khlebtsov, Boris N.; Bogatyrev, Vladimir A.; Khlebtsov, Nikolai G.; Tuchin, Valery V.

    2017-02-01

    Currently, the usage of gold nanoparticles as photosensitizers and immunomodulators for plasmonic photothermal therapy has attracted a great attention of researches and end-users. In our work, the influence of prolonged peroral administration of gold nanoparticles (GNPs) with different sizes on the morphological changes of hematopoietic and lymphoid organs was investigated. The 24 white outbred male rats weighing 180-220 g were randomly divided into groups and administered orally for 30 days the suspension of gold nanospheres with diameters of 2, 15 and 50 nm at a dosage of 190 μg/kg of animal body weight. To prevent GNPs aggregation in a tissue and enhance biocompatibility, they were functionalized with thiolated polyethylene glycol. The withdrawal of the animals from the experiment and sampling of spleen, lymph nodes and bone marrow tissues for morphological study were performed a day after the last administration. In the spleen the boundary between the red and white pulp was not clearly differ in all experimental groups, lymphoid follicles were significantly increased in size, containing bright germinative centers represented by large blast cells. The stimulation of lymphocyte and myelocytic series of hematopoiesis was recorded at morphological study of the bone marrow. The number of immunoblasts and large lymphocytes was increased in all structural zones of lymph nodes. The more pronounced changes were found in the group with administration of 15 nm nanoparticles. Thus, the morphological changes of cellular components of hematopoietic organs have size-dependent character and indicate the activation of the migration, proliferation and differentiation of immune cells after prolonged oral administration of GNPs.

  20. Calcium metabolism in children suffering from homozygous β-thalassaemia after oral administration of 47Ca

    International Nuclear Information System (INIS)

    Liakakos, D.; Vlachos, P.; Anoussakis, C.; Constantinides, C.; Tsakalosos, I.; Alexandra Hospital, Athens

    1976-01-01

    The study of calcium metabolism in ten thalassaemic children comperatively with controls after oral administration of 47 Ca has shown diminished intestinal absorption. It is suggested that this finding is propably related in part with the pathogenesis of the osteoporosis in thalassaemia. (orig.) [de

  1. COMPARATIVE METABOLISM OF ARSENIC IN MICE AFTER A SINGLE OR REPEATED ORAL ADMINISTRATION OF ARSENATE

    Science.gov (United States)

    COMPARATIVE METABOLISM OF ARSENIC IN MICE AFTER A SINGLE OR REPEATED ORAL ADMINISTRATION OF ARSENATEMichael F. Hughes*1, Elaina M. Kenyon1, Brenda C. Edwards1, Carol T. Mitchell1, Luz Maria Del Razo2 and David J. Thomas11US EPA, ORD, NHEERL, ETD, PKB, Research Triangle Pa...

  2. (-)-Epicatechin administration and exercising skeletal muscle vascular control and microvascular oxygenation in healthy rats.

    Science.gov (United States)

    Copp, Steven W; Inagaki, Tadakatsu; White, Michael J; Hirai, Daniel M; Ferguson, Scott K; Holdsworth, Clark T; Sims, Gabrielle E; Poole, David C; Musch, Timothy I

    2013-01-15

    Consumption of the dietary flavanol (-)-epicatechin (EPI) is associated with enhanced endothelial function and augmented skeletal muscle capillarity and mitochondrial volume density. The potential for EPI to improve peripheral vascular function and muscle oxygenation during exercise is unknown. We tested the hypothesis that EPI administration in healthy rats would improve treadmill exercise performance secondary to elevated skeletal muscle blood flow and vascular conductance [VC, blood flow/mean arterial pressure (MAP)] and improved skeletal muscle microvascular oxygenation. Rats received water (control, n = 12) or 4 mg/kg EPI (n = 12) via oral gavage daily for 24 days. Exercise endurance capacity and peak O(2) uptake (Vo(2) peak) were measured via treadmill runs to exhaustion. MAP (arterial catheter) and blood flow (radiolabeled microspheres) were measured and VC was calculated during submaximal treadmill exercise (25 m/min, 5% grade). Spinotrapezius muscle microvascular O(2) pressure (Po(2mv)) was measured (phosphorescence quenching) during electrically induced twitch (1 Hz) contractions. In conscious rats, EPI administration resulted in lower (↓~5%) resting (P = 0.03) and exercising (P = 0.04) MAP. There were no differences in exercise endurance capacity, Vo(2) peak, total exercising hindlimb blood flow (control, 154 ± 13; and EPI, 159 ± 8 ml·min(-1)·100 g(-1), P = 0.68), or VC (control, 1.13 ± 0.10; and EPI, 1.24 ± 0.08 ml·min(-1)·100 g(-1)·mmHg(-1), P = 0.21) between groups. Following anesthesia, EPI resulted in lower MAP (↓~16%) but did not impact resting Po(2mv) or any kinetics parameters (P > 0.05 for all) during muscle contractions compared with control. EPI administration (4 mg·kg(-1)·day(-1)) improved modestly cardiovascular function (i.e., ↓MAP) with no impact on exercise performance, total exercising skeletal muscle blood flow and VC, or contracting muscle microvascular oxygenation in healthy rats.

  3. Assessment of oral toxicity and safety of pentamethylchromanol (PMCol), a potential chemopreventative agent, in rats and dogs

    International Nuclear Information System (INIS)

    Lindeblad, Matthew; Kapetanovic, Izet M.; Kabirov, Kasim K.; Detrisac, Carol J.; Dinger, Nancy; Mankovskaya, Irina; Zakharov, Alexander; Lyubimov, Alexander V.

    2010-01-01

    2,2,5,7,8-Pentamethyl-6-chromanol (PMCol) was administered by gavage in rats for 28 days at dose levels of 0, 100, 500, and 2000 mg/kg/day. PMCol administration induced decreases in body weight gains and food consumption, hepatotoxicity (increased TBILI, ALB, ALT, TP; increased relative liver weights; increased T4 and TSH), nephrotoxicity (increased BUN and BUN/CREAT, histopathology lesions), effect on lipid metabolism (increased CHOL), anemia, increase in WBC counts (total and differential), coagulation (FBGN↑and PT↓) and hyperkeratosis of the nonglandular stomach in the 2000 mg/kg/day dose group (in one or both sexes). In the 500 mg/kg/day dose group, toxicity was seen to a lesser extent. In the 100 mg/kg/day dose group, only increased CHOL (females) was observed. To assess the toxicity of PMCol in male dogs it was administered orally by capsule administration for 28 days at dose levels of 0, 50, 200 and 800 mg/kg/day (four male dogs/dose group). PMCol treatment at 800 mg/kg/day resulted in pronounced toxicity to the male dogs. Target organs of toxicity were liver and thymus. Treatment at 200 mg/kg/day resulted in toxicity consistent with slight adverse effect on the liver only. The results of the safety pharmacology study indicate that doses of 0, 50, 200 and 800 mg/kg administered orally did not have an effect on the QT interval, blood pressures and body temperatures following dosing over a 24-h recording period. Under the conditions of this study, the no-observed-adverse effect level (NOAEL) for daily oral administration of PMCol by gavage for 28 days to male rats was 100 mg/kg/day and 50 mg/kg in male dogs. In female rats, the NOAEL was not established due to statistically significant and biologically meaningful increases in CHOL level seen in the 100 mg/kg/day dose group. The results of these studies indicated that administration of PMCol at higher dose levels resulted in severe toxicity in dogs and moderate toxicity in rats, however, administration at

  4. Vagal afferents are essential for maximal resection-induced intestinal adaptive growth in orally fed rats

    DEFF Research Database (Denmark)

    Nelson, David W; Liu, Xiaowen; Holst, Jens Juul

    2006-01-01

    in mucosal mass, protein, DNA, and histology. Both systemic and perivagal capsaicin significantly attenuated by 48-100% resection-induced increases in ileal mucosal mass, protein, and DNA in rats fed orally. Villus height was significantly reduced in resected rats given capsaicin compared with vehicle...

  5. Tissue fixation and autoradiographic negative chemography in rat oral epithelium

    Energy Technology Data Exchange (ETDEWEB)

    Prime, S.S.; MacDonald, D.G. (Glasgow Dental Hospital (UK))

    1983-01-01

    The effect of routine methods of tissue fixation on autoradiographic negative chemography was investigated in adult rat palatal and tongue epithelia following the incorporation of /sup 3/H thymidine in vivo. Tissues fixed in formalin or Bouin's without acetic acid demonstrated more negative chemography than those fixed in Bouin's fluid, formol-acetic-methanol or Carnoy's solutions. These findings were associated with the lowest silver grain counts per nucleus in the formalin fixed tissues, low grain counts in tissues fixed in Bouin's without acetic acid, but the addition of acetic acid to make complete Bouin's fluid gave results similar to those following fixation with Carnoy's solution. The highest silver grain counts were obtained with tissues fixed in formol-acetic-methanol. The relationship between negative chemography and the labelling indices of tissues was unclear except where the negative chemographic effects were severe. Formalin fixed tissues showed the maximum negative chemographic effects and the lowest labelling indices. Carnoy's solution appeared to be the fixative of choice for cell kinetic studies of oral epithelium.

  6. Tissue fixation and autoradiographic negative chemography in rat oral epithelium

    International Nuclear Information System (INIS)

    Prime, S.S.; MacDonald, D.G.

    1983-01-01

    The effect of routine methods of tissue fixation on autoradiographic negative chemography was investigated in adult rat palatal and tongue epithelia following the incorporation of 3 H thymidine in vivo. Tissues fixed in formalin or Bouin's without acetic acid demonstrated more negative chemography than those fixed in Bouin's fluid, formol-acetic-methanol or Carnoy's solutions. These findings were associated with the lowest silver grain counts per nucleus in the formalin fixed tissues, low grain counts in tissues fixed in Bouin's without acetic acid, but the addition of acetic acid to make complete Bouin's fluid gave results similar to those following fixation with Carnoy's solution. The highest silver grain counts were obtained with tissues fixed in formol-acetic-methanol. The relationship between negative chemography and the labelling indices of tissues was unclear except where the negative chemographic effects were severe. Formalin fixed tissues showed the maximum negative chemographic effects and the lowest labelling indices. Carnoy's solution appeared to be the fixative of choice for cell kinetic studies of oral epithelium. (author)

  7. Oral fluid/plasma cannabinoid ratios following controlled oral THC and smoked cannabis administration.

    Science.gov (United States)

    Lee, Dayong; Vandrey, Ryan; Milman, Garry; Bergamaschi, Mateus; Mendu, Damodara R; Murray, Jeannie A; Barnes, Allan J; Huestis, Marilyn A

    2013-09-01

    Oral fluid (OF) is a valuable biological alternative for clinical and forensic drug testing. Evaluating OF to plasma (OF/P) cannabinoid ratios provides important pharmacokinetic data on the disposition of drug and factors influencing partition between matrices. Eleven chronic cannabis smokers resided on a closed research unit for 51 days. There were four 5-day sessions of 0, 30, 60, and 120 mg oral ∆(9)-tetrahydrocannabinol (THC)/day followed by a five-puff smoked cannabis challenge on Day 5. Each session was separated by 9 days ad libitum cannabis smoking. OF and plasma specimens were analyzed for THC and metabolites. During ad libitum smoking, OF/P THC ratios were high (median, 6.1; range, 0.2-348.5) within 1 h after last smoking, decreasing to 0.1-20.7 (median, 2.1) by 13.0-17.1 h. OF/P THC ratios also decreased during 5-days oral THC dosing, and after the smoked cannabis challenge, median OF/P THC ratios decreased from 1.4 to 5.5 (0.04-245.6) at 0.25 h to 0.12 to 0.17 (0.04-5.1) at 10.5 h post-smoking. In other studies, longer exposure to more potent cannabis smoke and oromucosal cannabis spray was associated with increased OF/P THC peak ratios. Median OF/P 11-nor-9-carboxy-THC (THCCOOH) ratios were 0.3-2.5 (range, 0.1-14.7) ng/μg, much more consistent in various dosing conditions over time. OF/P THC, but not THCCOOH, ratios were significantly influenced by oral cavity contamination after smoking or oromucosal spray of cannabinoid products, followed by time-dependent decreases. Establishing relationships between OF and plasma cannabinoid concentrations is essential for making inferences of impairment or other clinical outcomes from OF concentrations.

  8. Chromium VI administration induces oxidative stress in hypothalamus and anterior pituitary gland from male rats.

    Science.gov (United States)

    Nudler, Silvana I; Quinteros, Fernanda A; Miler, Eliana A; Cabilla, Jimena P; Ronchetti, Sonia A; Duvilanski, Beatriz H

    2009-03-28

    Hexavalent chromium (Cr VI)-containing compounds are known carcinogens which are present in industrial settings and in the environment. The major route of chromium exposure for the general population is oral intake. Previously we have observed that Cr VI affects anterior pituitary secretion and causes oxidative stress in vitro. The aim of the present work was to investigate if in vivo Cr VI treatment (100 ppm of Cr VI in drinking water for up 30 days) causes oxidative stress in hypothalamus and anterior pituitary gland from male rats. This treatment produced a 4-fold increase of chromium content in hypothalamus and 10-fold increase in anterior pituitary gland. Lipid peroxidation showed a significant increase in hypothalamus and anterior pituitary. Cr VI augmented superoxide dismutase activity in anterior pituitary gland and glutathione reductase activity in hypothalamus, but glutathione peroxidase and catalase activities remained unchanged in both tissues. Heme oxygenase-1 mRNA expression significantly rose in both tissues. Metallothionein 1 mRNA content increased in anterior pituitary and metallothionein 3 mRNA increased in hypothalamus. These results show, for the first time, that oral chronic administration of Cr VI produces oxidative stress on the hypothalamus and anterior pituitary gland which may affect normal endocrine function.

  9. Pharmacokinetics and skin concentrations of lincomycin after intravenous and oral administration to cats

    Directory of Open Access Journals (Sweden)

    Gabriela A. Albarellos

    2013-10-01

    Full Text Available The aim of the present study was to describe the plasma pharmacokinetic profile and skin concentrations of lincomycin after intravenous administration of a 15% solution and oral administration of 300 mg tablets at a dosing rate of 15 mg/kg to cats. Susceptibility of staphylococci (n = 31 and streptococci (n = 23 strains isolated from clinical cases was also determined. Lincomycin plasma and skin concentrations were determined by microbiological assay using Kocuria rhizophila ATCC 9341 as test microorganism. Susceptibility was established by the antimicrobial disc diffusion test. Individual lincomycin plasma concentration–time curves were analysed by a non-compartmental approach. After intravenous administration, volume of distribution, body clearance and elimination half-life were 0.97 L/kg ± 0.15 L/kg, 0.17 L/kg ± 0.06 L/h.kg and 4.20 h ± 1.12 h, respectively. After oral administration, peak plasma concentration, time of maximum plasma concentration and bioavailability were 22.52 µg/mL ± 10.97 µg/mL, 0.80 h ± 0.11 h and 81.78% ± 24.05%, respectively. Two hours after lincomycin administration, skin concentrations were 17.26 µg/mL ± 1.32 µg/mL (intravenous and 16.58 µg/mL ± 0.90 µg/mL (oral. The corresponding skin: plasma ratios were 2.08 ± 0.47 (intravenous and 1.84 ± 0.97 (oral. The majority of staphylococci and streptococci tested in this study were susceptible to lincosamides (87.09% and 69.56%, respectively. In conclusion, lincomycin administered orally at the assayed dose showed a good pharmacokinetic profile, with a long elimination half-life and effective skin concentration. Therefore, it could be a good first option for treating skin infections in cats.

  10. Cannabinoids and metabolites in expectorated oral fluid after 8 days of controlled around-the-clock oral THC administration.

    Science.gov (United States)

    Milman, Garry; Barnes, Allan J; Schwope, David M; Schwilke, Eugene W; Goodwin, Robert S; Kelly, Deana L; Gorelick, David A; Huestis, Marilyn A

    2011-08-01

    Oral fluid (OF) is an increasingly accepted matrix for drug testing programs, but questions remain about its usefulness for monitoring cannabinoids. Expectorated OF specimens (n = 360) were obtained from 10 adult daily cannabis smokers before, during, and after 37 20-mg oral Δ(9)-tetrahydrocannabinol (THC) doses over 9 days to characterize cannabinoid disposition in this matrix. Specimens were extracted and analyzed by gas chromatography-mass spectrometry with electron-impact ionization for THC, 11-hydroxy-THC, cannabidiol, and cannabinol, and negative chemical ionization for 11-nor-9-carboxy-THC (THCCOOH). Linear ranges for THC, 11-hydroxy-THC, and cannabidiol were 0.25-50 ng/mL; cannabinol 1-50 ng/mL; and THCCOOH 5-500 pg/mL. THCCOOH was the most prevalent analyte in 344 specimens (96.9%), with concentrations up to 1,390.3 pg/mL. 11-hydroxy-THC, cannabidiol, and cannabinol were detected in 1, 1, and 3 specimens, respectively. THC was detected in only 13.8% of specimens. The highest THC concentrations were obtained at admission (median 1.4 ng/mL, range 0.3-113.6) from previously self-administered smoked cannabis. A total of 2.5 and 3.7% of specimens were THC-positive at the recommended Substance Abuse and Mental Health Services Administration (2 ng/mL) and Driving Under the Influence of Drugs, Alcohol and Medicines (DRUID) (1 ng/mL) confirmation cutoffs, respectively. THC is currently the only analyte for monitoring cannabis exposure in OF; however, these data indicate chronic therapeutic oral THC administration and illicit oral THC use are unlikely to be identified with current guidelines. Measurement of THCCOOH may improve the detection and interpretation of OF cannabinoid tests and minimize the possibility of OF contamination from passive inhalation of cannabis smoke.

  11. Nanoemulsion improves the oral bioavailability of baicalin in rats: in vitro and in vivo evaluation

    Directory of Open Access Journals (Sweden)

    Zhao L

    2013-10-01

    Full Text Available Ling Zhao,1,2 Yumeng Wei,1,2 Yu Huang,1 Bing He,2 Yang Zhou,1 Junjiang Fu31Department of Pharmaceutical Sciences, School of Pharmacy, Luzhou Medical College, Luzhou City, Sichuan Province, People's Republic of China; 2Drug and Functional Food Research Center, Luzhou Medical College, Luzhou City, Sichuan Province, People's Republic of China; 3The Research Center for Preclinical Medicine, Luzhou Medical College, Luzhou City, Sichuan Province, People's Republic of ChinaAbstract: Baicalin is one of the main bioactive flavone glucuronides derived as a medicinal herb from the dried roots of Scutellaria baicalensis Georgi, and it is widely used for the treatment of fever, inflammation, and other conditions. Due to baicalin's poor solubility in water, its absolute bioavailability after oral administration is only 2.2%. The objective of this study was to develop a novel baicalin-loaded nanoemulsion to improve the oral bioavailability of baicalin. Based on the result of pseudoternary phase diagram, the nanoemulsion formulation consisting of soy-lecithin, tween-80, polyethylene glycol 400, isopropyl myristate, and water (1:2:1.5:3.75:8.25, w/w was selected for further study. Baicalin-loaded nanoemulsions (BAN-1 and BAN-2 were prepared by internal or external drug addition and in vivo and in vitro evaluations were performed. The results showed that the mean droplet size, polydispersity index, and drug content of BAN-1 and BAN-2 were 91.2 ± 2.36 nm and 89.7 ± 3.05 nm, 0.313 ± 0.002 and 0.265 ± 0.001, and 98.56% ± 0.79% and 99.40% ± 0.51%, respectively. Transmission electron microscopy revealed spherical globules and confirmed droplet size analysis. After dilution 30-fold with water, the solubilization capacity of BAN-1 and BAN-2 did not change. In vitro release results showed sustained-release characteristics. BAN-1 formulation was stable for at least 6 months and was more stable than BAN-2. In rats, the area under the plasma drug concentration

  12. The rat closely mimics oxidative stress and inflammation in humans after exercise but not after exercise combined with vitamin C administration.

    Science.gov (United States)

    Veskoukis, Aristidis S; Goutianos, Georgios; Paschalis, Vassilis; Margaritelis, Nikos V; Tzioura, Aikaterini; Dipla, Konstantina; Zafeiridis, Andreas; Vrabas, Ioannis S; Kyparos, Antonios; Nikolaidis, Michalis G

    2016-04-01

    The purpose of the present study was to directly compare oxidative stress and inflammation responses between rats and humans. We contrasted rat and human oxidative stress and inflammatory responses to exercise (pro-oxidant stimulus) and/or vitamin C (anti-oxidant stimulus) administration. Vitamin C was administered orally in both species (16 mg kg(-1) of body weight). Twelve redox biomarkers and seven inflammatory biomarkers were determined in plasma and erythrocytes pre- and post-exercise or pre- and post-exercise combined with vitamin C administration. Exercise increased oxidative stress and induced an inflammatory state in rats and humans. There were only 1/19 significant species × exercise interactions (catalase), indicating similar responses to exercise between rats and humans in redox and inflammatory biomarkers. Vitamin C decreased oxidative stress and increased antioxidant capacity only in humans and did not affect the redox state of rats. In contrast, vitamin C induced an anti-inflammatory state only in rats and did not affect the inflammatory state of humans. There were 10/19 significant species × vitamin C interactions, indicating that rats poorly mimic human oxidative stress and inflammatory responses to vitamin C administration. Exercise after acute vitamin C administration altered redox state only in humans and did not affect the redox state of rats. On the contrary, inflammation biomarkers changed similarly after exercise combined with vitamin C in both rats and humans. The rat adequately mimics human responses to exercise in basic blood redox/inflammatory profile, yet this is not the case after exercise combined with vitamin C administration.

  13. Prophylactic administration of melatonin to the mother throughout pregnancy can protect against oxidative cerebral damage in neonatal rats.

    Science.gov (United States)

    Watanabe, Kazushi; Hamada, Fumiaki; Wakatsuki, Akihiko; Nagai, Ryuhei; Shinohara, Koichi; Hayashi, Yoshihiro; Imamura, Rina; Fukaya, Takao

    2012-08-01

    The purpose of this study was to investigate whether prophylactic administration of melatonin to the mother throughout pregnancy could protect against ischemia/reperfusion (I/R)-induced oxidative brain damage in neonatal rats. The utero-ovarian arteries were occluded bilaterally for 30 min in female Wistar rats on day 16 of pregnancy to induce fetal ischemia. Reperfusion was achieved by releasing the occlusion and restoring circulation. A sham operation was performed in control rats. Melatonin solution or vehicle alone was administrated orally throughout pregnancy. We collected brain mitochondria from neonatal rats, evaluated mitochondrial structure by electron microscopy, and measured the respiratory control index (RCI) as an indicator of mitochondrial respiratory activity as well as the concentration of thiobarbituric acid-reactive substances (TBARS), a marker of oxidative stress. Histological analysis was performed at the Cornu Ammonis 1 (CA1) and Cornu Ammonis 3 (CA3) regions of the hippocampus. I/R significantly reduced the RCI and significantly elevated the concentration of TBARS. Melatonin treatment reversed these effects, resulting in values similar to that in untreated, sham-ischemic animals. Electron microscopic evaluation showed that the number of intact mitochondria decreased in the I/R group, while melatonin treatment preserved them. Histological analysis revealed a decrease in the ratio of normal to whole pyramidal cell number in the CA1 and CA3 regions in the I/R group. While melatonin administration protected against degeneration. These results indicate that prophylactic administration of melatonin to the mother throughout pregnancy may prevent I/R-induced oxidative brain damage in neonatal rats.

  14. Oral administration of Allium sativum extract protects against infectious bursal disease in chickens

    Directory of Open Access Journals (Sweden)

    Sufen ZHAO,Yuanyuan JIA,Weiwei ZHANG,Lili WANG,Yunfei MA,Kedao TENG

    2015-12-01

    Full Text Available Garlic (Allium sativum, Liliaceae has been safely used for more than 5000 years, and research on garlic extract is rapidly increasing because of its multiple biological functions. The in vivo effects of oral administration of garlic mixture (GM, water-soluble extract on infectious bursal disease virus (IBDV-infected specific pathogen free male white leghorn chicken were examined through histopathological, immunohistochemical, and Western blot analyses, and enzyme-linked immunosorbent assay. The results confirmed the protective effects of oral administration of 5 mg·kg-1 BW GM (Group GM1 on bursal lesions after IBDV infection. In particular, protein expression of IBDV in the bursa decreased in Group GM1, indicating that GM administration decreased IBDV replication in the bursa. Furthermore, immunoglobulin M- and A-bearing B lymphocytes significantly increased 7 days post infection in bursae in Group GM1 (P<0.01, suggesting that the oral administration of 5 mg·kg-1 GM offers moderate protection against B cell destruction after IBDV infection. During infection, the concentration of bursal interferon gamma (IFN-g increased and peaked in Group GM1 earlier than in Group T (IBDV-exposed, demonstrating that GM administration prompted the production of IFN-g to protect against IBDV infection.

  15. The antihypertensive effect of orally administered nifedipine-loaded nanoparticles in spontaneously hypertensive rats.

    Science.gov (United States)

    Kim, Y I; Fluckiger, L; Hoffman, M; Lartaud-Idjouadiene, I; Atkinson, J; Maincent, P

    1997-02-01

    1. The therapeutic use of nifedipine is limited by the rapidity of the onset of its action and its short biological half-life. In order to produce a form devoid of these disadvantages we made nanoparticles of nifedipine from three different polymers, poly-epsilon-caprolactone (PCL), polylactic and glycolic acid (1:1) copolymers (PLAGA), and Eudragit RL/RS (Eudragit). Nifedipine in polyethylene glycol 400 (PEG) solution was used as a control. 2. The average diameters of the nanoparticles ranged from 0.12 to 0.21 micron; the encapsulation ratio was 82% to 88%. 3. In spontaneously hypertensive rats (SHR), the initial rapid fall in systolic arterial blood pressure following oral administration of nifedipine in PEG solution (from 193 +/- 3 to 102 +/- 2 mmHg) was not seen following administration of the same dose in Eudragit nanoparticles (from 189 +/- 2 to 156 +/- 2 mmHg); with PCL and PLAGA nanoparticles the initial fall in blood pressure was significantly reduced (nadirs PCL 124 +/- 2 and PLAGA 113 +/- 2 mmHg). Ten hours following administration, blood pressure in rats administered the nifedipine/PEG preparation had returned to normal (183 +/- 3 mmHg) whereas that of animals given nifedipine in nanoparticles (PCL 170 +/- 3, PLAGA 168 +/- 2, Eudragit 160 +/- 3 mmHg) was still significantly reduced. 4. All of the nanoparticle dosage forms decreased Cmax and increased Tmax and the mean residence time (MRT) values. Relative bioavailability was significantly increased with Eudragit nanoparticles compared to the nifedipine/PEG solution. 5. There was an inverse linear correlation between the fall in blood pressure and plasma nifedipine concentration with all preparations. 6. The nanoparticle nifedipine preparations represent sustained release forms with increased bioavailability, a less pronounced initial antihypertensive effect and a long-lasting action.

  16. PHARMACOKINETICS OF DICLOFENAC SODIUM AND PAPAVERINE HYDROCHLORIDE AFTER ORAL ADMINISTRATION OF TABLETS TO RABBITS.

    Science.gov (United States)

    Kasperek, Regina; Zimmer, Łukasz; Jawień, Wojciech; Poleszak, Ewa

    2015-01-01

    Non-compartmental pharmacokinetic analysis of diclofenac sodium (DIC) and papaverine hydrochloride (PAP) after oral administration of composed tablets to rabbits was developed. HPLC method for determination of DIC and PAP in rabbit plasma was developed and validated. Chromatographic separation of DIC, PAP and the IS was achieved on a Zorbax SB C18 5-µm column (150 mm x 4.6 mm) using methanol-water (55:45, v/v) as mobile phase at a flow rate of 0.8 mL/min. Pharmacokinetic analysis showed that oral administration of a tablet composed of DIC and PAP do not change the pharmacokinetic parameters such as MRT, MAT, Cl and bioavailability of the active substances compared with single administration of DIC and PAP after single dose.

  17. Pharmacokinetics after oral and intravenous administration of a single dose of tramadol hydrochloride to Hispaniolan Amazon parrots (Amazona ventralis).

    Science.gov (United States)

    Souza, Marcy J; Sanchez-Migallon Guzman, David; Paul-Murphy, Joanne R; Cox, Sherry K

    2012-08-01

    To determine pharmacokinetics after IV and oral administration of a single dose of tramadol hydrochloride to Hispaniolan Amazon parrots (Amazona ventralis). 9 healthy adult Hispaniolan Amazon parrots (3 males, 5 females, and 1 of unknown sex). Tramadol (5 mg/kg, IV) was administered to the parrots. Blood samples were collected from -5 to 720 minutes after administration. After a 3-week washout period, tramadol (10 and 30 mg/kg) was orally administered to parrots. Blood samples were collected from -5 to 1,440 minutes after administration. Three formulations of oral suspension (crushed tablets in a commercially available suspension agent, crushed tablets in sterile water, and chemical-grade powder in sterile water) were evaluated. Plasma concentrations of tramadol and its major metabolites were measured via high-performance liquid chromatography. Mean plasma tramadol concentrations were > 100 ng/mL for approximately 2 to 4 hours after IV administration of tramadol. Plasma concentrations after oral administration of tramadol at a dose of 10 mg/kg were 100 ng/mL for approximately 6 hours after administration. Oral administration of the suspension consisting of the chemical-grade powder resulted in higher plasma tramadol concentrations than concentrations obtained after oral administration of the other 2 formulations; however, concentrations differed significantly only at 120 and 240 minutes after administration. Oral administration of tramadol at a dose of 30 mg/kg resulted in plasma concentrations (> 100 ng/mL) that have been associated with analgesia in Hispaniolan Amazon parrots.

  18. Thallium-201 myocardial imaging during pharmacologic coronary vasodilation: comparison of oral and intravenous administration of dipyridamole

    International Nuclear Information System (INIS)

    Taillefer, R.; Lette, J.; Phaneuf, D.C.; Leveille, J.; Lemire, F.; Essiambre, R.

    1986-01-01

    Although the diagnostic utility of thallium-201 myocardial imaging after dipyridamole infusion is well established, the intravenous form of the drug is not yet commercially available in North America. Fifty patients referred for coronary angiography were prospectively studied. Within a 2 week period, each patient underwent cardiac catheterization and thallium-201 myocardial imaging after both oral and intravenous dipyridamole administration. For the oral protocol, patients were randomly assigned to treatment with either 200 or 400 mg of dipyridamole in tablet form. Coronary artery stenoses of 70% or greater were considered significant. For the 25 patients who received a 200 mg oral dose of dipyridamole, the scintigraphic study showed perfusion defects in 65% of patients with significant coronary artery disease after the oral dose and in 85% of patients after the intravenous dose. For the 25 patients who received a 400 mg oral dose, the sensitivity of the scintigram was 84% after the oral dose and 79% after the intravenous dose. Except for headache and nausea, side effects were less severe and less frequent with oral (either 200 or 400 mg) than with intravenous dipyridamole. Because of the delayed and variable absorption of dipyridamole tablets, the oral studies required a longer period of medical supervision (45 to 60 minutes), and aminophylline was empirically administered after completion of the first set of thallium-201 images. It is concluded from this study that thallium-201 myocardial imaging after coronary vasodilation with a 400 mg oral dose of dipyridamole is a safe, widely available and reliable alternative for the evaluation of coronary artery disease in patients unable to achieve an adequate exercise level on stress testing

  19. Comparative study on the disposition of a new orally active dopamine prodrug, N-(N-acetyl-L-methionyl)-O,O-bis(ethoxycarbonyl)dopamine (TA-870) and dopamine hydrochloride in rats and dogs

    International Nuclear Information System (INIS)

    Yoshikawa, M.; Endo, H.; Otsuka, M.; Yamaguchi, I.; Harigaya, S.

    1988-01-01

    The pharmacokinetics of a dopamine derivative, TA-870, and dopamine (DA) after oral administration are compared in rats and dogs. The maximum concentrations of free DA in plasma after oral administration of TA-870 were 150 ng/ml in the rat (30 mg/kg) and 234 ng/ml in the dog (33.5 mg/kg). On the contrary, the maximum plasma concentrations after oral administration of DA at an equimolar dose to TA-870 were 12 ng/ml in the rat (12 mg/kg) and 36 ng/ml in the dog (13.5 mg/kg). The AUC values of free DA in plasma after oral administration of TA-870 (30 or 33.5 mg/kg) were 4-6 times higher than those after DA in both animal species. The peak tissue levels of radioactivity in rats after oral administration of [ 14 C]TA-870 (30 mg/kg) were also 5.5 times higher in the liver and 1-2 times higher in other tissues than those after [ 14 C]DA dose (12 mg/kg). In rats, the main excretion route of radioactivity after oral administration of [ 14 C]TA-870 or DA was via the urine. The total recoveries of radioactivity in the urine and feces were 91-96% of the dose within 24 hr for both compounds. Biliary excretion in rats accounted for 19.8% of the dose of [ 14 C]TA-870 and 12.6% of the dose of [ 14 C]DA within 24 hr. These results demonstrate that TA-870 was well absorbed from the digestive tract, extensively metabolized to dopamine, and proved to be an orally usable dopamine prodrug

  20. Effects of an oral insulin nanoparticle administration on hepatic glucose metabolism assessed by 13C and 2H isotopomer analysis

    NARCIS (Netherlands)

    Reis, C.P.; Neufeld, R.; Veiga, F.; Figueiredo, I.V.; Jones, J.; Soares, A.F.; Nunes, P.M.; Damg\\'e, C.; Carvalho, R.A.

    2012-01-01

    The purpose of this study was to evaluate hepatic glucose metabolism of diabetic induced rats after a daily oral load of insulin nanoparticles over 2 weeks. After the 2-week treatment, an oral glucose tolerance test was performed with [U-��C] glucose and �H2O. Plasma glucose �H and ��C enrichments

  1. 20 CFR 416.1448 - Deciding a case without an oral hearing before an administrative law judge.

    Science.gov (United States)

    2010-04-01

    ... § 416.1448 Deciding a case without an oral hearing before an administrative law judge. (a) Decision... the decision is based. (b) Parties do not wish to appear. (1) The administrative law judge may decide... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Deciding a case without an oral hearing...

  2. 20 CFR 404.948 - Deciding a case without an oral hearing before an administrative law judge.

    Science.gov (United States)

    2010-04-01

    ....948 Deciding a case without an oral hearing before an administrative law judge. (a) Decision wholly... is based. (b) Parties do not wish to appear. (1) The administrative law judge may decide a case on... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Deciding a case without an oral hearing...

  3. Relative oral bioavailability of 3-MCPD from 3-MCPD fatty acid esters in rats.

    Science.gov (United States)

    Abraham, Klaus; Appel, Klaus E; Berger-Preiss, Edith; Apel, Elisabeth; Gerling, Susanne; Mielke, Hans; Creutzenberg, Otto; Lampen, Alfonso

    2013-04-01

    In order to quantify the relative oral bioavailability of 3-chloropropane-1,2-diol (3-MCPD) from 3-MCPD fatty acid diesters in vivo, 1,2-dipalmitoyl-3-chloropropane-1,2-diol (3-MCPD diester) and 3-MCPD were orally applied to rats in equimolar doses. In both cases, the time courses of 3-MCPD concentrations were measured in blood, various organs, tissues and intestinal luminal contents. The results show that 3-MCPD is released by enzymatic hydrolysis from the 3-MCPD diester in the gastrointestinal tract and distributed to blood, organs and tissues. Based on the measurements in blood, the areas under the curve (AUC) for 3-MCPD were calculated. By comparing both AUC, the relative amount of 3-MCPD bioavailable from the 3-MCPD diester was calculated to be 86 % on average of the amount bioavailable following administration of 3-MCPD. In view of limited experimental data, it is justified for the purpose of risk assessment to assume complete hydrolysis of the diesters in the gastro-intestinal tract. Therefore, assessment of the extent of exposure to 3-MCPD released from its fatty acid esters should be performed in the same way as exposure to the same molar quantity of 3-MCPD.

  4. Conscious sedation by oral administration of midazolam in paediatric dental treatment.

    Science.gov (United States)

    Erlandsson, A L; Bäckman, B; Stenström, A; Stecksén-Blicks, C

    2001-01-01

    Midazolam is a short-acting benzodiazepine with rapid onset, short duration of action and minimal side effects. The aim of this study was to evaluate the oral administration of midazolam as pre-operative sedation in the dental treatment of uncooperative pediatric patients. Included in the study were 160 children with a mean age of 6.7 +/- 2.6 years (1-14 years), 83 boys and 77 girls. All the patients had been referred for specialist treatment due to behavioral management problems. Treatment was performed in 250 sessions. All the children received an oral dose of 0.2 mg/kg body weight of midazolam. Acceptance of treatment was evaluated according to Rud & Kisling. Local anesthesia followed by restorative treatment and/or extractions constituted more than 90% of the performed treatments. Of the 250 sessions, 63% were performed with total acceptance and 30% with doubtful acceptance. In 7%, no treatment could be performed. No serious complications were registered during or after treatment. All the children were able to leave the clinic one hour after treatment. In conclusion, we consider oral administration of midazolam a safe form of premedication. The route of administration, the short waiting-time and half-life, in combination with a level of sedation that allows treatment to be performed, are the principal advantages of conscious sedation with orally administered midazolam.

  5. Oral administration of a recombinant cholera toxin B subunit promotes mucosal healing in the colon.

    Science.gov (United States)

    Baldauf, K J; Royal, J M; Kouokam, J C; Haribabu, B; Jala, V R; Yaddanapudi, K; Hamorsky, K T; Dryden, G W; Matoba, N

    2017-07-01

    Cholera toxin B subunit (CTB) is a component of a licensed oral cholera vaccine. However, CTB has pleiotropic immunomodulatory effects whose impacts on the gut are not fully understood. Here, we found that oral administration in mice of a plant-made recombinant CTB (CTBp) significantly increased several immune cell populations in the colon lamina propria. Global gene expression analysis revealed that CTBp had more pronounced impacts on the colon than the small intestine, with significant activation of TGFβ-mediated pathways in the colon epithelium. The clinical relevance of CTBp-induced impacts on colonic mucosa was examined. In a human colon epithelial model using Caco2 cells, CTBp, but not the non-GM1-binding mutant G33D-CTBp, induced TGFβ-mediated wound healing. In a dextran sodium sulfate (DSS) acute colitis mouse model, oral administration of CTBp protected against colon mucosal damage as manifested by mitigated body weight loss, decreased histopathological scores, and blunted escalation of inflammatory cytokine levels while inducing wound healing-related genes. Furthermore, biweekly oral administration of CTBp significantly reduced disease severity and tumorigenesis in the azoxymethane/DSS model of ulcerative colitis and colon cancer. Altogether, these results demonstrate CTBp's ability to enhance mucosal healing in the colon, highlighting its potential application in ulcerative colitis therapy besides cholera vaccination.

  6. Protection from radiation injury through oral administration of PF4 gene carried by attenuated salmonella

    International Nuclear Information System (INIS)

    Zhao Lihua; Liu Bin; Yu Xiaofei; Zhang Lei; Han Zhongchao

    2005-01-01

    Objective: To investigate the in vivo radiation protection effect of PF4 by oral administration of attenuated salmonella as the carrier in mice. Methods: The eukaryotic vector pIRES2-EGFP-carried PF4 gene was transferred into an aroA-autotrophic mutant of salmonella typhimurium (SL3261), which was administered orally to BALBPc mice at 1x10 8 PFu once every interval three days. At 12 hours after the third oral administration the mice were subjected to a total body irradiation (TBI) of 700 cGy by a 60 Co source. The protective effect of SL3261/PF4 was determined by detection GFP ( green fluorescence protein) expression in tissues, peripheral blood count, culture of bone marrow colony-forming cells and survival time of mice. Results: Expression of GFP could be detected in the liver, spleen, intestine, kidney, peripheral blood and bone marrow. On days 7 and 14 after irradiation, Compared to controls, there were obvious differences in number of bone marrow mononuclear cells, CFU-GM (granulocyte-macrophage colony-forming unit ) and HPP-CFC (high proliferating potential-colony-forming cells) of mice treated with SL3261/PF4 (P<0.05) as well as prolongation of the survival time. Conclusion: These data demonstrate for the first time that PF4 protects mice from TBI injury and accelerates recovery of hematopoiesis by oral administration of attenuated salmonella carrying PF4 gene. (authors)

  7. DNA damage in rats after a single oral exposure to diesel exhaust particles

    DEFF Research Database (Denmark)

    Danielsen, Pernille Høgh; Risom, Lotte; Wallin, Håkan

    2008-01-01

    gavage of diesel exhaust particles (DEP) in terms of DNA damage, oxidative stress and DNA repair in colon epithelial cells, liver, and lung of rats. Eight rats per group were exposed to Standard Reference Material 2975 at 0.064 or 0.64 mg/kg bodyweight for 6 and 24 h. Increased levels of 8-oxo-7...... of DEP, but not in the colon and liver. A general response of the antioxidant defence system is further indicated by elevated levels of heme oxygenase 1 mRNA in the liver and lung 24 h after administration. The level of bulky DNA adducts was increased in liver and lung at both doses after 6 and 24h (DNA...... adducts in colon epithelium were not investigated). In summary, DEP administered via the gastrointestinal tract at low doses relative to ambient exposure generates DNA damage and increase the expression of defence mechanisms in organs such as the lung and liver. The oral exposure route should be taken...

  8. Transient renal impairment in rats after oral exposure to diethylene glycol.

    Science.gov (United States)

    Freundt, K J; Weis, N

    1989-10-01

    Volume, specific gravity, creatinine, lactate dehydrogenase (LDH), leucine aminopeptidase (LAP), beta-galactosidase (GAL), leucocytes, erythrocytes, nitrite, protein (albumin), glucose, ketone, urobilinogen, bilirubin and pH were estimated in urine of rats after single (by gavage) or repeated (via drinking water) oral administration of diethylene glycol (DEG). Following single or repetitive doses (daily over 90 days) of 0.2 g DEG kg-1 body weight, no change in renal function was observed (no effect level). In urine of rats treated once with 0.7 g DEG kg-1 body weight, LDH activity was significantly enhanced one day after treatment. A single dose of 2.0 g DEG kg-1 body weight resulted in an additional rise in urinary GAL activity two days after treatment, a significant rise of urinary volume and a decrease in creatinine concentration and pH on the first day. One day following a single dose of 8.0 g DEG kg-1 body weight, in addition to the changes mentioned before, LAP activity was significantly elevated and the specific gravity decreased. However, in all experiments the wet weight of the kidneys remained normal as compared to controls. The results thus show dose-dependent changes in several renal parameters, indicating a slight-to-moderate and reversible renal impairment.

  9. Malformations induced by gamma irradiation combined with vitamin A administration in pregnant female albino rats and their foetuses

    International Nuclear Information System (INIS)

    Ramadan, F.L.

    2007-01-01

    In The Present investigation, oral administration of vitamin A of the therapeutic doses and double therapeutic doses (9.000 lU/kg b.wt and 18.000 IU/ kg body, wt) to female rats starting on day 1 up to day 19 of pregnancy and exposed to 3 Gy (1 Gy/3 times) whole body gamma irradiation on days 7th, 1th and 15th of gestation (dissection was preformed on day 20) caused morphological, histochemical and skeletal changes in pregnant rats and their foetuses. The congenital anomalies occurred in foetuses when pregnant rats were exposed to γ-irradiation including diminution of size and subcutaneous haemorrhage. On the other hand, miscellaneous malformations including kypophysis, exencephally, anophthalmia and deformation of ear region were designated in foetuses maternally treated with excess vitamin A. The malformations were severe when mothers were irradiated during vitamin A administration as manifested by macrocephaly and fusion of digits of the hind limb (Oligosyndactyly). The examination of the endo skeletal system of foetuses obtained from irradiated pregnant rats and treated with low or excess doses of vitamin A showed retardation in of the ossification of the skull bones and lack of ossification at the centre of vertebrae. Moreover, no ossification was observed in sternebra, metacarpals, metatarsals and phalanges. In the present study, the content of DNA exhibited significant decrease in mother irradiated and combined or not with vitamin A. The results are of great importance from the standpoint of radiation protection and drug safety

  10. Efficacy and security of ivermectin given orally to rats naturally infected with Syphacia spp., Giardia spp. and Hymenolepis nana.

    Science.gov (United States)

    Foletto, V R S; Vanz, F; Gazarini, L; Stern, C A J; Tonussi, C R

    2015-07-01

    The results of this study show that the oral administration of ivermectin (48 mg/L) repeatedly for 72 h used in accordance with the present protocol is a safe and highly effective treatment for Giardia spp. and Hymenolepis nana in laboratory rat colonies. The drug can be easily and safely administered using drinking water. This simple regimen should control pinworm infection (Syphacia muris), a problem that can be endemic in laboratory colonies. Experiments using healthy animals are likely to generate more consistent results, thereby requiring a reduced number of animals per group. © The Author(s) 2014.

  11. Methylphenidate administration determines enduring changes in neuroglial network in rats.

    Science.gov (United States)

    Cavaliere, Carlo; Cirillo, Giovanni; Bianco, Maria Rosaria; Adriani, Walter; De Simone, Antonietta; Leo, Damiana; Perrone-Capano, Carla; Papa, Michele

    2012-01-01

    Repeated exposure to psychostimulant drugs induces complex molecular and structural modifications in discrete brain regions of the meso-cortico-limbic system. This structural remodeling is thought to underlie neurobehavioral adaptive responses. Administration to adolescent rats of methylphenidate (MPH), commonly used in attention deficit and hyperactivity disorder (ADHD), triggers alterations of reward-based behavior paralleled by persistent and plastic synaptic changes of neuronal and glial markers within key areas of the reward circuits. By immunohistochemistry, we observe a marked increase of glial fibrillary acidic protein (GFAP) and neuronal nitric oxide synthase (nNOS) expression and a down-regulation of glial glutamate transporter GLAST in dorso-lateral and ventro-medial striatum. Using electron microscopy, we find in the prefrontal cortex a significant reduction of the synaptic active zone length, paralleled by an increase of dendritic spines. We demonstrate that in limbic areas the MPH-induced reactive astrocytosis affects the glial glutamatergic uptake system that in turn could determine glutamate receptor sensitization. These processes could be sustained by NO production and synaptic rearrangement and contribute to MPH neuroglial induced rewiring. Copyright © 2011. Published by Elsevier B.V.

  12. Oral or parenteral administration of replication-deficient adenoviruses expressing the measles virus haemagglutinin and fusion proteins: protective immune responses in rodents.

    Science.gov (United States)

    Fooks, A R; Jeevarajah, D; Lee, J; Warnes, A; Niewiesk, S; ter Meulen, V; Stephenson, J R; Clegg, J C

    1998-05-01

    The genes encoding the measles virus (MV) haemagglutinin (H) and fusion (F) proteins were placed under the control of the human cytomegalovirus immediate early promoter in a replication-deficient adenovirus vector. Immunofluorescence and radioimmune precipitation demonstrated the synthesis of each protein and biological activity was confirmed by the detection of haemadsorption and fusion activities in infected cells. Oral as well as parenteral administration of the H-expressing recombinant adenovirus elicited a significant protective response in mice challenged with MV. While the F-expressing adenovirus failed to protect mice, cotton rats immunized with either the H- or F-expressing recombinant showed reduced MV replication in the lungs. Antibodies elicited in mice following immunization with either recombinant had no in vitro neutralizing activity, suggesting a protective mechanism involving a cell-mediated immune response. This study demonstrates the feasibility of using oral administration of adenovirus recombinants to induce protective responses to heterologous proteins.

  13. Time course effects of lithium administration on spatial memory acquisition and cholinergic marker expression in rats

    Directory of Open Access Journals (Sweden)

    M H Karimfar

    2009-08-01

    Full Text Available Background: The effects of chronic lithium exposure on spatial memory in rats remain controversial. In this study a time course of the effects of lithium, administered systemically, on spatial memory acquisition in Morris water maze was investigated. Material and Methods: Lithium (600 mg/L was administered to four groups of rats in their drinking water; the first group of animals received lithium for one week, the second group for two weeks, the third group for three weeks, and the fourth group for four weeks.  As controls, four groups of animals received only normal drinking water for the same period of time.  Toward the end of their lithium or water treatment, all animals were trained for four days; each day included one block and each block contained four trials.  Test trials were conducted 48 hrs after completion of the lithium treatment. Escape latency, traveled distance and swimming speed were evaluated during testing trials. Brain tissues from animals were processed according to the standard protocols for immunohistochemical analysis.  Results: Lithium treatment decreased escape latency and traveled distance, but not swimming speed, compared with controls, suggesting significant spatial memory acquisition enhancement by lithium. Quantitative analysis showed that lithium, particularly after four weeks of exposure, significantly increased the number and density of immunostained ChAT-containing (choline acetyltransferase neurons in the medial septal area in comparison with control groups.  There was also a significant correlation between the number of immunostained ChAT neurons and behavioral measures. Conclusion: These results suggest that chronic oral administration of lithium causes spatial memory acquisition improvement in rats and an increase in ChAT immunostaining levels in medial septal nuclei.

  14. Methodological Study to Develop Standard Operational Protocol on Oral Drug Administration for Children.

    Science.gov (United States)

    Bijarania, Sunil Kumar; Saini, Sushma Kumari; Verma, Sanjay; Kaur, Sukhwinder

    2017-05-01

    To develop standard operational protocol (SOP) on oral drug administration and checklist to assess the implementation of the developed SOP. In this prospective methodological study, SOPs were developed in five phases. In the first phase, the preliminary draft of SOPs and checklists were prepared based on literature review, assessment of current practices and focus group discussion (FGD) with bedside working nurses. In the second phase, content validity was checked with the help of Delphi technique (12 experts). Total four drafts were prepared in stages and necessary modifications were made as per suggestions after each Delphi round. Fourth Delphi round was performed after conducting a pilot study. In the fourth phase, all bedside nurses were trained as per SOPs and asked to practice accordingly and observation of thirty oral drug administrations in children was done to check reliability of checklists for implementation of SOPs. In Phase-V, 7 FGDs were conducted with bedside nurses to assess the effectiveness of SOPs. The Content Validity Index (CVI) of SOP and checklists was 99.77%. Overall standardized Cronbach's alpha was calculated as 0.94. All the nurses felt that the SOP is useful. Valid and feasible SOP for drug administration to children through oral route along with valid and reliable checklist were developed. It is recommended to use this document for drug administration to children.

  15. Pharmacokinetics of ketoprofen enantiomers following intravenous and oral administration to exercised Thoroughbred horses.

    Science.gov (United States)

    Knych, Heather K; Arthur, Rick M; Steinmetz, Stacy; McKemie, Dan S

    2016-01-01

    Ketoprofen (KTP) is currently only available as an injectable formulation for intravenous administration to horses. The primary goal of the study reported here was to characterize the pharmacokinetics of KTP, including determination of bioavailability following oral administration of the currently available injectable formulation as well as a paste formulation. KTP was administered intravenously and orally, and blood and urine samples were collected at various time points up to 96 h. KTP enantiomer concentrations were determined using LC–MS/MS, and pharmacokinetic analyses were performed. Mean ± standard error values for systemic clearance, steady state volume of distribution and terminal elimination half-life were 0.345 ± 0.033 [R(−) KTP] and 0.167 ± 0.016 [S(+) KTP] L/kg/h, 0.344 ± 0.044 [R(−) KTP] and 0.298 ± 0.025 [S(+) KTP] L/kg, and 2.49 ± 0.077 [R(−) KTP] and 2.86 ± 0.102 [S(+) KTP] h, respectively. Oral bioavailability was calculated as 69.5 ± 10.3% and 88.2 ± 15.9% for R(−) KTP and S(+) KTP, respectively, following administration of the injectable formulation and 53.0 ± 6.0 and 53.0 ± 16.0% for the R(−) KTP and S(+) KTP, respectively, following administration of KTP paste.

  16. Nonlinear pharmacokinetics of visnagin in rats after intravenous bolus administration.

    Science.gov (United States)

    Haug, Karin G; Weber, Benjamin; Hochhaus, Guenther; Butterweck, Veronika

    2012-01-23

    Ammi visnaga L. (syn. Khella, Apiaceae) preparations have traditionally been used in the Middle East for the treatment of kidney stone disease. Visnagin, a furanocoumarin derivative, is one of the main compounds of Ammi visnaga with potential effects on kidney stone prevention. To date, no information is available about the pharmacokinetic (PK) properties of visnagin. It was the aim of the study to characterize the PK properties of visnagin after intravenous (i.v.) bolus administration in rats and to develop an adequate model for the description of the observed data, including model parameter estimates. Therefore, three doses of visnagin (1.25, 2.5, and 5mg/kg) solubilized in 25% Captisol® were administered by i.v. bolus injection to male Sprague-Dawley rats. Plasma samples were extracted and subsequently analyzed using a validated LC-MS/MS method. Both non-compartmental and compartmental PK analyses were performed. A stepwise model building approach was applied including nonlinear mixed effect modeling for final model selection and to obtain final model estimates in NONMEM VI. The average areas under the curve (AUC(0-last)) after doses of 1.25, 2.5, and 5mg/kg were 1.03, 3.61, and 12.6 mg *h/l, respectively. The shape of the plasma concentration-time profiles and the observed disproportionate increase in AUC(0-last) with increasing dose suggested nonlinearity in the elimination of visnagin. A two-compartment Michaelis-Menten model provided the best fit with following typical values of the parameter estimates: 2.09 mg/(l*h) (V(max)), 0.08 mg/l (K(M)), 0.175 l (V(C)), 1.0 h⁻¹ (k₁₂), and 1.22 h⁻¹ (k₂₁). Associated inter-subject variability estimates (% CV) for V(max), K(M) and V(C) were 21.8, 70.9, and 9.2, respectively. Intra-subject variability (constant CV error model) was estimated to be 7.0%. The results suggest the involvement of a saturable process in the elimination of visnagin, possibly an enzyme or transporter system. Copyright © 2011

  17. [Pharmacokinetics of 8-O-acetylharpagide and harpagide after oral administration of Ajuga decumbens extract in beagle dog].

    Science.gov (United States)

    Wen, Bin-Yu; Li, Jian-Rong

    2013-06-01

    8-O-acetylharpagide and harpagide are two kinds of effective component of Ajuga decumbens extract. A sensitive LC-MS/MS method has been established for pharmacokinetics of 8-O-acetylharpagide and harpagide in beagle dog after oral administration of from A. decumbens extract. Female beagle dogs received orally 12.9, 25.7 mg x kg(-1) p. o. Concentrations of 8-O-acetylharpagide and harpagide in plasma were determined by LC-MS/MS method at different time points and all pharmacokinetic parameters were estimated by non-compartment analysis. The mobile phase consisted of 0.1% formic acid in water (A) and acetonitrile (B), which was run at a flow rate of 0.3 mL x min(-1). Chromatographic separation was achieved on an Agilent ZORBAX XDB-C18 column (2.1 mm x 50 mm, 3.5 microm) using a gradient elution of 5% B at 0-2 min, 95% B at 2. 1-5 min and 5% B at 5. 1-10 min. All analytes, including the IS, were monitored under positive ionization conditions and quantified in MRM mode with transitions of m/z 429.2-369.2 for 8-O-acetylharpagide, m/z 387.2-207.2 for harpagide, and m/z 149.2-103.1 for IS. High purity nitrogen was employed as both the nebulizing and drying gas. Other parameters of the mass spectrometer were optimized as follows: drying gas flow 10.0 L x min(-1); drying gas temperature 300 degrees C; capillary voltage 4 000 V. Results showed that 8-O-acetylharpagide and harpagide showed a dose-dependence profile. T(max) of 8-O-acetylharpagide is 1.7 h, and T(max) of harpagide is 1.57 h, which was higher than T(max) of 8-O-acetylharpagide and harpagide after oral administration of from A. decumbens extract in rats. The different pharmacokinetic parameters may be due to the species differences of rat and beagle dog.

  18. Pharmacokinetics of penciclovir after oral administration of its prodrug famciclovir to horses.

    Science.gov (United States)

    Tsujimura, Koji; Yamada, Masayuki; Nagata, Shun-ichi; Yamanaka, Takashi; Nemoto, Manabu; Kondo, Takashi; Kurosawa, Masahiko; Matsumura, Tomio

    2010-03-01

    We investigated the pharmacokinetics of penciclovir after oral administration of its prodrug famciclovir to horses. Following an oral dose of famciclovir at 20 mg/kg, maximum plasma concentrations of penciclovir occurred between 0.75 and 1.5 hr (mean 0.94 + or - 0.38 hr) after dosing and were in the range 2.22 to 3.56 microg/ml (mean 2.87 + or - 0.61 microg/ml). The concentrations of penciclovir declined in a biphasic manner after the peak concentration was attained. The mean half-life of the rapid elimination phase was 1.73 + or - 0.34 hr whereas that of the slow elimination phase was 34.34 + or - 13.93 hr. These pharmacokinetic profiles observed were similar to those of another antiherpesvirus drug, acyclovir, previously reported in horses following oral dosing of its prodrug valacyclovir.

  19. Neurobehavioral assessment of rats exposed to pristine polystyrene nanoplastics upon oral exposure.

    Science.gov (United States)

    Rafiee, Mohammad; Dargahi, Leila; Eslami, Akbar; Beirami, Elmira; Jahangiri-Rad, Mahsa; Sabour, Siamak; Amereh, Fatemeh

    2018-02-01

    The increasing use of plastics has raised concerns about pollution of freshwater by these polymeric materials. Knowledge about their potential effects on environmental and public health is limited. Recent publications have suggested that the degradation of plastics will result in the release of nano-sized plastic particles to the environment. Therefore, it is of utmost importance to gain knowledge about whether and how nanoplastics affect living organisms. The present study aimed to analyse potential neurobehavioral effects of polystyrene nanoparticles (PS-NPs) after long-term exposure on rat. Potential effects of PS-NPs were investigated using four test dosages (1, 3, 6, and 10 mg PS-NPs/kg of body weight/day) administrated orally with adult Wistar male rats for five weeks. Neurobehavioral tests were chosen to assess a variety of behavioral domains. Particle diameters in test suspensions were determined through dynamic light scattering and showed an average hydrodynamic diameter of approximately 38.92 nm. No statistically significant behavioral effects were observed in all tests performed (p > 0.05). In the elevated plus maze, PS-NPs-exposed rats showed greater number of entries into open arms compared to controls. Also, PS-NPs had no significant influence on body weight of animals. Taking into account the subtle and transient nature of neurobehavioral consequences, however, these results underline the possibility of even pristine plastic nanoparticles to induce behavioral alteration in the rest of the food web, including for marine biota and humans. Indeed even though studied neurobehavioral effects in our study was not statistically significant, the observed subtle effects may be clinically considerable. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Oral insulin improves metabolic parameters in high fat diet fed rats

    Directory of Open Access Journals (Sweden)

    LEANDRO C. LIPINSKI

    2017-08-01

    Full Text Available ABSTRACT Introduction/Aim: The gut has shown to have a pivotal role on the pathophysiology of metabolic disease. Food stimulation of distal intestinal segments promotes enterohormones secretion influencing insulin metabolism. In diabetic rats, oral insulin has potential to change intestinal epithelium behavior. This macromolecule promotes positive effects on laboratorial metabolic parameters and decreases diabetic intestinal hypertrophy. This study aims to test if oral insulin can influence metabolic parameters and intestinal weight in obese non-diabetic rats. Methods: Twelve weeks old Wistar rats were divided in 3 groups: control (CTRL standard chow group; high fat diet low carbohydrates group (HFD and HFD plus daily oral 20U insulin gavage (HFD+INS. Weight and food consumption were weekly obtained. After eight weeks, fasting blood samples were collected for laboratorial analysis. After euthanasia gut samples were isolated. Results: Rat oral insulin treatment decreased body weight gain (p<0,001, fasting glucose and triglycerides serum levels (p<0,05 an increased intestinal weight of distal ileum (P<0,05. Animal submitted to high fat diet presented higher levels of HOMA-IR although significant difference to CT was not achieved. HOMA-beta were significantly higher (p<0.05 in HFD+INS. Visceral fat was 10% lower in HFD+INS but the difference was not significant. Conclusions: In non-diabetic obese rats, oral insulin improves metabolic malfunction associated to rescue of beta-cell activity.

  1. Effect of repeated oral therapeutic doses of methylphenidate on food intake and growth rate in rats.

    Science.gov (United States)

    Alam, Nausheen; Najam, Rahila

    2015-01-01

    Central nervous system stimulants are known to produce anorexia. Previous data suggest that methylphenidate can have variable effects on caloric intake and growth rate. A dose-response study was performed to monitor caloric intake, liquid intake and growth rate in rats following repeated administration of human oral therapeutic doses 2 mg/kg/day, 5mg/kg/day and 8mg/kg/day of methylphenidate. We found that food intake and water intake, increased in all weeks and at all doses used in the study. Growth rate increased more at higher dose (8mg/kg/day) and at low dose (2mg/kg/day) of methylphenidate in 1(st) and 2(nd) week whereas more decreased by the above doses in 3(rd) week, suggesting that food stimulation leads to initial increase in growth rate but long term administration of methylphenidate attenuate growth rate that is not due to modulation of appetite but may be due to anxiety and increased activity produce by stimulants. A possible role of DA, 5HT receptors in modulation of appetite and anxiety is discussed.

  2. Detection of capecitabine (Xeloda®) on the skin surface after oral administration

    Science.gov (United States)

    Huang, Mao-Dong; Fuss, Harald; Lademann, Jürgen; Florek, Stefan; Patzelt, Alexa; Meinke, Martina C.; Jung, Sora

    2016-04-01

    Palmoplantar erythrodysesthesia (PPE), or hand-foot syndrome, is a cutaneous toxicity under various chemotherapeutics contributing to the most frequent side effects in patients treated with capecitabine (Xeloda®). The pathomechanism of PPE has been unclear. Here, the topical detection of capecitabine in the skin after oral application was shown in 10 patients receiving 2500 mg/m2/day capecitabine. Sweat samples were taken prior to and one week after oral administration of capecitabine. Using high-resolution continuum source absorption spectrometry, the changes in concentrations of fluorine, which is an ingredient of capecitabine, were quantified and statistically analyzed. Here, we show an increase in fluorine concentrations from 40±10 ppb (2±0.5 pM) before capecitabine administration to 27.7±11.8 ppm (14.6±6.5 nM) after application, ptoxic effect as a possible pathomechanism of PPE.

  3. Orally administered L-arginine and glycine are highly effective against acid reflux esophagitis in rats

    Science.gov (United States)

    Nagahama, Kenji; Nishio, Hikaru; Yamato, Masanori; Takeuchi, Koji

    2012-01-01

    Summary Background Reflux esophagitis is caused mainly by excessive exposure of the mucosa to gastric contents. In the present study, we examined the effect of several amino acids on acid reflux esophagitis in rats. Material/Methods After 18 h of fasting, acid reflux esophagitis was induced by ligating both the pylorus and the transitional region between the forestomach and the corpus under ether anesthesia, and the animals were killed 4 h later. The severity of esophagitis was reduced by the oral administration of omeprazole, a proton pump inhibitor, or pepstatin, a specific pepsin inhibitor. Results The development of esophageal lesions was dose-dependently prevented by L-arginine and glycine, given intragastrically (i.g.) after the ligation, with complete inhibition obtained at 250 mg/kg and 750 mg/kg, respectively, and these effects were not influenced by the prior s.c. administration of indomethacin or L-NAME. By contrast, both L-alanine and L-glutamine given i.g. after the ligation aggravated these lesions in a dose-dependent manner. These amino acids had no effect on acid secretion but increased the pH of the gastric contents to 1.8~2.3 due to their buffering action. Conclusions The results confirmed an essential role for acid and pepsin in the pathogenesis of acid reflux esophagitis in the rat model and further suggested that various amino acids affect the severity of esophagitis in different ways, due to yet unidentified mechanisms; L-alanine and L-glutamine exert a deleterious effect on the esophagitis, while L-arginine and glycine are highly protective, independent of endogenous prostaglandins and nitric oxide. PMID:22207112

  4. Oxycodone physical dependence and its oral self-administration in C57BL/6J mice.

    Science.gov (United States)

    Enga, Rachel M; Jackson, Asti; Damaj, M Imad; Beardsley, Patrick M

    2016-10-15

    Abuse of prescription opioids, such as oxycodone, has markedly increased in recent decades. While oxycodone's antinociceptive effects have been detailed in several preclinical reports, surprisingly few preclinical reports have elaborated its abuse-related effects. This is particularly surprising given that oxycodone has been in clinical use since 1917. In a novel oral operant self-administration procedure, C57BL/6J mice were trained to self-administer water before introducing increasing concentrations of oxycodone (0.056-1.0mg/ml) under post-prandial conditions during daily, 3-h test sessions. As the concentration of oxycodone increased, the numbers of deliveries first increased, then decreased in an inverted U-shape fashion characteristic of the patterns of other drugs self-administered during limited access conditions. After post-prandial conditions were removed, self-administration at the highest concentration was maintained suggesting oral oxycodone served as a positive reinforcer. In other mice, using a novel regimen of physical dependence, mice were administered increasing doses of oxycodone (9.0-33.0mg/kg, s.c.) over 9 days, challenged with naloxone (0.1-10.0mg/kg, s.c.), and then observed for 30min. Naloxone dose-dependently increased the observed number of somatic signs of withdrawal, suggesting physical dependence of oxycodone was induced under this regimen. This is the first report demonstrating induction of oral operant self-administration of oxycodone and dose-dependent precipitations of oxycodone withdrawal in C57BL/6J mice. The use of oral operant self-administration as well as the novel physical dependence regimen provides useful approaches to further examine the abuse- and dependence-related effects of this highly abused prescription opioid. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Promotion or suppression of experimental metastasis of B16 melanoma cells after oral administration of lapachol

    International Nuclear Information System (INIS)

    Maeda, Masayo; Murakami, Manabu; Takegami, Tsutomu; Ota, Takahide

    2008-01-01

    Lapachol [2-hydroxy-3-(3-methyl-2-butenyl)-1,4-naphthoquinone] is a vitamin K antagonist with antitumor activity. The effect of lapachol on the experimental metastasis of murine B16BL6 melanoma cells was examined. A single oral administration of a high toxic dose of lapachol (80-100 mg/kg) 6 h before iv injection of tumor cells drastically promoted metastasis. This promotion of metastasis was also observed in T-cell-deficient mice and NK-suppressed mice. In vitro treatment of B16BL6 cells with lapachol promoted metastasis only slightly, indicating that lapachol promotes metastasis primarily by affecting host factors other than T cells and NK cells. A single oral administration of warfarin, the most commonly used vitamin K antagonist, 6 h before iv injection of tumor cells also drastically promoted the metastasis of B16BL6 cells. The promotion of metastasis by lapachol and warfarin was almost completely suppressed by preadministration of vitamin K3, indicating that the promotion of metastasis by lapachol was derived from vitamin K antagonism. Six hours after oral administration of lapachol or warfarin, the protein C level was reduced maximally, without elongation of prothrombin time. These observations suggest that a high toxic dose of lapachol promotes metastasis by inducing a hypercoagulable state as a result of vitamin K-dependent pathway inhibition. On the other hand, serial oral administration of low non-toxic doses of lapachol (5-20 mg/kg) weakly but significantly suppressed metastasis by an unknown mechanism, suggesting the possible use of lapachol as an anti-metastatic agent

  6. Oxidatively damaged DNA in rats exposed by oral gavage to C60 fullerenes and single-walled carbon nanotubes

    DEFF Research Database (Denmark)

    Folkmann, Janne K; Risom, Lotte; Jacobsen, Nicklas R

    2009-01-01

    BACKGROUND: C60 fullerenes and single-walled carbon nanotubes (SWCNT) are projected to be used in medicine and consumer products with potential human exposure. The hazardous effects of these particles are expected to involve oxidative stress with generation of oxidatively damaged DNA that might...... be the initiating event in the development of cancer. OBJECTIVE: In this study we investigated the effect of a single oral administration of C60 fullerenes and SWCNT. METHODS: We measured the level of oxidative damage to DNA as the premutagenic 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) in the colon mucosa...... of genotoxicity, whereas corn oil per se generated more genotoxicity than the particles. Although there was increased mRNA expression of 8-oxoguanine DNA glycosylase in the liver of C60 fullerene-treated rats, we found no significant increase in repair activity. CONCLUSIONS: Oral exposure to low doses of C60...

  7. Pharmacokinetics of butorphanol after intravenous, intramuscular, and oral administration in Hispaniolan Amazon parrots (Amazona ventralis).

    Science.gov (United States)

    Guzman, David Sanchez-Migallon; Flammer, Keven; Paul-Murphy, Joanne R; Barker, Steven A; Tully, Thomas N

    2011-09-01

    Previous studies have validated the clinical use of opioids with kaap-receptor affinities for pain management in birds. Butorphanol, a kappa opioid receptor agonist and a mu opioid receptor antagonist, is currently considered by many clinicians to be the opioid of choice for this use. However, despite studies reporting the analgesic properties of butorphanol in psittacine birds, dosing intervals have not been established for any psittacine species. The goals of this study in the Hispaniolan Amazon parrot (Amazona ventralis) were to evaluate the pharmacokinetics of butorphanol tartrate after intravenous (IV), intramuscular (IM), and oral (PO) administration and to determine the bioavailability of butorphanol tartrate after oral administration. Twelve Hispaniolan Amazon parrots were used in the study, with a complete-crossover experimental design and a 3-month period separating each part of the study. The birds were randomly assigned to 3 groups (n = 4) for each stage. Butorphanol tartrate was administered once at a dose of 5 mg/kg in the basilic vein or pectoral muscles or as an oral solution delivered via feeding tube into the crop for the IV, IM, and PO studies, respectively. After butorphanol administration, blood samples were collected at 1, 5, 15, 30, 60, 90, 120, 180, and 240 minutes for the IV and IM studies and at 5, 15, 30, 60, 90, 120, 180, 240, and 300 minutes for the PO study. Because of the size limitation of the birds, naive pooling of datum points was used to generate a mean plasma butorphanol concentration at each time point. For each study, birds in each group (n = 4) were bled 3 times after dosing. Plasma butorphanol concentrations were determined by high-performance liquid chromatography/tandem mass spectrometry, and pharmacokinetic parameters were calculated. Butorphanol tartrate was found to have high bioavailability and rapid elimination following IM administration. In contrast, oral administration resulted in low bioavailability (Amazon

  8. Novel effects of a single administration of ferulic acid on the regulation of blood pressure and the hepatic lipid metabolic profile in stroke-prone spontaneously hypertensive rats.

    Science.gov (United States)

    Ardiansyah; Ohsaki, Yusuke; Shirakawa, Hitoshi; Koseki, Takuya; Komai, Michio

    2008-04-23

    We studied the effects of a single oral administration of ferulic acid (FA) on the blood pressure (BP) and lipid profile in stroke-prone spontaneously hypertensive rats (SHRSP). Male 12-week-old SHRSP were administered FA (9.5 mg/kg of body weight) and distilled water as the control (C) (1 mL) via a gastric tube. The hypotensive effect of FA was observed at the lowest value after 2 h administration. A decrease in the angiotensin-1-converting enzyme (ACE) activity in the plasma corresponded well with the reduction of BP. Plasma total cholesterol and triglyceride levels were lower after 2 h administration. The mRNA expression of genes involved in lipid and drug metabolism was downregulated in the FA group. These results suggest that oral administration of FA appears beneficial in improving hypertension and hyperlipidemia.

  9. Oral Administration of Recombinant Lactococcus lactis Expressing the Cellulase Gene Increases Digestibility of Fiber in Geese.

    Science.gov (United States)

    Zhou, Haizhu; Gao, Yunhang; Gao, Guang; Lou, Yujie

    2015-12-01

    Enhancing cellulose digestibility in animals is important for improving the utilization of forage, which can decrease the amount of food used in animal production. The aim of the present study was to achieve recombinant expression of the cellulase gene in Lactococcus lactis and evaluate the effects of oral administration of the recombinant L. lactis on fiber digestibility in geese. Cellulase (Cell) and green fluorescent protein (GFP) genes were cloned into a L. lactis expression vector (pNZ8149) to construct the recombinant expression plasmid (pNZ8149-GFP-Cell). Then, the recombinant expression plasmid was transformed into L. lactis (NZ3900) competent cells by electroporation to obtain recombinant L. lactis (pNZ8149-GFP-Cell/NZ3900) in which protein expression was induced by Nisin. Expression of GFP and Cell by the recombinant L. lactis was confirmed using SDS-PAGE, fluorescence detection, and Congo red assays. A feeding experiment showed that oral administration of pNZ8149-GFP-Cell/NZ3900 significantly increased the digestibility of dietary fiber in geese fed either a maize stalk diet or a rice chaff diet. Therefore, oral administration of recombinant L. lactis cells expressing the cellulase gene increases fiber digestibility in geese, offering a way to increase the utilization of dietary fiber in geese.

  10. Pharmacokinetics of [3H]levamisole in pigs after oral and intramuscular administration

    International Nuclear Information System (INIS)

    Galtier, P.; Escoula, L.; Alvinerie, M.

    1983-01-01

    A single oral (10 mg/kg of body weight) or IM (7.5 mg/kg) dose of [ 3 H]levamisole was administered to pigs. Liquid scintillation counting and high performance liquid chromatography were used to determine total radioactivity and drug levels in plasma, duodenal and cecal contents, bile, and urine for 24 and 72 hours after dosing. Pharmacokinetic analysis indicated a 1-compartment open model with higher plasma bioavailability of levamisole after IM injection. Biological half-lives for elimination of the drug were 9.3 and 6.9 hours after oral and IM administration, respectively. Anthelmintic concentrations were higher in intestinal contents after oral gavage than after IM injection. The drug appeared extensively metabolized in all body fluids and particularly in bile, regardless of the route of administration. Biliary excretion of radioactivity and unchanged levamisole represented only slight percentages of the administered dose (approx 0.4% and 4.2%, respectively, in 72 hours). In contrast, about 60% and 20% of the dose were eliminated via urine as tritiated materials and unchanged drug. The choice of the most efficacious route of administration is discussed in regard to localization of helminthic disease

  11. Pharmacokinetics of (/sup 3/H)levamisole in pigs after oral and intramuscular administration

    Energy Technology Data Exchange (ETDEWEB)

    Galtier, P.; Escoula, L.; Alvinerie, M.

    1983-04-01

    A single oral (10 mg/kg of body weight) or IM (7.5 mg/kg) dose of (/sup 3/H)levamisole was administered to pigs. Liquid scintillation counting and high performance liquid chromatography were used to determine total radioactivity and drug levels in plasma, duodenal and cecal contents, bile, and urine for 24 and 72 hours after dosing. Pharmacokinetic analysis indicated a 1-compartment open model with higher plasma bioavailability of levamisole after IM injection. Biological half-lives for elimination of the drug were 9.3 and 6.9 hours after oral and IM administration, respectively. Anthelmintic concentrations were higher in intestinal contents after oral gavage than after IM injection. The drug appeared extensively metabolized in all body fluids and particularly in bile, regardless of the route of administration. Biliary excretion of radioactivity and unchanged levamisole represented only slight percentages of the administered dose (approx 0.4% and 4.2%, respectively, in 72 hours). In contrast, about 60% and 20% of the dose were eliminated via urine as tritiated materials and unchanged drug. The choice of the most efficacious route of administration is discussed in regard to localization of helminthic disease.

  12. Protective effect of oral administration of transgenic tobacco seeds against verocytotoxic Escherichia coli strain in piglets.

    Science.gov (United States)

    Rossi, Luciana; Dell'Orto, Vittorio; Vagni, Simona; Sala, Vittorio; Reggi, Serena; Baldi, Antonella

    2014-03-01

    The use of transgenic plants as delivery system for antigenic proteins is attractive for its simplicity and increases likelihood for local immune response at sites of infection. The aim of this study was to evaluate the protective effect of oral administration of tobacco seeds, expressing the FedA, the major protein of the F18 adhesive fimbriae, and B subunit of verocytotoxin, against verocytotoxin-producing E. coli (VTEC) strain in piglets. Forty-three early weaned piglets, were randomly divided into 4 experimental groups: 3 test groups and a control. Treatment groups orally received a bolus, with different dose of tobacco seeds on 0, 1, 2, 14 days post primary administration. After challenge, with 1*10(10) CFU of O138 Escherichia coli strain, piglets showed clinical scores significantly higher in the control group compared to orally immunized groups (P administration of recombinant tobacco seeds expressing antigenic proteins against VTEC strains can induce a protective effect against challenger strain in piglets.

  13. Combined Administration of Taurine and Monoisoamyl Dmsa Protects Arsenic Induced Oxidative Injury in Rats

    Directory of Open Access Journals (Sweden)

    Swaran J. S. Flora

    2008-01-01

    Full Text Available Arsenic is a naturally occurring element that is ubiquitously present in the environment. High concentration of naturally occurring arsenic in drinking water is a major health problem in different parts of the world. Despite arsenic being a health hazard and a well documented carcinogen, no safe, effective and specific preventive or therapeutic measures are available. Among various recent strategies adopted, administration of an antioxidant has been reported to be the most effective. The present study was designed to evaluate the therapeutic efficacy of monoisoamyl dimercaptosuccinic acid (MiADMSA, administered either individually or in combination with taurine post chronic arsenic exposure in rats. Arsenic exposed male rats (25 ppm, sodium arsenite in drinking water for 24 weeks were treated with taurine (100 mg/kg, i.p., once daily, monoisoamyl dimercaptosuccinic acid (MiADMSA (50 mg/kg, oral, once daily either individually or in combination for 5 consecutive days. Biochemical variables indicative of oxidative stress along-with arsenic concentration in blood, liver and kidney were measured. Arsenic exposure significantly reduced blood δ-aminolevulinic acid dehydratase (ALAD activity, a key enzyme involved in the heme biosynthesis and enhanced zinc protoporphyrin (ZPP level. Clinical hematological variables like white blood cells (WBC, mean cell hemoglobin (MCH, and mean cell hemoglobin concentration (MCHC showed significant decrease with a significant elevation in platelet (PLT count. These changes were accompanied by significant decrease in superoxide dismutase (SOD activity and increased catalase activity. Arsenic exposure caused a significant decrease in hepatic and renal glutathione (GSH level and an increase in oxidized glutathione (GSSG. These biochemical changes were correlated with an increased uptake of arsenic in blood, liver and kidney. Administration of taurine significantly reduced hepatic oxidative stress however co-administration

  14. Solid-state dependent dissolution and oral bioavailability of piroxicam in rats.

    Science.gov (United States)

    Lust, Andres; Laidmäe, Ivo; Palo, Mirja; Meos, Andres; Aaltonen, Jaakko; Veski, Peep; Heinämäki, Jyrki; Kogermann, Karin

    2013-01-23

    The aim of this study was to gain understanding about the effects of different solid-state forms of a poorly water-soluble piroxicam on drug dissolution and oral bioavailability in rats. Three different solid-state forms of piroxicam were studied: anhydrate I (AH), monohydrate (MH), and amorphous form in solid dispersion (SD). In addition, the effect of a new polymeric excipient Soluplus® (polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer) on oral bioavailability of piroxicam was investigated. Significant differences in the dissolution and oral bioavailability were found between the solid-state forms of piroxicam. Amorphous piroxicam in SD showed the fastest dissolution in vitro and a solid-state transformation to MH in the dissolution medium. Despite the presence of solid-state transformation, SD exhibited the highest rate and extent of oral absorption in rats. Oral bioavailability of other two solid-state forms decreased in the order AH and MH. The use of Soluplus® was found to enhance the dissolution and oral bioavailability of piroxicam in rats. The present study shows the importance of solid-state form selection for oral bioavailability of a poorly water-soluble drug. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Sex-dependent response of some rat biochemical, histological and embryological features to Squalene administration or/ and gamma radiation exposure

    International Nuclear Information System (INIS)

    Ibrahim, M.F.; Abo-Zid, N.M.; Ahmed, A.G.

    2012-01-01

    Squalene, an intermediate of cholesterol biosynthesis, is known to possess potent antioxidant properties. The objective of the current study was to evaluate the influence of Squalene on some radiation-induced biochemical, histological and embryological changes in Sprague Dawley rats. Squalene was orally administered to rats (5 ml/kg/day) throughout 60 days before whole body gamma irradiation with 4 Gy. In adult male and female rats, the results revealed that Squalene has modulated the radiation produced abrupt elevation of total cholesterol (TC), triglycerides (TG) and and low density lipoprotein-cholesterol (LDL-C) levels and reduction of high density lipoprotein-cholesterol (HDL-C) ones in both male and female serum and male liver samples whereas it could not control the abrupt increase of HDL-C and decline of LDL-C in female liver values. Also Squalene has modified the histopathological acquired radiation lesions of both male and female colonic and hepatic tissues yet the female tested colonic sections showed moderate regeneration of crypts and villi layers whereas the hepatic sections yet displayed apparent hemorrhage and fatty liver infiltration of inflammatory cells. However, in the mated male rats and their pregnant counterparts, Squalene considerably restored the radiation induced male and female sex hormonal abrupt changes especially in female rats. Squalene administration to pergnant rats before irradiation at gestational day 17 improved the fetal survival ability as identified by the disappearance of resorption sites in the tested maternal uteri. Hence, it could be concluded that Squalene radioprotective capability surpassed the adult male rats than the female ones though it specified the pregnant females by protecting their growing embryos against radiation induced intrauterine fatal effect

  16. Development and evaluation of polymer nanoparticles for oral delivery of estradiol to rat brain in a model of Alzheimer's pathology.

    Science.gov (United States)

    Mittal, G; Carswell, H; Brett, R; Currie, S; Kumar, M N V Ravi

    2011-03-10

    The purpose of this study was to develop tween 80 (T-80) coated polylactide-co-glycolide (PLGA) nanoparticles that can deliver estradiol to the brain upon oral administration. Estradiol containing nanoparticles were made by a single emulsion technique and T-80 coating was achieved by incubating the re-constituted nanoparticles at different concentrations of T-80. The process of T-80 coating on the nanoparticles was optimized and the pharmacokinetics of estradiol nanoparticles was studied as a function of T-80 coating. The nanoparticles were then evaluated in an ovariectomized (OVX) rat model of Alzheimer's disease (AD) that mimics the postmenopausal conditions. The nanoparticles bound T-80 were found to proportionally increase from 9.72 ± 1.07 mg to 63.84 ± 3.59 mg with an increase in the initial concentration T-80 from 1% to 5% and were stable in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). Orally administered T-80 coated nanoparticles resulted in significantly higher brain estradiol levels after 24h (1.969 ± 0.197 ng/g tissue) as compared to uncoated ones (1.105 ± 0.136 ng/g tissue) at a dose of 0.2mg/rat, suggesting a significant role of surface coating. Moreover, these brain estradiol levels were almost similar to those obtained after administration of the same dose of drug suspension via 100% bioavailable intramuscular route (2.123 ± 0.370 ng/g tissue), indicating the increased fraction of bioavailable drug reaching the brain when administered orally. Also, the nanoparticle treated group was successful in preventing the expression of amyloid beta-42 (Aβ42) immunoreactivity in the hippocampus region of brain. Together, the results indicate the potential of nanoparticles for oral delivery of estradiol to brain. Copyright © 2010 Elsevier B.V. All rights reserved.

  17. Histopathologic Study Following Administration of Liposome-Encapsulated Hemoglobin in the Normovolemic Rat

    National Research Council Canada - National Science Library

    Rudolph, Alan

    1995-01-01

    ... bovine hemoglobin in the normovolemic rat. We have also examined the administration of the liposome vehicle, tetrameric bovine hemoglobin, and liposome encapsulated bovine hemoglobin that had been lyophilized with 300 mM trehalose...

  18. Antinociceptive effects after oral administration of tramadol hydrochloride in Hispaniolan Amazon parrots (Amazona ventralis).

    Science.gov (United States)

    Sanchez-Migallon Guzman, David; Souza, Marcy J; Braun, Jana M; Cox, Sherry K; Keuler, Nicholas S; Paul-Murphy, Joanne R

    2012-08-01

    To evaluate antinociceptive effects on thermal thresholds after oral administration of tramadol hydrochloride to Hispaniolan Amazon parrots (Amazona ventralis). Animals-15 healthy adult Hispaniolan Amazon parrots. 2 crossover experiments were conducted. In the first experiment, 15 parrots received 3 treatments (tramadol at 2 doses [10 and 20 mg/kg] and a control suspension) administered orally. In the second experiment, 11 parrots received 2 treatments (tramadol hydrochloride [30 mg/kg] and a control suspension) administered orally. Baseline thermal foot withdrawal threshold was measured 1 hour before drug or control suspension administration; thermal foot withdrawal threshold was measured after administration at 0.5, 1.5, 3, and 6 hours (both experiments) and also at 9 hours (second experiment only). For the first experiment, there were no overall effects of treatment, hour, period, or any interactions. For the second experiment, there was an overall effect of treatment, with a significant difference between tramadol hydrochloride and control suspension (mean change from baseline, 2.00° and -0.09°C, respectively). There also was a significant change from baseline for tramadol hydrochloride at 0.5, 1.5, and 6 hours after administration but not at 3 or 9 hours after administration. Tramadol at a dose of 30 mg/kg, PO, induced thermal antinociception in Hispaniolan Amazon parrots. This dose was necessary for induction of significant and sustained analgesic effects, with duration of action up to 6 hours. Further studies with other types of noxious stimulation, dosages, and intervals are needed to fully evaluate the analgesic effects of tramadol hydrochloride in psittacines.

  19. Pharmacokinetics of meloxicam after intravenous, intramuscular, and oral administration of a single dose to Hispaniolan Amazon parrots (Amazona ventralis).

    Science.gov (United States)

    Molter, Christine M; Court, Michael H; Cole, Gretchen A; Gagnon, David J; Hazarika, Suwagmani; Paul-Murphy, Joanne R

    2013-03-01

    To compare pharmacokinetics after IV, IM, and oral administration of a single dose of meloxicam to Hispaniolan Amazon parrots (Amazona ventralis). 11 healthy parrots. Cohorts of 8 of the 11 birds comprised 3 experimental groups for a crossover study. Pharmacokinetics were determined from plasma concentrations measured via high-performance liquid chromatography after IV, IM, and oral administration of meloxicam at a dose of 1 mg/kg. Initial mean ± SD plasma concentration of 17.3 ± 9.0 μg/mL was measured 5 minutes after IV administration, whereas peak mean concentration was 9.3 ± 1.8 μg/mL 15 minutes after IM administration. At 12 hours after administration, mean plasma concentrations for IV (3.7 ± 2.5 μg/mL) and IM (3.5 ± 2.2 μg/mL) administration were similar. Peak mean plasma concentration (3.5 ± 1.2 μg/mL) was detected 6 hours after oral administration. Absolute systemic bioavailability of meloxicam after IM administration was 100% but was lower after oral administration (range, 49% to 75%). Elimination half-lives after IV, IM, and oral administration were similar (15.9 ± 4.4 hours, 15.1 ± 7.7 hours, and 15.8 ± 8.6 hours, respectively). Pharmacokinetic data may provide useful information for use of meloxicam in Hispaniolan Amazon parrots. A mean plasma concentration of 3.5 μg/mL would be expected to provide analgesia in Hispaniolan Amazon parrots; however, individual variation may result in some birds having low plasma meloxicam concentrations after IV, IM, or oral administration. After oral administration, meloxicam concentration slowly reached the target plasma concentration, but that concentration was not sustained in most birds.

  20. Boron microquantification in oral mucosa and skin following administration of a neutron capture therapy agent

    International Nuclear Information System (INIS)

    Kiger, S.W. III; Micca, P.L.; Morris, G.M.; Coderre, J.A.

    2002-01-01

    Clinical trials of boron neutron capture therapy (BNCT) for intracranial tumours using boronphenylalanine-fructose undertaken at Harvard-MIT and Brookhaven National Laboratory have observed acute normal tissue reactions in the skin and oral mucosa. Because the range of the 10 B(n,a) 7 Li reaction products is very short, 10-14 μm combined, knowledge of the 10B microdistribution in tissue is critical for understanding the microdosimetry and radiobiology of BNCT. This paper reports measurements of the microdistribution of 10 B in an animal model, rat skin and tongue, using high resolution quantitative autoradiography (HRQAR), a neutron-induced track etch autoradiographic technique. The steep spatial gradient and high absolute value relative to blood of the 10 B concentration observed in some strata of the rat tongue epithelium and skin are important for properly evaluating the radiobiology and the biological effectiveness factors for normal tissue reactions such as oral mucositis, which are generally assessed using the blood boron concentration rather than the tissue boron concentration. (author)

  1. Pharmacokinetics of meloxicam in koalas (Phascolarctos cinereus) after intravenous, subcutaneous and oral administration.

    Science.gov (United States)

    Kimble, B; Black, L A; Li, K M; Valtchev, P; Gilchrist, S; Gillett, A; Higgins, D P; Krockenberger, M B; Govendir, M

    2013-10-01

    The pharmacokinetic profile of meloxicam in clinically healthy koalas (n = 15) was investigated. Single doses of meloxicam were administered intravenously (i.v.) (0.4 mg/kg; n = 5), subcutaneously (s.c.) (0.2 mg/kg; n = 1) or orally (0.2 mg/kg; n = 3), and multiple doses were administered to two groups of koalas via the oral or s.c. routes (n = 3 for both routes) with a loading dose of 0.2 mg/kg for day 1 followed by 0.1 mg/kg s.i.d for a further 3 days. Plasma meloxicam concentrations were quantified by high-performance liquid chromatography. Following i.v. administration, meloxicam exhibited a rapid clearance (CL) of 0.44 ± 0.20 (SD) L/h/kg, a volume of distribution at terminal phase (Vz ) of 0.72 ± 0.22 L/kg and a volume of distribution at steady state (Vss ) of 0.22 ± 0.12 L/kg. Median plasma terminal half-life (t(1/2)) was 1.19 h (range 0.71-1.62 h). Following oral administration either from single or repeated doses, only maximum peak plasma concentration (C(max) 0.013 ± 0.001 and 0.014 ± 0.001 μg/mL, respectively) was measurable [limit of quantitation (LOQ) >0.01 μg/mL] between 4-8 h. Oral bioavailability was negligible in koalas. Plasma protein binding of meloxicam was ~98%. Three meloxicam metabolites were detected in plasma with one identified as the 5-hydroxy methyl derivative. This study demonstrated that koalas exhibited rapid CL and extremely poor oral bioavailability compared with other eutherian species. Accordingly, the currently recommended dose regimen of meloxicam for this species appears inadequate. © 2013 John Wiley & Sons Ltd.

  2. Recent mouse and rat methods for the study of experimental oral candidiasis.

    Science.gov (United States)

    Costa, Anna C B P; Pereira, Cristiane A; Junqueira, Juliana C; Jorge, Antonio O C

    2013-07-01

    The Candida genus expresses virulence factors that, when combined with immunosuppression and other risk factors, can cause different manifestations of oral candidiasis. The treatment of mucosal infections caused by Candida and the elucidation of the disease process have proven challenging. Therefore, the study of experimentally induced oral candidiasis in rats and mice is useful to clarify the etiopathology of this condition, improve diagnosis, and search for new therapeutic options because the disease process in these animals is similar to that of human candidiasis lesions. Here, we describe and discuss new studies involving rat and mouse models of oral candidiasis with respect to methods for inducing experimental infection, methods for evaluating the development of experimental candidiasis, and new treatment strategies for oral candidiasis.

  3. Recent mouse and rat methods for the study of experimental oral candidiasis

    Science.gov (United States)

    Costa, Anna CBP; Pereira, Cristiane A; Junqueira, Juliana C; Jorge, Antonio OC

    2013-01-01

    The Candida genus expresses virulence factors that, when combined with immunosuppression and other risk factors, can cause different manifestations of oral candidiasis. The treatment of mucosal infections caused by Candida and the elucidation of the disease process have proven challenging. Therefore, the study of experimentally induced oral candidiasis in rats and mice is useful to clarify the etiopathology of this condition, improve diagnosis, and search for new therapeutic options because the disease process in these animals is similar to that of human candidiasis lesions. Here, we describe and discuss new studies involving rat and mouse models of oral candidiasis with respect to methods for inducing experimental infection, methods for evaluating the development of experimental candidiasis, and new treatment strategies for oral candidiasis. PMID:23715031

  4. Studies on the absorption of iron after oral administration in piglets

    International Nuclear Information System (INIS)

    Thoren-Tolling, K.

    1975-01-01

    72 newborn piglets from 9 litters were used to determinate the retention and distribution in the body of labelled iron given either orally as ferrous fumarate (100 mg Fe 2+ ) or iron dextran (200 mg Fe 3+ ), or by injection as iron dextran (100 mg Fe 3+ ). About 25-30 % of the radioiron from a single oral dose of labelled ferrous fumarate (100 mg Fe 2+ ), and about 55-60 % from a single oral dose of labelled iron dextran (200 mg Fe 3+ ) were absorbed by the body. As iron is excreted throughout the experiment, only about 20% and 40-50% respectively of the radio-iron from these iron compounds were recovered 3 weeks after treatment. The total amounts of labelled iron retained in the body after oral administration of the same doses of these iron compounds, alone or in combination, were compared. A slight retardation of the absorption of ferrous iron was observed when iron dextran was administered simultaneeously. The absorption of iron dextran was not influenced by the simultaneous administration of ferrous fumarate. The importance of the liver as the main iron storage site was shown, and the rapid utilization of iron from storage sites, about 2-3 weeks after treatment was demonstrated. The concentration of labelled iron in urine and some lymphglands was measured. Only minute quantities of radio-iron were excreted in the urine throughout the entire experiment. The lymph nodes seem to act as iron stones after administration of iron dextran. The importance of the lymphatic tissue in absorption and storage of labelled iron is discussed. (author)

  5. Pharmacokinetics of dexmedetomidine combined with methadone following oral-transmucosal and intramuscular administration in dogs

    Directory of Open Access Journals (Sweden)

    Federica Di Cesare

    2017-05-01

    Full Text Available Oral-transmucosal (OTM drug delivery refers to noninvasive and painless administration of medical preparations through any oral cavity membrane to achieve systemic effects (Sattar et al., 2014. Regarding sedative drugs, OTM administration is very attractive in veterinary medicine, especially for patients difficult to inject and restrain (Messenger et al., 2016. This study aims to compare the pharmacokinetics of dexmedetomidine after OTM and intramuscular (IM administration combined with methadone. After obtaining Ethical Committee approval and owner’s written consent, eight dogs, were administered with dexmedetomidine (10 mg/kg and methadone (0.4 mg/kg by OTM and other 4 dogs by IM route. Blood samples were collected at prefixed times up to four hours. Dexmedetomidine was quantified by a validated HPLC-MS method. On dexmedetomidine concentrations, a pharmacokinetic analysis was carried out with a noncompartmental approach (Phoenix WinNonlin® 7.0, Pharsight, Cary, NC. Mean ± SD terminal half-lives of dexmedetomidine were 187.42 ± 109.66 and 94.78 ± 34.08 min after OTM and IM administration, respectively. Maximum serum (Cmax concentrations were 0.83 ± 0.32 and 9.09 ± 2.46 ng/mL for OTM and IM administration, respectively. Time to maximum concentration (Tmax were 44.38 ± 32.16 and 21.25±11.39 min by OTM and IM administration, respectively. Area under the curve from 0 to the last measured concentration (AUClast were 103.75 ± 30.23 and 614.87 ± 77.15 min*ng/mL for OTM and IM administration, respectively. Cmax, Tmax and AUClast values by OTM route demonstrate a lower and delayed absorption of the drug compared to IM. To complete the study, the pharmacokinetic analysis of methadone is foreseen, so as a clinical trial to compare the clinical effects of the combination of dexmedetomidine and methadone by OTM and IM administration and to establish an effective dosage of oral-transumucosal route in dogs for this association.

  6. Prevention of Infectious Mastitis by Oral Administration of Lactobacillus salivarius PS2 During Late Pregnancy.

    Science.gov (United States)

    Fernández, Leónides; Cárdenas, Nivia; Arroyo, Rebeca; Manzano, Susana; Jiménez, Esther; Martín, Virginia; Rodríguez, Juan Miguel

    2016-03-01

    Previous studies have shown that oral administration of lactobacilli can be an efficient approach to treat lactational infectious mastitis. In this trial, we have evaluated the potential of Lactobacillus salivarius PS2 to prevent this condition when orally administered during late pregnancy to women who had experienced infectious mastitis after previous pregnancies. In this study, 108 pregnant women were randomly assigned to one of 2 groups. Those in the probiotic group (n = 55) ingested daily 9 log10 colony-forming units of L. salivarius PS2 from approximately week 30 of pregnancy until delivery, whereas those in the placebo group (n = 53) received a placebo. The occurrence of mastitis was evaluated during the first 3 months after delivery. Globally, 44 of 108 women (41%) developed mastitis; however, the percentage of women with mastitis in the probiotic group (25% [n = 14]) was significantly lower than in the control group (57% [n = 30]). When mastitis occurred, the milk bacterial counts in the probiotic group were significantly lower than those obtained in the placebo group. Oral administration of L. salivarius PS2 during late pregnancy appears to be an efficient method to prevent infectious mastitis in a susceptible population. NCT01505361. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  7. Pharmacokinetics of enrofloxacin following oral and subcutaneous administration in the common ringtail possum (Pseudocheirus peregrinus).

    Science.gov (United States)

    Scheelings, T F; Devi, J L; Woodward, A P; Whittem, T

    2015-10-01

    [Correction added on 23 March 2015, after first online publication: Terminal half-life values of enrofloxacin is corrected in the fourth sentence of the abstract] Clinically healthy common ringtail possums (n = 5) received single doses of 10 mg/kg enrofloxacin orally and then 2 weeks later subcutaneously. Serial plasma samples were collected over 24 h for each treatment phase, and enrofloxacin concentrations were determined using a validated HPLC assay. Pharmacokinetic parameters were determined by noncompartmental analysis. Following oral administration, plasma concentrations were of therapeutic relevance (Cmax median 5.45 μg/mL, range 2.98-6.9 μg/mL), with terminal-phase half-life (t½ ) shorter than in other species (median 3.09 h, range 1.79-5.30 h). In contrast, subcutaneous administration of enrofloxacin did not achieve effective plasma concentrations, with plasma concentrations too erratic to fit the noncompartmental model except in one animal. On the basis of the AUC:MIC, enrofloxacin administered at 10 mg/kg orally, but not subcutaneously, is likely to be effective against a range of bacterial species that have been reported in common ringtail possums. © 2015 John Wiley & Sons Ltd.

  8. Renal, gastrointestinal, and hemostatic effects of oral administration of meloxicam to Hispaniolan Amazon parrots (Amazona ventralis).

    Science.gov (United States)

    Dijkstra, Bas; Guzman, David Sanchez-Migallon; Gustavsen, Kate; Owens, Sean D; Hass, Carlyle; Kass, Philip H; Paul-Murphy, Joanne R

    2015-04-01

    To investigate renal, gastrointestinal, and hemostatic effects associated with oral administration of multiple doses of meloxicam to healthy Hispaniolan Amazon parrots (Amazona ventralis). 12 Hispaniolan Amazon parrots. Birds were assigned to receive meloxicam oral suspension (1.6 mg/kg, PO, q 12 h) and 2.5 mL of tap water inserted into the crop by use of a gavage tube (n = 8) or the equivalent volume of tap water only (control group; 4) for 15 days. Urine and feces were collected 2 hours after treatment administration each day. Feces were evaluated for occult blood. Results of a CBC and serum biochemical analysis and measured N-acetyl-β-d-glucosaminidase (NAG) activity and whole blood clotting time were evaluated before, during, and after completion of treatments. Results of urinalysis and measured urine NAG activity were also evaluated. Birds treated with meloxicam had a significant increase in number of WBCs and decrease in PCV from before to after treatment. The PCV also decreased significantly, compared with results for the control group; however, WBC count and PCV for all birds remained within reference ranges throughout the study. One parrot treated with meloxicam had a single high value for urine NAG activity. Meloxicam administered orally at the dosage used in this study caused no apparent negative changes in several renal, gastrointestinal, or hemostatic variables in healthy Hispaniolan Amazon parrots. Additional studies to evaluate adverse effects of NSAIDs in birds will be needed.

  9. 5-FU Metabolism in Cancer and Orally-Administrable 5-FU Drugs

    Directory of Open Access Journals (Sweden)

    Iwao Sasaki

    2010-09-01

    Full Text Available 5-Fluorouracil (5-FU is a key anticancer drug that for its broad antitumor activity, as well as for its synergism with other anticancer drugs, has been used to treat various types of malignancies. In chemotherapeutic regimens, 5-FU has been combined with oxaliplatin, irinotecan and other drugs as a continuous intravenous infusion. Recent clinical chemotherapy studies have shown that several of the regimens with oral 5-FU drugs are not inferior compared to those involving continuous 5-FU infusion chemotherapy, and it is probable that in some regimens continuous 5-FU infusion can be replaced by oral 5-FU drugs. Historically, both the pharmaceutical industry and academia in Japan have been involved in the development of oral 5-FU drugs, and this review will focus on the current knowledge of 5-FU anabolism and catabolism, and the available information about the various orally-administrable 5-FU drugs, including UFT, S-1 and capecitabine. Clinical studies comparing the efficacy and adverse events of S-1 and capecitabine have been reported, and the accumulated results should be utilized to optimize the treatment of cancer patients. On the other hand, it is essential to elucidate the pharmacokinetic mechanism of each of the newly-developed drugs, to correctly select the drugs for each patient in the clinical setting, and to further develop optimized drug derivatives.

  10. Pharmacokinetics of oral neratinib during co-administration of ketoconazole in healthy subjects.

    Science.gov (United States)

    Abbas, Richat; Hug, Bruce A; Leister, Cathie; Burns, Jaime; Sonnichsen, Daryl

    2011-04-01

    The primary objective was to evaluate the pharmacokinetics of a single dose of neratinib, a potent, low-molecular-weight, orally administered, irreversible pan-ErbB (ErbB-1, -2, -4) receptor tyrosine kinase inhibitor, during co-administration with ketoconazole, a potent CYP3A4 inhibitor. This was an open-label, randomized, two-period, crossover study. Fasting healthy adults received a single oral dose of neratinib 240 mg alone and with multiple oral doses of ketoconazole 400 mg. Blood samples were collected up to 72 h after each neratinib dose. Plasma concentration data were analyzed using a noncompartmental method. The least square geometric mean ratios [90% confidence interval (CI)] of C(max) (neratinib+ketoconazole): C(max) (neratinib alone), and AUC(neratinib+ketoconazole): AUC(neratinib alone) were assessed. Twenty-four subjects were enrolled. Compared with neratinib administered alone, co-administration of ketoconazole increased neratinib C(max) by 3.2-fold (90% CI: 2.4, 4.3) and AUC by 4.8-fold (3.6, 6.5). Median t(max) was 6.0 h with both regimens. Ketoconazole decreased mean apparent oral clearance of neratinib from 346 lh(-1) to 87.1 lh(-1) and increased mean elimination half-life from 11.7 h to 18.0 h. The incidence of adverse events was comparable between the two regimens (50% neratinib alone, 65% co-administration with ketoconazole). Co-administration of neratinib with ketoconazole, a potent CYP3A inhibitor, increased neratinib C(max) by 3.2-fold and AUC by 4.8-fold compared with administration of neratinib alone. These results indicate that neratinib is a substrate of CYP3A and is susceptible to interaction with potent CYP3A inhibitors and, thus, dose adjustments may be needed if neratinib is administered with such compounds. © 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.

  11. Improved stability and antidiabetic potential of insulin containing folic acid functionalized polymer stabilized multilayered liposomes following oral administration

    DEFF Research Database (Denmark)

    Agrawal, Ashish Kumar; Harde, Harshad; Thanki, Kaushik

    2014-01-01

    The present study reports the folic acid (FA) functionalized insulin loaded stable liposomes with improved bioavailability following oral administration. Liposomes were stabilized by alternating coating of negatively charged poly(acrylic acid) (PAA) and positively charged poly(allyl amine...

  12. Failure mode and effects analysis applied to the administration of liquid medication by oral syringes

    Directory of Open Access Journals (Sweden)

    Eva María Guerra-Alia

    2017-11-01

    Full Text Available To carry out a Failure Mode and Effects Analysis (FMEA to the use of oral syringes. Methods: A multidisciplinary team was assembled within the Safety Committee. The stages of oral administration process of liquid medication were analysed, identifying the most critical and establishing the potential modes of failure that can cause errors. The impact associated with each mode of failure was calculated using the Risk Priority Number (RPN. Preventive actions were proposed. Results: Five failure modes were identified, all classified as high risk (RPN> 100. Seven of the eight preventive actions were implemented. Conclusions: The FMEA methodology was a useful tool. It has allowed to know the risks, analyse the causes that cause them, their effects on patient safety and the measures to reduce them

  13. Enhancement of the fibrinolytic activity in plasma by oral administration of nattokinase.

    Science.gov (United States)

    Sumi, H; Hamada, H; Nakanishi, K; Hiratani, H

    1990-01-01

    The existence of a potent fibrinolytic enzyme (nattokinase, NK) in the traditional fermented food called 'natto', was reported by us previously. It was confirmed that oral administration of NK (or natto) produced a mild and frequent enhancement of the fibrinolytic activity in the plasma, as indicated by the fibrinolytic parameters, and the production of tissue plasminogen activator. NK capsules were also administered orally to dogs with experimentally induced thrombosis, and lysis of the thrombi was observed by angiography. The results obtained suggest that NK represents a possible drug for use not only in the treatment of embolism but also in the prevention of the disease, since NK has a proven safety and can be massproduced.

  14. Interaction between Bisphosphonates and Mineral Water: Study of Oral Risedronate Absorption in Rats.

    Science.gov (United States)

    Itoh, Akihisa; Akagi, Yuuki; Shimomura, Hitoshi; Aoyama, Takao

    2016-01-01

    Bisphosphonates are antiosteoporotic agents prescribed for patients with osteoporosis. Drug package inserts for bisphosphonate supplements indicate that their bioavailability is reduced by high levels of metal cations (Ca(2+), Mg(2+), etc.). However, standards for these cations in water used for taking risedronate have not been defined. Here, we examined the effect of calcium and magnesium in mineral waters on the bioavailability of the third-generation bisphosphonate, risedronate, following oral administration in rats. As risedronate is unchanged and eliminated renally, risedronate absorption was estimated from the amount excreted in the urine. Risedronate was dissolved in mineral water samples and administered orally at 0.35 mg/kg. Urine samples were collected for 24 h after dosing. Risedronate was extracted from urine using ion-pair solid-phase cartridges and quantified by HPLC with UV detection (262 nm). Cumulative recovery of risedronate was calculated from the amount excreted in the urine. The 24-h recovery of risedronate from evian® (0.32±0.02% [mean±standard deviation (S.D.)], n=4) and Contrex(®) (0.22±0.05%) mineral waters was significantly lower than that from tap water (0.47±0.04%, pAbsorption of risedronate in calcium chloride and magnesium chloride aqueous solutions of the same hardness (822 mg/L) was 54% (0.27±0.04%) and 12% (0.51±0.08%) lower, respectively, compared with ultrapure water; suggesting that absorption of risedronate declines as the calcium concentration of mineral waters increases. Consumption of mineral waters containing high levels of calcium (80 mg/L or above), such as evian® and Contrex(®), is therefore not recommended when taking risedronate.

  15. Evaluation of student nurses' perception of preparedness for oral medication administration in clinical practice: a collaborative study.

    Science.gov (United States)

    Aggar, Christina; Dawson, Sonja

    2014-06-01

    Attainment of oral medication administration skills and competency for student nurses is challenging and medication errors are common. The ability of nurses to master a clinical skill is dependent upon educational instruction and practice. The aim of this study was to evaluate nursing students' perception of preparedness for oral medication administration in two practice environments and determine possible relationship between student demographics and their perceived preparedness for oral medication administration. This was a cross sectional, exploratory study. Eighty-eight second year students from a baccalaureate nursing course from two metropolitan Australian tertiary institutions participated. Student nurses' perception of preparedness for oral medication administration was measured via a self-administered, adapted, and validated questionnaire. The overall mean Total Preparedness Score was 86.2 (range 71-102). There was no significant difference for perceived total preparedness to administer oral medications between the two facilities. Whilst there was no significant relationship established between student demographics and their perceived preparedness to administer oral medications, four single questions related to clinical practice were shown to be significant. Low fidelity simulated teaching environments that incorporate time management and post medication situations, may improve student nurses' perceived preparedness for oral medication administration. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Human urinary excretion profile after smoking and oral administration of [14C]delta 1-tetrahydrocannabinol

    International Nuclear Information System (INIS)

    Johansson, E.; Gillespie, H.K.; Halldin, M.M.

    1990-01-01

    The urinary excretion profiles of delta 1-tetrahydrocannabinol (delta 1-THC) metabolites have been evaluated in two chronic and two naive marijuana users after smoking and oral administration of [ 14 C]delta 1-THC. Urine was collected for five days after each administration route and analyzed for total delta 1-THC metabolites by radioactivity determination, for delta 1-THC-7-oic acid by high-performance liquid chromatography, and for cross-reacting cannabinoids by the EMIT d.a.u. cannabinoid assay. The average urinary excretion half-life of 14 C-labeled delta 1-THC metabolites was calculated to be 18.2 +/- 4.9 h (+/- SD). The excretion profiles of delta 1-THC-7-oic acid and EMIT readings were similar to the excretion profile of 14 C-labeled metabolites in the naive users. However, in the chronic users the excretion profiles of delta 1-THC-7-oic acid and EMIT readings did not resemble the radioactive excretion due to the heavy influence from previous Cannabis use. Between 8-14% of the radioactive dose was recovered in the urine in both user groups after oral administration. Lower urinary recovery was obtained both in the chronic and naive users after smoking--5 and 2%, respectively

  17. Absorption of Bupivacaine after Administration of a Lozenge as Topical Treatment for Pain from Oral Mucositis.

    Science.gov (United States)

    Mogensen, Stine; Sverrisdóttir, Eva; Sveinsdóttir, Kolbrún; Treldal, Charlotte; Jensen, Kenneth; Jensen, Anders Bonde; Kristensen, Claus Andrup; Jacobsen, Jette; Kreilgaard, Mads; Petersen, Janne; Andersen, Ove

    2017-01-01

    The aim was to investigate systemic exposure after administration of a novel bupivacaine lozenge in healthy individuals with normal mucosa and in head and neck cancer (HNC) patients with oral mucositis. A lozenge containing 5, 10, 25 and 50 mg bupivacaine, respectively, was administered as single dose to 10 healthy individuals, and a lozenge containing 25 mg bupivacaine was administered as single dose to 10 HNC patients with oral mucositis and as multiple doses to five patients with HNC. Blood samples were collected for 6 hr from the healthy individuals and 3 hr from the patients with HNC, respectively, after administration. The plasma concentration-time profiles of bupivacaine were fitted to pharmacokinetic models using nonlinear mixed-effects modelling, evaluating demographics and health status as covariates. The population pharmacokinetics (PK) of bupivacaine lozenge was best described by a two-compartment distribution model with absorption transit compartments. All the observed plasma concentrations were well below the bupivacaine concentrations (2000-2250 ng/ml) which have caused toxic symptoms. The PK model suggested that relative bioavailability was two times higher in HNC patients with oral mucositis grade 1-2 and three times higher in HNC patients with oral mucositis grade 3-4 than in the healthy individuals. Simulations showed that the plasma concentrations would be below the toxic limit after repeated dosing every second hour with 25 mg bupivacaine for five days. The 25-mg bupivacaine lozenges were safe without systemic toxic levels of bupivacaine or risk of side effects. Based on PK simulations of repeated doses of 25 mg every two hours for 16 hr a day, the lozenges can be administered with minimum risk of exceeding the toxic limit. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  18. A Novel, Ecologically Relevant, Highly Preferred, and Non-invasive Means of Oral Substance Administration for Rodents

    OpenAIRE

    Sobolewski, Marissa; Allen, Joshua L.; Morris-Schaffer, Keith; Klocke, Carolyn; Conrad, Katherine; Cory-Slechta, Deborah A.

    2016-01-01

    Prenatal stress and nutrition are well-known to alter a broad range of physiological systems, notably metabolic, endocrine and neurobehavioral function. Commonly used methods for oral administration of xenobiotics can, by acting as a stressor or altering normal nutrition intake, alter these physiological systems as well. Taken together, oral administration methods may unintentionally introduce confounding physiological effects that can mask or enhance toxicity of xenobiotics, particularly if ...

  19. Use of 60Co panoramic source in the induction of oral mucositis in rats

    International Nuclear Information System (INIS)

    Andrade, Maira F.; Benetti, Carolina; Zezell, Denise M.; Correa, Luciana

    2013-01-01

    Oral Mucositis is a well-known side effect of chemo-radiotherapy in cancer patients or transplant recipients that could induce hospitalization or impairs therapy in different levels of severity. This study is devoted to define the first steps in the research of low level laser treatments in oral mucositis, proposing a 60 Co radiation to experimentally induce oral mucositis in rats using Panoramic gamma irradiator, simulating usual radiotherapy of head and neck cancer. Fifteen male Wistar rats, above 250g, were irradiated at Centro de Tecnologia das Radiacoes (IPEN - CNEN/SP) and divided in three experimental groups, with different single doses of radiation (30 Gy, 25 Gy and 20 Gy). The animals were observed for a 20 days period. Animals that received 30 Gy and 25 Gy developed greater severity of mucositis and premature euthanasia was performed in these groups on the 7th and 11th day after the irradiation, respectively. The 20 Gy group developed oral mucositis grading from moderated to severe between the days 7 and 11 after irradiation, with progressive body mass loss and decrease in the intake of food and water. These animals recovered from oral mucositis around the 18th day and clinical remission at the 20th day. The single dose of 20 Gy Gamma radiation proved to be efficient way for inducing oral mucositis in rats, allowing the establishment of an experimental model for oral mucositis in rats for future use on interventions of this serious aspect of radiation therapy, such as laser therapy using different wave lengths and power densities. (author)

  20. Use of {sup 60}Co panoramic source in the induction of oral mucositis in rats

    Energy Technology Data Exchange (ETDEWEB)

    Andrade, Maira F.; Benetti, Carolina; Zezell, Denise M., E-mail: mairandrade@yahoo.com, E-mail: zezell@usp.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Correa, Luciana, E-mail: lcorrea@usp.br [Universidade de Sao Paulo (FO/USP), Sao Paulo, SP (Brazil). Fac. de Odontologia

    2013-07-01

    Oral Mucositis is a well-known side effect of chemo-radiotherapy in cancer patients or transplant recipients that could induce hospitalization or impairs therapy in different levels of severity. This study is devoted to define the first steps in the research of low level laser treatments in oral mucositis, proposing a {sup 60}Co radiation to experimentally induce oral mucositis in rats using Panoramic gamma irradiator, simulating usual radiotherapy of head and neck cancer. Fifteen male Wistar rats, above 250g, were irradiated at Centro de Tecnologia das Radiacoes (IPEN - CNEN/SP) and divided in three experimental groups, with different single doses of radiation (30 Gy, 25 Gy and 20 Gy). The animals were observed for a 20 days period. Animals that received 30 Gy and 25 Gy developed greater severity of mucositis and premature euthanasia was performed in these groups on the 7th and 11th day after the irradiation, respectively. The 20 Gy group developed oral mucositis grading from moderated to severe between the days 7 and 11 after irradiation, with progressive body mass loss and decrease in the intake of food and water. These animals recovered from oral mucositis around the 18th day and clinical remission at the 20th day. The single dose of 20 Gy Gamma radiation proved to be efficient way for inducing oral mucositis in rats, allowing the establishment of an experimental model for oral mucositis in rats for future use on interventions of this serious aspect of radiation therapy, such as laser therapy using different wave lengths and power densities. (author)

  1. The influence of different pathogens on the lysozyme activity into tissues of rat oral cavity

    Directory of Open Access Journals (Sweden)

    A. P. Levitsky

    2017-08-01

    Full Text Available Aim: To determine action of the different pathogens on the lysozyme activity into tissues of oral cavity and serum. Methods: The lysozyme activities was determined into oral mucosa cheek, tongue gum and serum of 158 white rats (11 series experiments. The pathogens were used: atropine, protamine sulfat, indometacyn, bee poison, hydrasine sulfat, cytostatic cyclofosfan, lincomycin, lipopolysaccharide, composition of antibiotic and omeprasol for ACBT Results: The  whole of pathogens decreased lysozyme activity (mean in 1,6-2,5 times into oral tissues and on 16 % into serum. The specific lowering of lysozyme activities (Δ%/mg pathogen was low most for lipopolysaccharide, especially after oral application usage (exceeding was in tens times. Conclusion: The lysozyme activity lowering may play significant role in pathogenesis of stomatologic diseases/ Lipopolysaccharide (LPS send lysozyme activity lowering most especially after oral application. Probably, the antilysozyme action of pathogens realize by LPS. The stomatogenic factor in pathogenesis and profilactic of noninfection diseases is important.

  2. Oral administration of antimicrobials increase antimicrobial resistance in E. coli from chicken--a systematic review.

    Science.gov (United States)

    Simoneit, C; Burow, E; Tenhagen, B-A; Käsbohrer, A

    2015-01-01

    Antimicrobials play an important role in animal and human health care. It was the aim of this systematic review to assess the effects of oral administration of antimicrobials on the development of antimicrobial resistance (AMR) in Escherichia coli (E. coli) from chickens. Moreover, the effects of the administration of more than one antimicrobial and of different dosages were studied. Literature was searched in November 2012 from the electronic databases ISI Web of Science, PubMed, Scopus and a national literature database (DIMDI) as well as the database ProQuest LLC. The search was updated in March 2014. Original studies describing a treatment (A) and a control group of either non-treatment (C) or initial value (0) and determining AMR in E. coli at different sample points (SP) were included. The literature search resulted in 35 full text articles on the topic, seven (20%) of which contained sufficient information on the administered antimicrobial and the impact of treatment on AMR. Most papers described the use of more than one antimicrobial, several dosages, controls (non-treatment or pre-treatment) and measured AMR at different SPs leading to a total of 227 SPs on the impact of the use of antimicrobials on AMR in chickens. 74% of the SPs (168/227) described a higher AMR-rate in E. coli from treated animals than from controls. After the administration of a single antimicrobial, AMR increased at 72% of the SPs. Administration of more than one antimicrobial increased AMR at 82% of the SPs. Higher dosages were associated with similar or higher AMR rates. The limited number of studies for each antimicrobial agent and the high variability in the resistance effect call for more well designed studies on the impact of oral administration on AMR development and spread. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Studies on portal systemic circulation by oral administration of 201Tl enclosed enteric coated capsule

    International Nuclear Information System (INIS)

    Tonami, Norihisa; Nakajima, Kenichi; Watanabe, Naoto

    1986-01-01

    Thallium-201 enclosed enteric coated capsule was prepared and administered orally to evaluate portal systemic circulation in 11 control subjects and 31 patients with various liver diseases by investigating scintigraphic appearance and the heart-to-liver uptake ratio (H/L ratio). In 10 patients with liver cirrhosis and one with chronic hepatitis, the results of H/L ratio were compared to those obtained by 201 Tl per-rectal administration. 1. It was fundamentally confirmed that 201 Tl enclosed enteric coated capsule was not broken down in the artificial gastric juice, but nearly completely melted 15 minutes after soaking in the artificial intestinal juice. 2. Clinical study was successfully completed in 36 out of 42 cases (86 %). Unsuccessful cases were found in 2 with capsule collapse in the stomach and 4 with its poor moving to the duodenum. 3. In control subjects the liver was clearly visualized and the mean value of H/L ratio was 0.32 which is lower than that of 201 Tl per-rectal administration previously reported. H/L ratio in patients with chronic and acute hepatitis was nearly equal to that in control subjects. H/L ratio in patients with liver cirrhosis was slightly higher than that in control subjects, but there was no significant difference between them. In cases with esophageal varices, H/L ratio was not so high compared to that in control subjects. Out of 7 patients showing high H/L ratio more than 0.8 in 201 Tl per-rectal administration, only one showed similar high ratio (1.07) in oral administration of 201 Tl enclosed enteric coated capsule. In this case the shunting from superior mesenteric vein to inferior vena cava connection was confirmed. From these results, it was considered that the shunting volume of superior mesenteric vein through esophageal varices is small. 4. A possibility of a new administration of radioisotope with enteric coated capsule was emphasized. (author)

  4. A Study on the Single-dose Oral Toxicity of Super Key in Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Jinhee Kim

    2015-09-01

    Full Text Available Objectives: This study was performed to analyze the single-dose oral toxicity of the super key (processed sulfur. Methods: All experiments were conducted at Medvill, an institution authorized to perform non-clinical studies, under the Good Laboratory Practice (GLP regulations. In order to investigate the oral toxicity of super key We administered it orally to Sprague-Dawley (SD rats. The SD rats were divided into four groups of five male and five female animals per group: group 1 being the control group and groups 2, 3, and 4 being the experimental groups. Doses of super key 500 mg/kg, 1,000 mg/kg and 2,000 mg/kg were administered to the experimental groups, and a dose of normal saline solution, 10 mL/kg, was administered to the control group. We examined the survival rates, weights, clinical signs, gross findings and necropsy findings. This study was conducted under the approval of the Institutional Animal Ethics Committee. (Approval number: A01-14018. Results: No deaths or abnormalities occurred in any of the four groups. Although slight decreases in the weights of some female rats were noted, no significant changes in weights or differences in the gross findings between the control group and the experimental groups were observed. To check for abnormalities in organs, we used microscopy to examine representative histological sections of each specified organ; the results showed no significant differences in any of the organs. Conclusion: The results of this research showed that administration of 500 ─ 2,000 mg/kg of super key did not cause any changes in the weights or in the results of necropsy examinations. Neither did it result in any mortalities. The above findings suggest that treatment with super key is relatively safe. Further studies on this subject are needed to yield more concrete evidence.

  5. Oral administration of yessotoxin stabilizes E-cadherin in mouse colon

    International Nuclear Information System (INIS)

    Callegari, Federica; Sosa, Silvio; Ferrari, Sara; Soranzo, Maria Rosa; Pierotti, Silvia; Yasumoto, Takeshi; Tubaro, Aurelia; Rossini, Gian Paolo

    2006-01-01

    YTX has been shown to disrupt the E-cadherin-catenin system in cultured epithelial cells, raising some concern that ingestion of seafood contaminated by YTX might favour tumour spreading and metastasis formation in vivo. In order to probe whether YTX might affect cadherin systems in vivo, we have set up a study involving repeated oral dosing of the toxin in mice (1 mg/kg/day, for 7 days) and analysis of E-cadherin and N-cadherin in tissue extracts obtained at the end of the dosing scheme, as well as 1 and 3 months after YTX administration. We found that the E-cadherin pools obtained from lung and kidney were not altered by YTX in any of our experimental conditions. Extracts from mouse colon contained intact E-cadherin and an E-cadherin fragment of about 90 kDa (ECRA 9 ), displaying a molecular alteration resembling that caused by YTX in cultured cells. We found that the relative proportion of ECRA 9 , as compared to intact E-cadherin, was higher in colon extracts from control mice than from YTX-treated animals, indicating that oral administration of YTX to mice stabilizes E-cadherin of mouse colon. No significant difference could be detected in samples prepared from colons obtained 30 or 90 days after termination of YTX treatment. Oral administration of YTX to mice did not lead to a significant increase in the fragments of E-cadherin detectable in serum, neither it altered the N-cadherin pool of mouse heart. Electron microscopy analysis showed no substantial ultrastructural differences between controls and YTX-treated mice. Our findings show that ingestion of food contaminated by YTX poses a low risk of disruption of the E-cadherin system in vivo

  6. Effects of Oral Prednisone Administration on Serum Cystatin C in Dogs.

    Science.gov (United States)

    Muñoz, J; Soblechero, P; Duque, F J; Macías-García, B; Ruiz, P; Zaragoza, C; Barrera, R

    2017-11-01

    Oral administration of glucocorticoid alters serum cystatin C (sCysC) concentration in humans. To determine if oral administration of prednisone alters sCysC in dogs without pre-existing renal disease. Forty six dogs were included: 10 dogs diagnosed with steroid responsive meningitis arteritis (SRMA; group A), 20 dogs diagnosed of pituitary-dependent hyperadrenocorticism (PDH; group B), and 16 healthy control dogs (group C). Retrospective observational study. SRMA diagnosed dogs were administered prednisone 4 mg/kg/24 h PO 7 days, reducing the dose to 2 mg/kg/24 h 7 days before medication withdrawal. In group A, sampling was performed at days 0, 7, 14 and a final control at day 21. Blood and urine samples were collected in the 3 groups, and in group A, sampling was performed at all time points (days 1, 7, 14, and 21). In group A, sCysC was significantly higher at day 7 compared to the control group (0.4 ± 0.04 mg/L vs. 0.18 ± 0.03 mg/L mean ± SEM respectively P 0.05). Dogs with PDH included in group B did not have significant differences in sCysC (0.22 ± 0.03 mg/L) compared to control (P > 0.05). Oral administration of prednisone unlike altered endogenous glucocorticoid production, increases sCysC in dogs in a dose-dependent fashion. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  7. Pharmacokinetics of posaconazole in koalas (Phascolarctos cinereus) after intravenous and oral administration.

    Science.gov (United States)

    Gharibi, S; Kimble, B; Vogelnest, L; Barnes, J; Stadler, C K; Govendir, M

    2017-12-01

    The pharmacokinetic profile of posaconazole in clinically normal koalas (n = 8) was investigated. Single doses of posaconazole were administered intravenously (i.v.; 3 mg/kg; n = 2) or orally (p.o.; 6 mg/kg; n = 6) with serial plasma samples collected over 24 and 36 hr, respectively. Plasma concentrations of posaconazole were quantified by validated high-performance liquid chromatography. A noncompartmental pharmacokinetic analysis of data was performed. Following i.v. administration, estimates of the median (range) of plasma clearance (CL) and steady-state volume of distribution (V ss ) were 0.15 (0.13-0.18) L hr -1  kg -1 and 1.23 (0.93-1.53) L/kg, respectively. The median (range) elimination half-life (t 1/2 ) after i.v. and p.o. administration was 7.90 (7.62-8.18) and 12.79 (11.22-16.24) hr, respectively. Oral bioavailability varied from 0.43 to 0.99 (median: 0.66). Following oral administration, maximum plasma concentration (C max ; median: 0.72, range: 0.55-0.93 μg/ml) was achieved in 8 (range 6-12) hr. The in vitro plasma protein binding of posaconazole incubated at 37°C was 99.25 ± 0.29%. Consideration of posaconazole pharmacokinetic/pharmacodynamic (PK/PD) targets for some yeasts such as disseminated candidiasis suggests that posaconazole could be an efficacious treatment for cryptococcosis in koalas. © 2017 John Wiley & Sons Ltd.

  8. Drug distribution in spinal cord during administration with spinal loop dialysis probes in anaesthetized rats

    DEFF Research Database (Denmark)

    Uustalu, Maria; Abelson, Klas S P

    2007-01-01

    The present investigation aimed to study two methodological concerns of an experimental model, where a spinal loop dialysis probe is used for administration of substances to the spinal cord and sampling of neurotransmitters by microdialysis from the same area of anaesthetized rats. [(3)H]Epibatid......The present investigation aimed to study two methodological concerns of an experimental model, where a spinal loop dialysis probe is used for administration of substances to the spinal cord and sampling of neurotransmitters by microdialysis from the same area of anaesthetized rats. [(3)H...... intraspinal administration of substances through the spinal loop dialysis probe....

  9. Absorption of Bupivacaine after Administration of a Lozenge as Topical Treatment for Pain from Oral Mucositis

    DEFF Research Database (Denmark)

    Mogensen, Stine; Sverrisdóttir, Eva; Sveinsdóttir, Kolbrún

    2017-01-01

    The aim was to investigate systemic exposure after administration of a novel bupivacaine lozenge in healthy individuals with normal mucosa and in head and neck cancer (HNC) patients with oral mucositis. A lozenge containing 5, 10, 25 and 50 mg bupivacaine, respectively, was administered as single...... bupivacaine lozenges were safe without systemic toxic levels of bupivacaine or risk of side effects. Based on PK simulations of repeated doses of 25 mg every two hours for 16 hr a day, the lozenges can be administered with minimum risk of exceeding the toxic limit....

  10. Safety, efficacy and patient satisfaction with continuous daily administration of levonorgestrel/ethinylestradiol oral contraceptives

    Directory of Open Access Journals (Sweden)

    Giuseppe Benagiano

    2009-04-01

    Full Text Available Giuseppe Benagiano, Sabina Carrara, Valentina FilippiDepartment of Gynaecology and Obstetrics, Sapienza University, Rome, ItalyAbstract: The progestational steroid norgestrel was synthesized and tested between 1960 and 1965 through an international cooperation between Wyeth, USA and Schering, Berlin. It is a mixture of two “enantiomers,” with only one form (designated as levonorgestrel biologically active. When taken orally, it is rapidly absorbed, not subjected to a “first-pass” effect and is approximately 90% bioavailable, with a circulating half-life around 15 hours. Its contraceptive action is exerted at the central (hypothalamic and peripheral (cervical mucus and endometrium levels. Levonorgestrel (LNG, alone or in combination with ethinyl estradiol (EE, is the most widely employed contraceptive progestin: it is used in combined oral contraceptives, progestogen-only pills, long-acting contraceptive implants, intrauterine contraceptive systems and in emergency contraception. It is also the steroid of choice for new oral contraceptive regimens aimed at reducing the frequency of bleeding episodes. This novel approach, already tried more than 30 years ago, gained interest around the year 2000 when surveys of women’s attitudes toward monthly menstrual bleeding started to show a major change: more and more women declared that they would welcome a hormonal contraceptive method that reduced bleeding episodes to 4, 2 or even 1 per year. At this point, while the debate on the significance and “usefulness” of menstruation went on, attention focused on new regimens. The first new modality consisted of changing the 7-day medication-free interval, either shortening it to fewer than 7 days, or by the administration of low-dose estrogens during the interval between packages. Then, continuous administration regimens started to be investigated. This, however, did not happen suddenly, since, in specific situations, doctors had for years

  11. Absorption, Distribution, and Excretion of 14C-APX001 after Single-Dose Administration to Rats and Monkeys

    Science.gov (United States)

    Mansbach, Robert; Shaw, Karen J; Hodges, Michael R; Coleman, Samantha; Fitzsimmons, Michael E

    2017-01-01

    Abstract Background APX001 is a small-molecule therapeutic agent in clinical development for the treatment of invasive fungal infections (IFI). Methods The absorption, distribution and excretion profiles of [14C]APX001-derived radioactivity were determined in rats (albino and pigmented) and monkeys. Rats (some implanted with bile duct cannulae) were administered a single 100 mg/kg oral dose or a 30 mg/kg intravenous (IV) dose. Monkeys were administered a single 6 mg/kg IV dose. Samples of blood, urine, feces and bile, as well as carcasses, were collected through 168 hours after dosing. Samples were analyzed for total radioactivity content by liquid scintillation counting, and carcasses were analyzed by quantitative whole-body autoradiography. Results [14C]APX001-derived radioactivity was rapidly and extensively absorbed and extensively distributed to most tissues for both routes of administration in both species. In rats, tissues with the highest radioactivity Cmax values included bile, abdominal fat, reproductive fat, subcutaneous fat, and liver, but radioactivity was also detected in tissues associated with IFI, including lung, brain and eye. In monkeys, the highest Cmax values were in bile, urine, uveal tract, bone marrow, abdominal fat, liver, and kidney cortex. Liver and kidney were the tissues with highest radioactivity, but as in the rat, radioactivity was also detected in lung, brain and eye tissues. In pigmented rats, radiocarbon was densely distributed into pigmented tissue and more slowly cleared than from other tissues. Mean recovery of radioactivity in rats was approximately 95–100%. In bile duct-intact rats, >90% of radioactivity was recovered in feces. In cannulated rats, biliary excretion of radioactivity was the major route of elimination and accounted for 88.8% of the dose, whereas urinary and fecal excretion of radioactivity was minor and accounted for 2.56% and 5.42% of the dose, respectively. In monkeys, the overall recovery of radioactivity

  12. Absorption, distribution, metabolism and excretion of intravenously and orally administered tetrabromobisphenol A [2,3-dibromopropyl ether] in male Fischer-344 rats

    International Nuclear Information System (INIS)

    Knudsen, G.A.; Jacobs, L.M.; Kuester, R.K.; Sipes, I.G.

    2007-01-01

    Tetrabromobisphenol A bis[2,3-dibromopropyl ether],2,2-bis[3,5-dibromo-4-(2,3-dibromopropoxy)phenyl]propane is a brominated flame retardant with substantial U.S. production. Due to the likelihood of human exposure to TBBPA-DBPE and its probable metabolites, studies regarding the absorption, distribution, metabolism, and excretion were conducted. Male Fischer-344 rats were dosed with TBBPA-DBPE (20 mg/kg) by oral gavage or IV administration. Following a single oral administration of TBBPA-DBPE, elimination of [ 14 C] equivalents in the feces was extensive and rapid (95% of dose by 36 h). Following repeated daily oral doses for 5 or 10 days, route and rate of elimination was similar to single administrations of TBBPA-DBPE. After IV administration, fecal excretion of [ 14 C] equivalents was much slower (27% of dose eliminated by 36 h, 71% by 96 h). Urinary elimination was minimal ( 1/2β : 24.8 h; CL b : 0.1 mL min -1 . Kinetic constants following oral dosing were: t 1/2α : 2.5 h; t 1/2β : 13.9 h; CL b : 4.6 mL min -1 . Systemic bioavailability was 2.2%. Liver was the major site of disposition following oral or IV administration. After oral administration, 1% of the dose was eliminated in bile in 24 h (as metabolites). In in vitro experiments utilizing hepatocytes or liver microsomal protein, no detectable metabolism of TBBPA-DBPE occurred. These data indicate that TBBPA-DBPE is poorly absorbed from the gastrointestinal tract. Compound which is absorbed is sequestered in the liver, slowly metabolized, and eliminated in the feces

  13. Liver Iron Contents in Rats after Administration of Certain Iron ...

    African Journals Online (AJOL)

    The effect of consumption of certain iron compounds on liver iron deposition was ... extra iron probably depends on the type of food prepared, .... main groups. Each main group consisted of 4 subgroups. (8 rats per subgroup) which received the same basic diet but differing amounts of iron of a specific type. Each animal was ...

  14. Effects of acute and chronic administration of methylprednisolone on oxidative stress in rat lungs

    Directory of Open Access Journals (Sweden)

    Ronaldo Lopes Torres

    2014-06-01

    Full Text Available Objective: To determine the effects of acute and chronic administration of methylprednisolone on oxidative stress, as quantified by measuring lipid peroxidation (LPO and total reactive antioxidant potential (TRAP, in rat lungs. Methods: Forty Wistar rats were divided into four groups: acute treatment, comprising rats receiving a single injection of methylprednisolone (50 mg/kg i.p.; acute control, comprising rats i.p. injected with saline; chronic treatment, comprising rats receiving methylprednisolone in drinking water (6 mg/kg per day for 30 days; and chronic control, comprising rats receiving normal drinking water. Results: The levels of TRAP were significantly higher in the acute treatment group rats than in the acute control rats, suggesting an improvement in the pulmonary defenses of the former. The levels of lung LPO were significantly higher in the chronic treatment group rats than in the chronic control rats, indicating oxidative damage in the lung tissue of the former. Conclusions: Our results suggest that the acute use of corticosteroids is beneficial to lung tissue, whereas their chronic use is not. The chronic use of methylprednisolone appears to increase lung LPO levels.

  15. Acute cadmium administration to rats exerts both immunosuppressive and proinflammatory effects in spleen

    International Nuclear Information System (INIS)

    Demenesku, Jelena; Mirkov, Ivana; Ninkov, Marina; Popov Aleksandrov, Aleksandra; Zolotarevski, Lidija; Kataranovski, Dragan; Kataranovski, Milena

    2014-01-01

    Highlights: • The effect of cadmium on splenic T and innate immune cells in rats is explored. • Differential effects of 1 mg/kg on T cell and innate immune activities were shown. • Lower Cd dose (0.5 mg/kg) cause less pronounced immunosuppressive effects. • Proinflammatory effects on innate immune activities were seen at that dose. • Presented data depict complexity of immunomodulatory potential of this metal. - Abstract: Conflicting data (both suppression and augmentation as well as lack of the effect) exist in respect to cadmium (Cd) and splenic T cell-based immune cell activity. Spleen is also the site of innate immune responses but impact of Cd on this type of immunity has been less explored. In the present study the effects of acute Cd administration on basic aspects of both T cell-based and innate immune spleen cell activity were examined in rats. Intraperitoneal injection of 1 mg of Cd/kg resulted in decrease in concanavalin A (ConA) induced proliferation which seems to be more related to altered spleen cells responsiveness to IL-2 than to apoptosis. Differential effects on proinflammatory T cell derived cytokines were observed (decreases of IFN-γ gene expression and ConA-stimulated production, but increases in IL-17 mRNA levels with no effect on concentrations of protein product). Reduction of IFN-γ production seemed not to rely on IL-4 and IL-10, but at least partly on nitric oxide (NO). Increased activity relevant for innate immunity (granulocyte and CD11b + cell accumulation in the spleen, inducible nitric oxide synthase/iNOS expression and NO production by spleen cells) was observed, but there was a decrease in respiratory burst (dihydrorhodamine/DHR oxidation and nitroblue tetrazolium/NBT reduction). Increases of TNF-α and IL-1β gene expression and IL-1β protein product were noted as well. Administration of 0.5 mg Cd/kg resulted in less pronounced (ConA-induced proliferation) or lack of the effect (IFN-γ production) on spleen T cell

  16. Quercetin does not alter the oral bioavailability of Atorvastatin in rats.

    Science.gov (United States)

    Koritala, Rekha; Challa, Siva Reddy; Ragam, Satheesh Kumar; Geddam, Lal Babu; Venkatesh Reddy Challa, Venkatesh Reddy; Devi, Renuka; Sattenapalli, Srinu; Babu, Narendra

    2015-09-01

    The study was undertaken to evaluate the effect of Quercetin on the pharmacokinetics of Atorvastatin Calcium. In-vivo Pharmacokinetic studies were performed on rats in a single dose study and multiple dose study. Rats were treated with Quercetin (10 mg/kg) and Atorvastatin Calcium (20 mg/kg) orally and blood samples were collected at (0) pretreatment and 0.5, 1, 1.5, 2, 2.5, 3, 4, 8, 12, 24 hours post treatment. Plasma concentrations of Atorvastatin were estimated by HPLC method. Quercetin treatment did not significantly alter the pharmacokinetic parameters of atorvastatin like AUC(0-24), AUC(0-α) , T(max), C(max) and T(½) in both single dose and multiple dose studies of Atorvastatin Calcium. Quercetin does not alter the oral bioavailability of Atorvastatin Calcium in rats.

  17. Sedative and antinociceptive effects of dexmedetomidine and buprenorphine after oral transmucosal or intramuscular administration in cats.

    Science.gov (United States)

    Porters, Nathalie; Bosmans, Tim; Debille, Mariëlla; de Rooster, Hilde; Duchateau, Luc; Polis, Ingeborgh

    2014-01-01

    To compare sedation and antinociception after oral transmucosal (OTM) and intramuscular (IM) administration of a dexmedetomidine-buprenorphine combination in healthy adult cats. Randomized, 'blinded' crossover study, with 1 month washout between treatments. Six healthy neutered female cats, weighing 5.3-7.5 kg. A combination of dexmedetomidine (40 μg kg(-1) ) and buprenorphine (20 μg kg(-1) ) was administered by either the OTM (buccal cavity) or IM (quadriceps muscle) route. Sedation was measured using a numerical rating scale, at baseline and at various time points until 6 hours after treatment. At the same time points, analgesia was scored using a dynamic and interactive visual analogue scale, based on the response to an ear pinch, and by the cat's response to a mechanical stimulus exerted by a pressure rate onset device. Physiological and adverse effects were recorded, and oral pH measured. Signed rank tests were performed, with significance set at p < 0.05. Data are presented as median and range. There were no differences in sedation or antinociception scores between OTM and IM dosing at any of the time points. Nociceptive thresholds increased after both treatments but without significant difference between groups. Buccal pH remained between 8 and 8.5. Salivation was noted after OTM administration (n = 2) and vomiting after both OTM (n = 4), and IM (n = 3) dosing. In healthy adult cats, OTM administration of dexmedetomidine and buprenorphine resulted in comparable levels of sedation and antinociception to IM dosing. The OTM administration may offer an alternative route to administer this sedative-analgesic combination in cats. © 2013 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

  18. Chronic administration of sildenafil improves erectile function in a rat model of chronic renal failure

    Science.gov (United States)

    Gurbuz, Nilgun; Kol, Arif; Ipekci, Tumay; Ates, Erhan; Baykal, Asli; Usta, Mustafa F

    2015-01-01

    The relationship between erectile dysfunction (ED) and chronic renal failure (CRF) has been reported in several studies. This study aimed to investigate whether the chronic use of sildenafil could enhance the erectile capacity in CRF-induced rats. In addition, we assessed the effect of that treatment on certain molecules, which have been suggested to play crucial roles in erectile physiology and CRF-related ED as well. Three groups of animals were utilized: (1) age-matched control rats, (2) CRF-induced rats, (3) CRF-induced rats treated with chronic administration of sildenafil (5 mg kg−1 p.o. for 6 weeks [treatment started after 6 weeks of CRF induction]). At 3 months, all animals underwent cavernosal nerve stimulation (CNS) to assess erectile function. Penile tissue advanced glycation end products (AGE's)/5-hydroxymethyl-2-furaldehyde, malondialdehyde (MDA), cGMP (ELISA), inducible nitric oxide synthase (iNOS) and neuronal NOS (nNOS) (Western blot) analyses were performed in all rat groups. CRF-induced rats had a significant decrease in erectile function when compared to control rats (P chronic sildenafil administration on erectile function in CRF-induced rats. PMID:25652632

  19. Effects of the GABA(B) receptor agonist baclofen administered orally on normal food intake and intraperitoneally on fat intake in non-deprived rats.

    Science.gov (United States)

    Bains, Rasneer S; Ebenezer, Ivor S

    2013-01-05

    It has been previously reported that the GABA(B) receptor agonist baclofen decreases food intake after oral administration and fat intake after intraperitoneal administration. The aim of the study was to investigate the effects of baclofen (1-4 mg/ kg) administered orally (Experiment 1) on food intake in non-deprived rats (n=6) and intraperitoneally (Experiment 2) on fat intake in non-deprived rats (n=8) that were naïve to baclofen (1st set of trials) and in the same group of rats after they were sub-chronically exposed to baclofen (2nd set of trials). The results from Experiment 1 show that baclofen had no effects on food intake during the 1st set of trials, but the 2 and 4 mg/kg doses significantly increased food consumption during the 2nd set of trials. Baclofen produced sedation during the 1st set of trials, but tolerance occurred to this effect and was not apparent during the 2nd set of trials. These observations suggest that the motor effects may have competed with the hyperphagic effects of baclofen during the 1st set of trials. The data from Experiment 2 show that baclofen had no effects on fat intake during either the 1st or 2nd set of trials. The results of the study thus indicate that orally administrated baclofen increases food intake and intraperitoneal administration has no effect on fat intake in non-deprived rats under the conditions used in this study. These findings may have important implications for research on the use of baclofen in studies concerned with ingestive behaviours. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. Effect of gum arabic in an oral rehydration solution on recovery from diarrhea in rats.

    Science.gov (United States)

    Teichberg, S; Wingertzahn, M A; Moyse, J; Wapnir, R A

    1999-10-01

    It has been shown that gum arabic, a soluble fiber, enhances water, electrolyte, and glucose absorption from oral rehydration solutions in jejunal perfusion of healthy rats and in animals with theophylline-induced secretion or chronic osmotic-secretory diarrhea. This report concerns a study of the effectiveness of an oral rehydration solution supplemented with gum arabic, during recovery from chronic osmotic secretory diarrhea in free-living rats. Chronic diarrhea was induced in 60- to 80-g juvenile rats by providing a magnesium citrate-phenolphthalein solution as the sole fluid source for 7 days. This led to diarrhea characterized by dehydration, soft stools, increased cecal volume, decreased food and fluid intake and failure to gain weight. After 7 days of diarrhea, rats recovered for 24 hours with either tap water or an oral rehydration solution (90 mM Na, 111 mM glucose, 20 mM K, 80 mM chloride, 20 mM citrate) with or without 2.5 g/l gum arabic. Although all three solutions improved the diarrhea, optimal recovery from diarrhea was achieved with the gum arabic-supplemented oral rehydration solution. After 4 hours and 24 hours, rats drinking the gum arabic-supplemented solution gained more weight and had lower fecal output than rats receiving water or the rehydration solution without gum arabic. All three solutions normalized plasma osmolality after 24 hours. The positive effects of the gum arabic-supplemented rehydration solution on fluid and electrolyte absorption seen during jejunal perfusion also occurred during recovery from chronic osmotic secretory diarrhea, when free-living animals drank the solution ad libitum.

  1. Effect of oral administration of carprofen on intraocular pressure in normal dogs.

    Science.gov (United States)

    Meekins, J M; Overton, T L; Rankin, A J; Roush, J K

    2016-08-01

    The aim of this study was to determine the effect of oral administration of carprofen on intraocular pressure in normal dogs. Twelve young adult beagle dogs were randomly assigned to treatment (n = 6) or control (n = 6) groups. After an 11-day acclimation period, the treatment group received approximately 2.2 mg/kg carprofen per os every 12 h for 7 days, and the control group received a placebo gel capsule containing no drug per os every 12 h for 7 days. Intraocular pressure (IOP) was measured by a rebound tonometer at three time points per day (8 am, 2 pm, and 8 pm) during the acclimation (days 1-11) and treatment (days 12-18) phases and for 48 h (days 19-20) after the completion of treatment. There was no statistically significant change in IOP for either eye in the dogs receiving oral carprofen during the treatment phase (days 12-18). After day 4, no significant daily IOP changes were seen in control group dogs. Carprofen administered orally every 12 h for 7 days had no effect on IOP in normal beagle dogs. An acclimation period to frequent IOP measurements of at least 5 days is necessary to establish baseline IOP values and minimize possible anxiety-related effects on IOP measurements. © 2016 John Wiley & Sons Ltd.

  2. Oral administration of myostatin-specific recombinant Saccharomyces cerevisiae vaccine in rabbit.

    Science.gov (United States)

    Liu, Zhongtian; Zhou, Gang; Ren, Chonghua; Xu, Kun; Yan, Qiang; Li, Xinyi; Zhang, Tingting; Zhang, Zhiying

    2016-04-29

    Yeast is considered as a simple and cost-effective host for protein expression, and our previous studies have proved that Saccharomyces cerevisiae can deliver recombinant protein and DNA into mouse dendritic cells and can further induce immune responses as novel vaccines. In order to know whether similar immune responses can be induced in rabbit by oral administration of such recombinant S. cerevisiae vaccine, we orally fed the rabbits with heat-inactivated myostatin-recombinant S. cerevisiae for 5 weeks, and then myostatin-specific antibody in serum was detected successfully by western blotting and ELISA assay. The rabbits treated with myostatin-recombinant S. cerevisiae vaccine grew faster and their muscles were much heavier than that of the control group. As a common experimental animal and a meat livestock with great economic value, rabbit was proved to be the second animal species that have been successfully orally immunized by recombinant S. cerevisiae vaccine after mice. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. The studies of PLGA nanoparticles loading atorvastatin calcium for oral administration in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Zhenbao Li

    2017-05-01

    Full Text Available A biodegradable poly(lactic-co-glycolic acid loading atorvastatin calcium (AC nanoparticles (AC-PLGA-NPs were prepared by probe ultrasonication and evaporation method aiming at improving the oral bioavailability of AC. The effects of experimental parameters, including stabilizer species, stabilizer concentration and pH of aqueous phase, on particle size were also evaluated. The resultant nanoparticles were in spherical shape with an average diameter of 174.7 nm and a narrow particle size distribution. And the drug loading and encapsulation efficiency were about 8% and 71%, respectively. The particle size and polydispersion were almost unchanged in 10 days. The release curves of AC-PLGA-NPs in vitro displaying sustained release characteristics indicated that its release mechanisms were matrix erosion and diffusion. The pharmacokinetic study in vivo revealed that the Cmax and AUC0-∞ of AC-PLGA-NPs in rats were nearly 3.7-fold and 4.7-fold higher than that of pure atorvastatin calcium suspension. Our results demonstrated that the delivery of AC-PLGA-NPs could be a promising approach for the oral delivery of AC for enhanced bioavailability.

  4. Design and development of a lead jar for oral administration of radioiodine In hyperthyroid patients

    International Nuclear Information System (INIS)

    Rahman, M.S.; Paul, A.K.; Rahman, H.A.; Begum, F.

    2005-01-01

    Full text: Nuclear Medicine practices involve use of radioisotopes for diagnosis and treatment of diseases. Radioiodine is one of such radioisotopes, being used in the diagnosis and treatment of diseases since 1942. Handling of radioiodine involves radiation hazards both for the patients as well as for the technologists. Though radioiodine is supplied in a lead container, for treatment purpose, it is administered after dispensing into a glass jar that does not adequately protect radiation hazards. For this reason, we designed and developed a lead jar and radioiodine is dispensed into that lead jar to minimize radiation hazards. For oral administration of radioiodine to hyperthyroid patients, a lead jar was designed and developed with lead in Centre for Nuclear Medicine and Ultrasound, Khulna in December 2004 by own expertise and technologies in such a way that a glass jar could be introduced into that lead jar. The thickness of lead was 4.04 mm and the thickness of glass jar was 0.7 mm and thus the whole thickness of lead jar became 4.74 mm. The desired dose of radioiodine (8 mCi) that should be given to the patients were dispensed into that lead jar and administered orally to the patients. Radiation levels in 10 such cases were measured by Mini-Rad Series-1000 survey meter at 0.5 meter, 1 meter and 3 meters distances both lead jar and glass jar. The mean radiation level of lead jar and glass jar during oral administration of 8 mCi of Na 131 I solution in 10 cases at 0.5 meter, 1 meter and 3 meters distances were 62.4 ± 1.96 microSv/h, 17.7 ±1.95 microSv/h, 3.39 ± .12 microSv/h and 20.3± 2.16 microSv/h, 79.8 ± 0.79 microSv/h, 1.97 ± 0.23 microSv/h respectively. We have found that radiation level reduced by 67.47%, 61.58%, and 41.89% with lead jar at 0.5 meter, 1 meter and 3 meters distances. In conclusion, the locally designed and developed lead jar is safe, easy to handle and reduces radiation burden significantly in oral administration of radioiodine to

  5. Oral Administration of Astrovirus Capsid Protein Is Sufficient To Induce Acute Diarrhea In Vivo

    Directory of Open Access Journals (Sweden)

    Victoria A. Meliopoulos

    2016-11-01

    Full Text Available The disease mechanisms associated with the onset of astrovirus diarrhea are unknown. Unlike other enteric virus infections, astrovirus infection is not associated with an inflammatory response or cellular damage. In vitro studies in differentiated Caco-2 cells demonstrated that human astrovirus serotype 1 (HAstV-1 capsid protein alone disrupts the actin cytoskeleton and tight junction complex, leading to increased epithelial barrier permeability. In this study, we show that oral administration of purified recombinant turkey astrovirus 2 (TAstV-2 capsid protein results in acute diarrhea in a dose- and time-dependent manner in turkey poults. Similarly to that induced by infectious virus, TAstV-2 capsid-induced diarrhea was independent of inflammation or histological changes but was associated with increased intestinal barrier permeability, as well as redistribution of sodium hydrogen exchanger 3 (NHE3 from the membrane to the cytoplasm of the intestinal epithelium. Unlike other viral enterotoxins that have been identified, astrovirus capsid induces diarrhea after oral administration, reproducing the natural route of infection and demonstrating that ingestion of intact noninfectious capsid protein may be sufficient to provoke acute diarrhea. Based on these data, we hypothesize that the astrovirus capsid acts like an enterotoxin and induces intestinal epithelial barrier dysfunction.

  6. Pharmacokinetics of enrofloxacin after oral, intramuscular and bath administration in crucian carp (Carassius auratus gibelio).

    Science.gov (United States)

    Shan, Q; Fan, J; Wang, J; Zhu, X; Yin, Y; Zheng, G

    2018-02-01

    The pharmacokinetics of enrofloxacin (ENR) was studied in crucian carp (Carassius auratus gibelio) after single administration by intramuscular (IM) injection and oral gavage (PO) at a dose of 10 mg/kg body weight and by 5 mg/L bath for 5 hr at 25°C. The plasma concentrations of ENR and ciprofloxacin (CIP) were determined by HPLC. Pharmacokinetic parameters were calculated based on mean ENR or CIP concentrations using WinNonlin 6.1 software. After IM, PO and bath administration, the maximum plasma concentration (C max ) of 2.29, 3.24 and 0.36 μg/ml was obtained at 4.08, 0.68 and 0 hr, respectively; the elimination half-life (T 1/2β ) was 80.95, 62.17 and 61.15 hr, respectively; the area under the concentration-time curve (AUC) values were 223.46, 162.72 and 14.91 μg hr/ml, respectively. CIP, an active metabolite of enrofloxacin, was detected and measured after all methods of drug administration except bath. It is possible and practical to obtain therapeutic blood concentrations of enrofloxacin in the crucian carp using IM, PO and bath immersion administration. © 2017 John Wiley & Sons Ltd.

  7. Effect of intermittent oral administration of ponazuril on experimental Sarcocystis neurona infection of horses.

    Science.gov (United States)

    Mackay, Robert J; Tanhauser, Susan T; Gillis, Karen D; Mayhew, Ian G; Kennedy, Tom J

    2008-03-01

    To evaluate the effect of intermittent oral administration of ponazuril on immunoconversion against Sarcocystis neurona in horses inoculated intragastrically with S neurona sporocysts. 20 healthy horses that were seronegative for S neurona-specific IgG. 5 control horses were neither inoculated with sporocysts nor treated. Other horses (5 horses/group) each received 612,500 S neurona sporocysts via nasogastric tube (day 0) and were not treated or were administered ponazuril (20 mg/kg, PO) every 7 days (beginning on day 5) or every 14 days (beginning on day 12) for 12 weeks. Blood and CSF samples were collected on day - 1 and then every 14 days after challenge for western blot assessment of immunoconversion. Clinical signs of equine protozoal myeloencephalitis (EPM) were monitored, and tissues were examined histologically after euthanasia. Sera from all challenged horses yielded positive western blot results within 56 days. Immunoconversion in CSF was detected in only 2 of 5 horses that were treated weekly; all other challenged horses immunoconverted within 84 days. Weekly administration of ponazuril significantly reduced the antibody response against the S neurona 17-kd antigen in CSF. Neurologic signs consistent with EPM did not develop in any group; likewise, histologic examination of CNS tissue did not reveal protozoa or consistent degenerative or inflammatory changes. Administration of ponazuril every 7 days, but not every 14 days, significantly decreased intrathecal anti-S neurona antibody responses in horses inoculated with S neurona sporocysts. Protocols involving intermittent administration of ponazuril may have application in prevention of EPM.

  8. The effect of high-dose dronabinol (oral THC) maintenance on cannabis self-administration.

    Science.gov (United States)

    Schlienz, Nicolas J; Lee, Dustin C; Stitzer, Maxine L; Vandrey, Ryan

    2018-06-01

    There is a clear need for advancing the treatment of cannabis use disorders. Prior research has demonstrated that dronabinol (oral THC) can dose-dependently suppress cannabis withdrawal and reduce the acute effects of smoked cannabis. The present study was conducted to evaluate whether high-dose dronabinol could reduce cannabis self-administration among daily users. Non-treatment seeking daily cannabis users (N = 13) completed a residential within-subjects crossover study and were administered placebo, low-dose dronabinol (120 mg/day; 40 mg tid), or high-dose dronabinol (180-240 mg/day; 60-80 mg tid) for 12 consecutive days (order counterbalanced). During each 12-day dronabinol maintenance phase, participants were allowed to self-administer smoked cannabis containing <1% THC (placebo) or 5.7% THC (active) under forced-choice (drug vs. money) or progressive ratio conditions. Participants self-administered significantly more active cannabis compared with placebo in all conditions. When active cannabis was available, self-administration was significantly reduced during periods of dronabinol maintenance compared with placebo maintenance. There was no difference in self-administration between the low- and high-dose dronabinol conditions. Chronic dronabinol dosing can reduce cannabis self-administration in daily cannabis users and suppress withdrawal symptoms. Cannabinoid agonist medications should continue to be explored for therapeutic utility in the treatment of cannabis use disorders. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. The effects of honey and vitamin E administration on apoptosis in testes of rat exposed to noise stress

    Directory of Open Access Journals (Sweden)

    Masoud Hemadi

    2013-01-01

    Full Text Available Aims: A variety of stress factors are known to inhibit male reproductive functions. So this study was conducted in order to investigate the effects of honey and vitamin E on the germinative and somatic cells of testes of rats exposed to noise stress. Materials and Methods: Mature male wistar rats (n0 = 24 were randomly grouped as follows: Group 1 (honey + noise stress, 2 (vitamin E + noise stress, 3 (noise stress, and 4 as the control group. In groups 1, 2, and 3, rats were exposed to noise stress. In groups 1 and 2, rats also were given honey and vitamin E, respectively, orally for 50 days. After that, the germinative and somatic cells of testes parenchyma were isolated by digesting the whole testes by a standard method. Next, viability, apoptosis, and necrosis of the cells were evaluated by TUNEL kit and flow cytometry. Results: The rates of apoptosis and necrosis of the testicular cells were increased (P = 0.003 and P = 0.001, respectively, but viability of these cells decreased in testes of rats exposed to noise stress (P = 0.003. However, administration of honey and vitamin E were significantly helpful in keeping the cells of testis parenchyma alive, which suffers from noise pollution (P < 0.05 and P < 0.05, respectively. Conclusions: Noise stress has negative influences on the cells of testicular tissue by increasing apoptotic and necrotic cells. However, the associated enhancement in healthy cells suggests that honey and vitamin E have positive influences on the testis parenchyma.

  10. Dominant lethals following administration of tritium (THO) to rat males

    International Nuclear Information System (INIS)

    Yagova, A.; Baev, I.; Bajrakova, A.

    1976-01-01

    Adult rat males were given a single intraperitoneal tritium (THO) injection at 0,01 or 0,001 mCi/g body weight (1/100 or 1/1000 of LDsub(50/30), respectively). Twelve days after treatment each male was mated to 3-5 intact females, and the latter were replaced by fresh ones every 12 following days over a 120-day period. Mated females were killed to score conceptions, corpora lutea, and live and dead embryos. Estimations were made of F 1 prenatal death rate (according to Bateman, 1958) and the frequency of induction of dominant lethal mutations (according to Roehrborn, 1970). The results observed indicated paternal exposure to tritium (THO) to produce dominant lethals both in pre- and post-meiotic germ cells in the rat. The extent of the genetic damage studied was found to depend on the amount of activity administered as well as on the time interval between treatment and conception. (author)

  11. Oral administration of analgesia and anxiolysis for pain associated with bone marrow biopsy.

    Science.gov (United States)

    Talamo, Giampaolo; Liao, Jason; Bayerl, Michael G; Claxton, David F; Zangari, Maurizio

    2010-03-01

    Medical literature provides only scarce data about the degree of pain experienced by patients undergoing a bone marrow aspiration and biopsy (BMAB), and little is known about the factors that can modify the perception of pain. In this study, we evaluated the effectiveness of a combination of analgesia and anxiolysis in reducing the pain score of patients undergoing BMAB. Eighty-four consecutive adult patients underwent BMAB after local anesthesia with 5 mL of lidocaine hydrochloride 1% aqueous solution in the left posterior superior iliac crest. Analgesia was obtained with acetaminophen 650 mg and oxycodone 10 mg, and anxiolysis was obtained with lorazepam 2 mg, all drugs given once orally 30 min before the procedure. We assessed the pain level with the Wong-Baker Faces Pain Rating Scale, which distinguishes six levels of pain, from 0 to 5. The 34 patients who received an oral administration of analgesia and anxiolysis reported pain at lower levels, i.e., in the range of 0-2, more frequently than the 50 patients who underwent BMAB without analgesia/anxiolysis (78% vs 64%, respectively). Among several predictors analyzed using a multivariate regression model, three were found to be associated with decreased pain level: the use of analgesia/anxiolysis, male sex, and increase in age (all with p values <0.05). Length of the extracted bone specimen, body mass index, and need of a spinal needle for anesthesia in obese patients did not predict for pain level. An oral administration of prophylactic regimen of analgesia and anxiolysis, at the above-mentioned doses, produced a statistically significant reduction of the perception of pain in patients undergoing BMAB, but its effect did not seem to provide a major and clinically significant reduction of pain level.

  12. Water metabolism in rats subjected to chronic alcohol administration

    DEFF Research Database (Denmark)

    Parlesak, Alexandr; Pohl, C.; Bode, J.C.

    2004-01-01

    AIM: While the diuretic action of acute ingestion of alcohol has been studied extensively, the effect of chronic alcohol consumption has received less attention. The aim of the present study was to investigate the effect of chronic alcohol consumption on the balance of water intake and excretion ...... the body as hidden water loss increases after alcohol consumption by up to 25-26% over control values.......AIM: While the diuretic action of acute ingestion of alcohol has been studied extensively, the effect of chronic alcohol consumption has received less attention. The aim of the present study was to investigate the effect of chronic alcohol consumption on the balance of water intake and excretion...... and certain renal functions in rats during a period of 12 months. ANIMALS AND STUDY DESIGN: Male Wistar rats received either alcohol (15% v/v; group A, n = 65) or tap water (group C, n = 35) as drinking fluid. Urine and faeces were collected from 6 rats of each group during 7 days, at monthly intervals...

  13. Delayed nootropic effects of arginine vasopressin after early postnatal chronic administration to albino rat pups.

    Science.gov (United States)

    Kim, P A; Voskresenskaya, O G; Kamensky, A A

    2009-06-01

    Intranasal administration of arginine vasopressin (10 microg/kg) to albino rat pups had a strong nootropic effect during training with positive and negative reinforcement. This effect was different in animals of various age groups: training with positive reinforcement was improved in "adolescent" rats and pubertal animals, while during training with negative reinforcement, the nootropic effect of the peptide was more prolonged and persisted also in adult animals.

  14. Modulation of Rat Cecal Microbiota by Administration of Raffinose and Encapsulated Bifidobacterium breve

    OpenAIRE

    Dinoto, Achmad; Suksomcheep, Akarat; Ishizuka, Satoshi; Kimura, Hanae; Hanada, Satoshi; Kamagata, Yoichi; Asano, Kozo; Tomita, Fusao; Yokota, Atsushi

    2006-01-01

    To investigate the effects of administration of raffinose and encapsulated Bifidobacterium breve JCM 1192T cells on the rat cecal microbiota, in a preclinical synbiotic study groups of male WKAH/Hkm Slc rats were fed for 3 weeks with four different test diets: basal diet (group BD), basal diet supplemented with raffinose (group RAF), basal diet supplemented with encapsulated B. breve (group CB), and basal diet supplemented with both raffinose and encapsulated B. breve (group RCB). The bacteri...

  15. COMPUTER-ASSISTED SEMEN ANALYSIS OF RAT SPERMATOZOA AFTER AN INTRAPERITONEAL ADMINISTRATION OF INSECTICIDE DIAZINON

    Directory of Open Access Journals (Sweden)

    R. TOMAN

    2008-05-01

    Full Text Available The aim of this study was to reveal the effect of diazinon on the rat spermatozoa motility characteristics using the computer-assisted semen analysis (CASA. Motility, progressive motility, DAP, DCL, DSL, VAP, VCL, VSL, STR, LIN, WOB, ALH, and BCF after the diazinon i.p. administration of 20 mg/kg b.w. were evaluated. 36 hours after the diazinon administration, only slight decrease in VCL, DCL and increase in percentage of progressive motility in the diazinon-treated group. Significant decrease (P<0.01 was only observed in BCF in diazinon-treated group. Computer-assisted semen analysis (CASA of rat sperm motility showed that acute diazinon administration slightly affected the rat sperm motility which can be the first step in the decreased fertilization capacity caused by pesticides. Further investigation of reproductive effects of diazinon is needed.

  16. Reproductive toxicity in rats after chronic oral exposure to low dose of depleted uranium

    International Nuclear Information System (INIS)

    Li Rong; Ai Guoping; Xu Hui; Su Yongping; Cheng Tianmin; Leng Yanbing

    2007-01-01

    Objective: To study the reproductive toxicity in rats induced by low dose of depleted uranium (DU). Methods: Male and female rats(F 0 generation) were exposed to DU in food at doses of 0, 0.4, 4 and 40 mg·kg -1 ·d -1 for 160 days, respectively. Then the activities of enzymes in testis and sexual hormone contents in serum were detected. Mature male rats were mated with female rats exposed to the same doses for 14 days. Pregnant rate and normal labor rate in F 0 rats were detected, as well as the survival rate and weight of F 1 rats within 21 d after birth. Results: No adverse effects of DU on fertility were evident at any dose in F 0 rats. Compared with control group, the rate of pregnancy, normal labor, survival of offspring birth and offspring nurture in F 1 generation of high-dose group reduced to 40.0%, 33.3%, 33.3%, and 33.3%, respectively. The sexual hormone contents in F 0 generation exposed increased, but those in Fl rats decreased significantly. The activities of lactate dehydrogenase-X (LDH-X) decreased in F 1 rats exposed to high-dose of DU, and those of sorbitol dehydrogenase (SDH), LDH and Na + -K + -ATPase decreased in F 1 rats exposed to DU. Conclusions: Reproduction function, growth and development of F 0 rats are not obviously affected after chronic oral exposure to DU, while the toxicity effects in F 1 generation was observed at any dose. (authors)

  17. Disposition Kinetics of Amoxicillin in Healthy, Hepatopathic and Nephropathic Conditions in Chicken after Single Oral Administration

    Directory of Open Access Journals (Sweden)

    Moloy Kumar Bhar

    2010-12-01

    Full Text Available Fifteen broiler chickens (COBB 400 of 42 days of age weighing 1.8 to 2.0 kg were equally divided into 3 groups, each consisting of 5 birds. Hepatopathy was induced by oral administration of paracetamol while nephropathy was induced by intravenous administration of uranyl nitrate. Kinetic study was investigated in healthy, hepatopathic and nephropathic birds following single oral administration of amoxicillin at 40 mg kg-1. Blood samples were collected at different time schedule. Plasma concentrations of amoxicillin in healthy, hepatopathic and nephropathic birds were 41.90 ± 5.59, 9.93 ± 0.76 and 38.75 ± 6.08 µg ml-1, respectively at 1 hr; 15.34 ± 1.99, 18.57 ± 1.66 and 67.40 ± 2.62 µg ml-1, respectively at 4 hr and 2.03 ± 0.28, 15.54 ± 0.82 and 30.63 ± 1.58 µg ml-1, respectively at 24 hr. Maximum plasma concentration was detected at 1 hr in healthy birds (41.90 ± 5.59 µg ml-1 , at 8 hr in hepatopathic birds (23.51 ± 1.64 µg ml-1 and at 4 hr in nephropathic birds (67.40 ± 2.62 µg ml-1. The drug could not be detected in plasma beyond 24 hr in healthy, 72 hr in both hepatopathic and nephropathic birds. The concentration of amoxicillin was significantly (P < 0.01 higher in most of the samples of hepatopathic and nephropathic birds compared to healthy birds. Significant higher values (P < 0.01 of t1/2 K, AUC, and MRT and lower values of K and ClB in the hepatopathic and nephropathic birds in comparison to healthy birds were observed.

  18. Comparative Pharmacokinetics of Levofloxacin in Healthy and Renal Damaged Muscovy Ducks following Intravenous and Oral Administration

    Directory of Open Access Journals (Sweden)

    Mohamed Aboubakr

    2014-01-01

    Full Text Available The pharmacokinetics aspects of levofloxacin were studied in healthy and experimentally renal damaged Muscovy ducks after single intravenous (IV and oral (PO dose of 10 mg kg−1 bwt. Following IV administration, elimination half-life (t1/2(β and mean residence time (MRT were longer in renal damaged ducks than in healthy ones. Total clearance (Cltot in renal damaged ducks (0.20 L kg−1 h−1 was significantly lower as compared to that in healthy ones (0.41 L kg−1 h−1. Following PO administration, the peak serum concentration (Cmax was higher in renal damaged than in healthy ducks and was achieved at maximum time (tmax of 2.47 and 2.05 h, respectively. The drug was eliminated (t1/2(el at a significant slower rate (3.94 h in renal damaged than in healthy ducks (2.89 h. The pharmacokinetic profile of levofloxacin is altered in renal damaged ducks due to the increased serum levofloxacin concentrations compared with that in clinically healthy ducks. Oral administration of levofloxacin at 10 mg kg−1 bwt may be highly efficacious against susceptible bacteria in ducks. Also, the dose of levofloxacin should be reduced in renal damaged ducks. Pharmacokinetic/pharmacodynamic integration revealed significantly higher values for Cmax/MIC and AUC/MIC ratios in renal damaged ducks than in healthy ones, indicating the excellent pharmacokinetic characteristics of levofloxacin in renal damaged ducks.

  19. Pharmacokinetics of dextromethorphan and its metabolites in horses following a single oral administration.

    Science.gov (United States)

    Corado, Carley R; McKemie, Daniel S; Knych, Heather K

    2017-06-01

    Dextromethorphan is an N-methyl-D-aspartate (NMDA) non-competitive antagonist commonly used in human medicine as an antitussive. Dextromethorphan is metabolized in humans by cytochrome P450 2D6 into dextrorphan, which is reported to be more potent than the parent compound. The goal of this study is to describe the metabolism of and determine the pharmacokinetics of dextromethorphan and its major metabolites following oral administration to horses. A total of 23 horses received a single oral dose of 2 mg/kg. Blood samples were collected at time 0 and at various times up to 96 h post drug administration. Urine samples were collected from 12 horses up to 120 h post administration. Plasma and urine samples were analyzed using liquid chromatography-mass spectrometry, and the resulting data analyzed using non-compartmental analysis. The C max , T max , and the t 1/2 of dextromethorphan were 519.4 ng/mL, 0.55 h, and 12.4 h respectively. The area under the curve of dextromethorphan, free dextrorphan, and conjugated dextrorphan were 563.8, 2.19, and 6,691 h*ng/mL respectively. In addition to free and glucuronidated dextrorphan, several additional glucuronide metabolites were identified in plasma, including hydroxyl-desmethyl dextrorphan, desmethyl dextrorphan, and three forms of hydroxylated dextrorphan. Dextromethorphan was found to be eliminated from the urine predominately as the O-demethylated metabolite, dextrorphan. Several additional metabolites including several novel hydroxy-dextrorphan metabolites were also detected in the urine in both free and glucuronidated forms. No significant undesirable behavioural effects were noted throughout the duration of the study. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  20. Effects of long-term administration of a cocoa polyphenolic extract (Acticoa powder) on cognitive performances in aged rats.

    Science.gov (United States)

    Bisson, Jean-François; Nejdi, Amine; Rozan, Pascale; Hidalgo, Sophie; Lalonde, Robert; Messaoudi, Michaël

    2008-07-01

    Numerous studies have indicated that increased vulnerability to oxidative stress may be the main factor involved in functional declines during normal and pathological ageing, and that antioxidant agents, such as polyphenols, may improve or prevent these deficits. We examined whether 1-year administration of a cocoa polyphenolic extract (Acticoa powder), orally delivered at the dose of 24 mg/kg per d between 15 and 27 months of age, affects the onset of age-related cognitive deficits, urinary free dopamine levels and lifespan in old Wistar-Unilever rats. Acticoa powder improved cognitive performances in light extinction and water maze paradigms, increased lifespan and preserved high urinary free dopamine levels. These results suggest that Acticoa powder may be beneficial in retarding age-related brain impairments, including cognitive deficits in normal ageing and perhaps neurodegenerative diseases. Further studies are required to elucidate the mechanisms of cocoa polyphenols in neuroprotection and to explore their effects in man.

  1. Nanosuspension of Phyllanthus amarus extract for improving oral bioavailability and prevention of paracetamol induced hepatotoxicity in Sprague–Dawley rats

    International Nuclear Information System (INIS)

    Mishra, Shanti Bhushan; Pandey, Himanshu; Pandey, Avinash C

    2013-01-01

    Phyllanthus amarus (P. amarus) is commonly used for traditional Indian medicine and as dietary adjuncts for the treatment of numerous physiological disorders including hepatic disorders. Due to the poor water solubility of its major constituents such as lignans and flavonoids, its absorption upon oral administration could be limited. The present study was designed to evaluate and compare the hepatoprotective effects of the ethanolic extract of P. amarus (PAE) and its nanoparticles (PAN) on paracetamol induced acute liver toxicity in Sprague–Dawley rats. An oral dose of PAE at 125 and 250 mg kg −1 and PAN at 25 and 50 mg kg −1 showed a significant hepatoprotective effect relatively to the same extent (P −1 PAN was effectively better than 125 mg kg −1 PAE (P < 0.001), and an oral dose of PAN that is five times less than PAE could exhibit similar levels of outcomes. In conclusion, we suggest that the nanoparticles system can be applied to overcome other poorly water soluble herbal medicines and furthermore to decrease the treatment dosage. (paper)

  2. Acute oral safety study of sodium caseinate glycosylated via maillard reaction with galactose in rats.

    Science.gov (United States)

    Anadón, Arturo; Martínez, Maria A; Ares, Irma; Castellano, Victor; Martínez-Larrañaga, Maria R; Corzo-Martínez, Marta; Moreno, F Javier; Villamiel, Mar

    2014-03-01

    In order to potentially use sodium caseinate (SC) glycated with galactose (Gal) in the food industry as a new functional ingredient with proved technological and biological properties, an evaluation of oral acute toxicity has been carried out. An acute safety study with SC-Gal glycoconjugates in the Wistar rat with a single oral gavage dose of 2,000 mg/kg of body weight was conducted. The SC-Gal glycoconjugates were well tolerated; no adverse effects or mortality was observed during the 2-week observation period. No abnormal signs, behavioral changes, body weight changes, or alterations in food and water consumption occurred. After this period, no changes in hematological and serum chemistry parameters, organ weights, or gross pathology or histopathology were detected. It was concluded that SC-Gal glycoconjugates obtained via the Maillard reaction were well tolerated in rats at an acute oral dose of 2,000 mg/kg of body weight. The SC-Gal glycoconjugates have a low order of acute toxicity, and the oral 50 % lethal dose for male and female rats is in excess of 2,000 mg/kg of body weight.

  3. Acute and subchronic oral toxicity studies in rats of a hydrolyzed chicken sternal cartilage preparation.

    Science.gov (United States)

    Schauss, A G; Merkel, D J; Glaza, S M; Sorenson, S R

    2007-02-01

    Two acute and subchronic oral toxicity studies were conducted in rats to evaluate safety of a patented preparation of hydrolyzed chicken sternal cartilage (BioCell Collagen II) containing collagen type II, chondroitin sulfate, and hyaluronic acid. In the acute oral toxicity study, five males and five females of Sprague-Dawley rats were administered a single dose of 5000 mg of the test product per kg body weight and observed for 14 days. All animals survived and exhibited normal body weight gain throughout the study. Macroscopic necropsy examination conducted on day 15 revealed no gross pathological lesions in any of the animals. In the subchronic study, Sprague-Dawley rats (40 males, 40 females) were divided into four same-sex groups (10 animals/group). Animals in each group were administered daily either 0, 30, 300 or 1000 mg of the test product per kg of body weight for over 90 days. All animals survived and showed no significant changes in their body weights and histopathology. Although some differences were observed between the treated and control animals in several parameters, they were generally not dose-related or considered to be of toxicological significance. In conclusion, the results from the two oral toxicity studies with male and female young adult rats indicated that the test preparation from hydrolyzed chicken sternal cartilage collagen (BioCell Collagen II) was well tolerated at all four doses tested.

  4. Antifungal treatment with carvacrol and eugenol of oral candidiasis in immunosuppressed rats

    Directory of Open Access Journals (Sweden)

    N. Chami

    Full Text Available Carvacrol and eugenol, the main (phenolic components of essential oils of some aromatic plants, were evaluated for their therapeutic efficacy in the treatment of experimental oral candidiasis induced by Candida albicans in immunosuppressed rats. This anticandidal activity was analyzed by microbiological and histopathological techniques, and it was compared with that of nystatin, which was used as a positive control. Microbiologically, carvacrol and eugenol significantly (p<0.05 reduced the number of colony forming units (CFU sampled from the oral cavity of rats treated for eight consecutive days, compared to untreated control rats. Treatment with nystatin gave similar results. Histologically, the untreated control animals showed numerous hyphae on the epithelium of the dorsal surface of the tongue. In contrast no hyphal colonization of the epithelium was seen in carvacrol-treated animals, while in rats treated with eugenol, only a few focalized zones of the dorsal surface of the tongue were occupied by hyphae. In the nystatin treated group, hyphae were found in the folds of the tongue mucosa. Thus, the histological data were confirmed by the microbiological tests for carvacrol and eugenol, but not for the nystatin-treated group. Therefore, carvacrol and eugenol could be considered as strong antifungal agents and could be proposed as therapeutic agents for oral candidiasis.

  5. Acute and Subacute Oral Toxicity of Periodate in Rats

    Science.gov (United States)

    2014-11-17

    associated with kidney disease are characterized by activation of the innate immune system coupled with immune deficiency. Sodium periodate exposed rats...lymphocytes in splenic nodules and was coded as white pulp atrophy. White pulp atrophy was noted in one of 10 females in the 40 mg/kg-day group and...and white cell precursors) and contracted sinuses or red pulp atrophy was noted in four of 10 females in the 318 mg/kg-day group. Red pulp atrophy was

  6. [Changes in serum lipids in rats treated with oral cooper].

    Science.gov (United States)

    Alarcón-Corredor, O M; Carnevalí de Tatá, E; Reinosa-Füller, J; Contreras, Y; Ramírez de Fernández, M; Yánez-Domínguez, C

    2000-09-01

    Disturbances in lipid metabolism during copper deficiency in rats are well recognized. Copper deficiency is associated with the spontaneous retention of hepatic iron. Previous studies have reported that hypercholesterolemia and hypertriglyceridemia are associated with elevated hepatic iron concentrations in copper deficient rats. There was a direct relationship between the magnitude of blood lipids and the concentration of hepatic iron. Based on these data, it has been hypothesized that iron was responsible for the development of lipemia of copper deficiency. In this study was determined the effect of increasing doses of Cu(10, 20 and 50 ppm) in the diet, on the serum total lipids, total cholesterol, triglycerides (triacylglicerols), phospholipids, non-esterified fatty acids (NEFA) and liver iron and zinc concentrations in normal rats. The results were compared with normal rats that received a balanced diet containing 0.6 and 6 ppm of Cu, respectively. The results show that Cu-supplement diminished the cholesterol and triglyceride serum levels, increased the level of phospholipids, NEFA and concomitantly decreased the hepatic concentrations of Fe and Zn. There was a statistically significant (p Cu (r = -0.612), liver Fe and liver Zn (r = 0.837), liver Cu and liver Zn (r = -0.612), and serum triglycerides and liver Zn (r = 0.967). The mechanism(s) by which Fe and Zn determine these changes is not known; none of the