Thofner I.C.N.,Copenhagen University |
Liebhart D.,University of Veterinary Medicine Vienna |
Hess M.,University of Veterinary Medicine Vienna |
Schou T.W.,Environment and Toxicology |
And 7 more authors.
Avian Pathology | Year: 2012
Five different Artemisia annua-derived materials (i.e. dry leaves, pure artemisinin, and hexane, dichloromethane or methanol extracts of leaves) were screened for their in vitro activities against six clonal cultures of Histomonas meleagridis. Except for the methanol extract, all tested materials displayed in vitro activity against all tested protozoal clones. Neither the dry plant material, extracts nor artemisinin showed any antibacterial activity against the xenic bacteria accompanying the six H. meleagridis clones at concentration levels identical to the antihistomonal setting. The dichloromethane extract of dry leaves (Ext-DCM) (minimal lethal concentration=1.0 mg/ml) and artemisinin (half-maximal inhibitory concentration=1.295 mg/ml) had the most promising antihistomonal properties and were therefore subsequently tested in a standardized experimental infection model in both turkeys and chickens infected with clonal H. meleagridis. There were no differences between treatment groups, where all infected turkeys showed severe clinical histomonosis and demonstrated severe typhlohepatitis typical for histomonosis. Consistent with the infection model used, the infected chickens did not show any adverse clinical signs but contracted severe lesions in their caeca 7 and 10 days post infection (d.p.i.), liver lesions were absent to mild after 7 d.p.i. and progressed to severe lesions at 10 d.p.i.; thus no differences between treatment groups were observed. In conclusion, neither artemisinin nor Ext-DCM was able to prevent experimental histomonosis in turkeys and chickens at the given concentrations, which is contrary to the antihistomonal effect noticed in vitro even though the same clonal culture was used. The results of this study therefore clearly demonstrate the importance of defined in vivo experimentation in order to assess and verify in vitro results. © 2012 Copyright Houghton Trust Ltd.
Hadrup N.,Technical University of Denmark |
Gao X.,CAS Institute of High Energy Physics |
Lam H.R.,Environment and Toxicology |
Loeschner K.,Technical University of Denmark |
And 7 more authors.
Archives of Toxicology | Year: 2012
Subacute toxicity of 14 nm nanoparticulate silver (Ag-NP) stabilised with polyvinylpyrrolidone and ionic silver in the form of silver acetate (Ag-acetate) was investigated in four-week-old Wistar rats. Animals received orally by gavage the following: vehicle control (10 ,6); Ag-NP at doses: 2.25 (8 ), 4.5 (8 ) or 9 mg/kg bw/day (10 ,6); or Ag-acetate 9 mg silver/kg bw/day (8 ) for 28 days. Clinical, haematolological and biochemical parameters, organ weights, macro- and microscopic pathological changes were investigated. Caecal bacterial phyla and their silver resistance genes were quantified. For the Ag-NP groups, no toxicological effects were recorded. For Ag-acetate, lower body weight gain (day 4-7, 11-14, 14-16, P < 0.05; overall, day 1-28, P < 0.01), increased plasma alkaline phosphatase (P < 0.05), decreased plasma urea (P < 0.05) and lower absolute (P < 0.01) and relative (P <0.05) thymus weight were recorded. In conclusion, these findings indicate toxicity of 9 mg/kg bw/day ionic silver but not of an equimolar AgNP dose. This is in accordance with previously reported data showing that oral Ag-acetate, in comparison with an equimolar dose of Ag-NP, resulted in higher silver plasma and organ concentrations. © Springer-Verlag 2011.
Knudsen K.B.,Copenhagen University |
Knudsen K.B.,Helmholtz Center Munich |
Northeved H.,H. Lund beck A S |
Gjetting T.,Technical University of Denmark |
And 5 more authors.
Journal of Nanoparticle Research | Year: 2014
We investigated the biodistribution following the administration of nanosized (about 50 and 90 nm) cationic (ζ: +30 and +50 mV) micelles and liposomes intended for drug delivery. The particles were stable and well characterized with respect to size and ζ potential. Ten 5- to 6-week-old male rats were used. The animals were randomly allocated to five groups receiving either cationic micelles or cationic liposomes by single intravenous (IV) administration at a dose of 100 mg/kg bodyweight by single intracerebroventricular (ICV) injection at a dose of 50 μg or no treatment. ICV administration was used to study local distribution in the brain and IV administration to study the systemic distribution of the particles. For both types of particles, ICV administration showed distribution in all ventricles in the brain while IV delivery displayed distribution to the major organs liver, spleen, kidney and lung, but not to the brain. Our data suggest that cationic micelles and liposomes are widely distributed in the body, indicating that these could potentially be used as drug delivery carriers to the major organs, but they do not cross the blood-brain barrier to a significant extent, without a targeting ligand attached. However, they are able to persist in the ventricles of the brain up to 24 h after ICV administration, demonstrating a new ability. © 2014 Springer Science+Business Media Dordrecht.
Knudsen K.B.,Copenhagen University |
Knudsen K.B.,Lundbeck |
Northeved H.,Lundbeck |
Ek P.K.,Technical University of Denmark |
And 6 more authors.
Nanotoxicology | Year: 2014
We investigated the potential for systemic and local toxicity after administration of empty nanosized anionic and cationic PEGylated-micelles and non-PEGylated liposomes, without a ligand attached, intended for use in drug-delivery systems. The particles were administered to 5-6-week-old male rats by three intravenous (IV) administrations over a period of one week at a dose of 100 mg/kg bodyweight or after a single intracerebroventricular (ICV) injection at a dose of 50 μg. The particles were stable and well characterised with respect to size and zeta potential. ICV administration of cationic particles was associated with histological changes near the injection site (hippocampus). Here, we detected focal infiltration with phagocytic cells, loss of neurons and apoptotic cell death, which were not observed after administration of the vehicle. No significant difference was found after IV or ICV administration of the anionic micelles with regard to haematology, clinical chemistry parameters or at the pathological examinations, as compared to control animals. Our study suggests that ICV delivery of cationic particles to the brain tissue is associated with toxicity at the injection site. © 2014 Informa UK, Ltd.
PubMed | Environment and Toxicology and Technical University of Denmark
Type: Journal Article | Journal: Regulatory toxicology and pharmacology : RTP | Year: 2014
Orally administered silver has been described to be absorbed in a range of 0.4-18% in mammals with a human value of 18%. Based on findings in animals, silver seems to be distributed to all of the organs investigated, with the highest levels being observed in the intestine and stomach. In the skin, silver induces a blue-grey discoloration termed argyria. Excretion occurs via the bile and urine. The following dose-dependent animal toxicity findings have been reported: death, weight loss, hypoactivity, altered neurotransmitter levels, altered liver enzymes, altered blood values, enlarged hearts and immunological effects. Substantial evidence exists suggesting that the effects induced by particulate silver are mediated via silver ions that are released from the particle surface. With the current data regarding toxicity and average human dietary exposure, a Margin of Safety calculation indicates at least a factor of five before a level of concern to the general population is reached.