1
40
1
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1016/j.taap.2016.08.025" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/j.taap.2016.08.025</a>
Pages
55–62
Volume
309
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Ocular toxicity of AUY922 in pigmented and albino rats.
Publisher
An entity responsible for making the resource available
Toxicology and applied pharmacology
Date
A point or period of time associated with an event in the lifecycle of the resource
2016
2016-10
Subject
The topic of the resource
*AUY922; *Electroretinography; *Histopathology; *HSP90 inhibitor; *Ocular toxicity; *Rodents; Animals; Electroretinography; Eye/*drug effects/physiopathology; Isoxazoles/toxicity; Rats; Resorcinols/toxicity; Wistar
Creator
An entity primarily responsible for making the resource
Roman Danielle; VerHoeve James; Schadt Heiko; Vicart Axel; Walker Ursula Junker; Turner Oliver; Richardson Terrilyn A; Wolford Suzanne T; Miller Paul E; Zhou Wei; Lu Hong; Akimov Mikhail; Kluwe William
Description
An account of the resource
AUY922, a heat shock protein 90 inhibitor is associated with ocular adverse events (AEs). To provide a better understanding of ocular AEs in patients, 4 investigative studies were performed in a step-wise approach to assess retinal structure and function in pigmented (Brown Norway) and albino (Wistar) rats. In rats administered 30mg/kg of AUY922, the AUC0-24h and Cmax are comparable to that in patients at 70mg/m(2). AUY922 at \textgreater/=30mg/kg was poorly tolerated by rats with morbidity or mortality generally after the third weekly treatment. Electroretinography (ERG) changes were observed at doses \textgreater/=30mg/kg. The ERG changes were dose dependent, consistent with an effect on the photoreceptors, and fully reversible. The ERG effects could not be minimized by decreasing the Cmax while maintaining AUC. Histopathological changes were seen mainly when rats were administered AUY922 at 100mg/kg. The 2-hour infusion of AUY922 at 100mg/kg caused disorganization of the outer segment photoreceptor morphology in male Brown Norway rats; the severity of the disorganization increased with the number of administrations, but was reversible during a 4-week posttreatment period. There was no major difference in ocular response between Brown Norway and Wistar rats. No changes in serum iron levels, and no changes in rhodopsin, PDE6alpha, beta-transducin concentrations, or retinal pigment epithelium-specific protein RPE65 expression were observed after single and multiple infusions of AUY922 at 100mg/kg compared to vehicle-treated controls. AUY922 retinal toxicity in rats recapitulates and further characterizes that reported in patients and is shown to be reversible, while a precise molecular mechanism for the effect was not determined.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1016/j.taap.2016.08.025" target="_blank" rel="noreferrer noopener">10.1016/j.taap.2016.08.025</a>
Rights
Information about rights held in and over the resource
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
*AUY922
*Electroretinography
*Histopathology
*HSP90 inhibitor
*Ocular toxicity
*Rodents
2016
Akimov Mikhail
Animals
Department of Pharmaceutical Sciences
Electroretinography
Eye/*drug effects/physiopathology
Isoxazoles/toxicity
Kluwe William
Lu Hong
Miller Paul E
NEOMED College of Pharmacy
Rats
Resorcinols/toxicity
Richardson Terrilyn A
Roman Danielle
Schadt Heiko
Toxicology and applied pharmacology
Turner Oliver
VerHoeve James
Vicart Axel
Walker Ursula Junker
Wistar
Wolford Suzanne T
Zhou Wei