D‐α‐tocopheryl polyethylene glycol 1000 succinate‐containing vehicles provide no detectable chemoprotection from oxidative damage. Issue 7 (28th October 2014)

• Record Type: Journal Article
• Authors: Baumgart, Bethany R.; Van Vleet, Terry R.; Simic, Damir; Salcedo, Theodora W.; Lentz, Kimberley; Donegan, Michael; Davies, Marc H.; Bunch, Roderick T.; Sanderson, Thomas P.; Lange, Robert W.
• Is Part Of: Journal of applied toxicology. Volume 35:Issue 7(2015)
• Page Start: 791
• Page End: 798
• Publication Date: 2014-10-28
• Subjects: Toxicology -- Periodicals; Industrial toxicology -- Periodicals; Environmentally induced diseases -- Periodicals; Toxicology -- Periodicals; 615.9005
• DOI: 10.1002/jat.3072
• Languages: English
• ISSNs: 0260-437X

Abstract

<abstract abstract-type="main"> <title>Abstract</title> <p>The objective of this study was to evaluate potential protective effects of vehicles containing <sc>d</sc>‐α‐tocopheryl polyethylene glycol 1000 succinate (TPGS), which may impact nonclinical safety assessments of oxidative processes. This was achieved by evaluating plasma, liver and adrenal gland concentrations of <sc>d</sc>‐α‐tocopheryl succinate (TS) and <sc>d</sc>‐α‐tocopherol as well as oxidative status of plasma following oral dosing of TPGS‐containing vehicles, intraperitoneal (IP) dosing of TS or <italic>ex vivo</italic> treatment of blood with H<sub>2</sub>O<sub>2</sub>. Male and female rats were dosed orally with formulations containing 5% or 40% TPGS (70 or 550 mg kg<sup>–1</sup> day<sup>–1</sup> TS, respectively) for 1 week. A control group was dosed orally with polyethylene glycol‐400 (PEG‐400; no vitamin E) and positive control animals received a single 100 mg kg<sup>–1</sup> day<sup>–1</sup> IP injection of TS. Whole blood from untreated animals was treated <italic>ex vivo</italic> with 5 or 50 m<sc>m</sc> H<sub>2</sub>O<sub>2</sub>, with or without TS (0.5, 5, 50 or 500 μ<sc>m</sc>) or ascorbate (1 m<sc>m</sc>), for 1 h. Oral TPGS treatments did not affect <sc>d</sc>‐α‐tocopherol concentrations in plasma or adrenal glands and caused only transient increases in liver. Concentrations of TS in plasma, liver and adrenal glands were undetectable in control animals, but increased in all other groups. Oral administration of TPGS did not reduce plasma lipid peroxidation <italic>in vivo</italic>. Substantially greater TS concentrations used <italic>ex vivo</italic> (100× greater than <italic>in vivo</italic>) were also unable to reduce lipid peroxidation in H<sub>2</sub>O<sub>2</sub>‐treated whole blood. These results provide evidence that administration of oral TPGS vehicles is unlikely to impact nonclinical safety assessments of pharmaceuticals. Copyright © 2014 John Wiley & Sons, Ltd.</p> </abstract>