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Tempol moderately extends survival in a hSOD1(G93A) ALS rat model by inhibiting neuronal cell loss, oxidative damage and levels of non-native hSOD1(G93A) forms.

Linares, E, Seixas, LV, dos Prazeres, JN, Ladd, FV, Ladd, AA, Coppi, AA and Augusto, O (2013) Tempol moderately extends survival in a hSOD1(G93A) ALS rat model by inhibiting neuronal cell loss, oxidative damage and levels of non-native hSOD1(G93A) forms. PLoS One, 8 (2).

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Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive dysfunction and death of motor neurons by mechanisms that remain unclear. Evidence indicates that oxidative mechanisms contribute to ALS pathology, but classical antioxidants have not performed well in clinical trials. Cyclic nitroxides are an alternative worth exploring because they are multifunctional antioxidants that display low toxicity in vivo. Here, we examine the effects of the cyclic nitroxide tempol (4-hydroxy-2,2,6,6-tetramethyl piperidine-1-oxyl) on ALS onset and progression in transgenic female rats over-expressing the mutant hSOD1(G93A) . Starting at 7 weeks of age, a high dose of tempol (155 mg/day/rat) in the rat´s drinking water had marginal effects on the disease onset but decelerated disease progression and extended survival by 9 days. In addition, tempol protected spinal cord tissues as monitored by the number of neuronal cells, and the reducing capability and levels of carbonylated proteins and non-native hSOD1 forms in spinal cord homogenates. Intraperitoneal tempol (26 mg/rat, 3 times/week) extended survival by 17 days. This group of rats, however, diverted to a decelerated disease progression. Therefore, it was inconclusive whether the higher protective effect of the lower i.p. dose was due to higher tempol bioavailability, decelerated disease development or both. Collectively, the results show that tempol moderately extends the survival of ALS rats while protecting their cellular and molecular structures against damage. Thus, the results provide proof that cyclic nitroxides are alternatives worth to be further tested in animal models of ALS.

Item Type: Article
Authors :
NameEmailORCID
Linares, EUNSPECIFIEDUNSPECIFIED
Seixas, LVUNSPECIFIEDUNSPECIFIED
dos Prazeres, JNUNSPECIFIEDUNSPECIFIED
Ladd, FVUNSPECIFIEDUNSPECIFIED
Ladd, AAUNSPECIFIEDUNSPECIFIED
Coppi, AAa.coppi@surrey.ac.ukUNSPECIFIED
Augusto, OUNSPECIFIEDUNSPECIFIED
Date : 2013
Identification Number : https://doi.org/10.1371/journal.pone.0055868
Uncontrolled Keywords : Amyotrophic Lateral Sclerosis, Animals, Antioxidants, Cyclic N-Oxides, Disease Models, Animal, Disease Progression, Female, Humans, Male, Motor Neurons, Mutation, Neuroprotective Agents, Oxidative Stress, Protein Folding, Rats, Rats, Transgenic, Spin Labels, Spinal Cord, Superoxide Dismutase, Survival Rate
Related URLs :
Depositing User : Symplectic Elements
Date Deposited : 17 May 2017 10:11
Last Modified : 17 May 2017 14:47
URI: http://epubs.surrey.ac.uk/id/eprint/826748

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