Inhibition of oxygen-dependent radiation-induced damage by the nitroxide superoxide dismutase mimic, Tempol

doi:10.1016/0003-9861(91)90442-L

Archives of Biochemistry and Biophysics

Volume 289, Issue 1, 15 August 1991, Pages 62-70

https://doi.org/10.1016/0003-9861(91)90442-L Get rights and content

Abstract

Stable nitroxide radicals have been previously shown to function as superoxide dismutase (SOD)² mimics and to protect mammalian cells against superoxide and hydrogen peroxide-mediated oxidative stress. These unique characteristics suggested that nitroxides, such as 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (Tempol), might protect mammalian cells against ionizing radiation. Treating Chinese hamster cells under aerobic conditions with 5, 10, 50, and 100 mm Tempol 10 min prior to X-rays resulted in radiation protection factors of 1.25, 1.30, 2.1, and 2.5, respectively. However, the reduced form of Tempol afforded no protection. Tempol treatment under hypoxic conditions did not provide radioprotection. Aerobic X-ray protection by Tempol could not be attributed to the induction of intracellular hypoxia, increase in intracellular glutathione, or induction of intracellular SOD mRNA. Tempol thus represents a new class of non-thiol-containing radiation protectors, which may be useful in elucidating the mechanism(s) of radiation-induced cellular damage and may have broad applications in protecting against oxidative stress.

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The nitroxide, Tempol, prevents obesity related changes in mice fed a high fat diet (HFD). The purpose of this study was to gain insight into the mechanisms that result in such changes by Tempol in female C3H mice. Microarray methodology, Western blotting, bile acid analyses, and gut microbiome sequencing were used to identify multiple genes, proteins, bile acids, and bacteria that are regulated by Tempol in female C3H mice on HFD. The effects of antibiotics in combination with Tempol on the gut microflora were also studied. Adipose tissue, from Tempol treated mice, was analyzed using targeted gene microarrays revealing up-regulation of fatty acid metabolism genes (Acadm and Acadl > 4-fold, and Acsm3 and Acsm5 > 10-fold). Gene microarray studies of liver tissue from mice switched from HFD to Tempol HFD showed down-regulation of fatty acid synthesis genes and up-regulation of fatty acid oxidation genes. Analyses of proteins involved in obesity revealed that the expression of aldehyde dehydrogenase 1A1 (ALDH1A1) and fasting induced adipose factor/angiopoietin-like protein 4 (FIAF/ANGPTL4) was altered by Tempol HFD. Bile acid studies revealed increases in cholic acid (CA) and deoxycholic acid (DCA) in both the liver and serum of Tempol treated mice. Tempol HFD effect on the gut microbiome composition showed an increase in the population of Akkermansia muciniphila, a bacterial species known to be associated with a lean, anti-inflammatory phenotype. Antibiotic treatment significantly reduced the total level of bacterial numbers, however, Tempol was still effective in reducing the HFD weight gain. Even after antibiotic treatment Tempol still positively influenced several bacterial species such as as Akkermansia muciniphila and Bilophila wadsworthia. The positive effects of Tempol moderating weight gain in female mice fed a HFD involves changes to the gut microbiome, bile acids composition, and finally to changes in genes and proteins involved in fatty acid metabolism and storage.
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Citation Excerpt :
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²: Abbreviations used: SOD, superoxide dismutase; DF, desferrioxamine; Tempol, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl; DTPA, diethylenetriaminepentaacedic acid; BSO, l-buthionine sulfoximine; Tempol-H, Tempol-hydroxylamine; RT, room temperature; PBS, phosphate-buffered saline; SDS, sodium dodecyl sulfate.

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Inhibition of oxygen-dependent radiation-induced damage by the nitroxide superoxide dismutase mimic, Tempol

Abstract

J. Biol. Chem

Free Radical Biol. Med

Anal. Biochem

Anal. Biochem

Biophys. J

Biochim. Biophys. Acta

J. Biol. Chem

J. Biol. Chem

Free Radic. Biol. Med

Biochem. Biophys. Res. Commun

Int. J. Radiat. Oncol. Biol. Phys

Arch. Biochem. Biophys

Int. J. Radiat. Oncol. Biol. Phys

Pharmacol. Ther

J. Biol. Chem

Arch. Biochem. Biophys

Science

Chemical Protection against Ionizing Radiation

Pure Appl. Chem

Russian Chem. Rev

Bull. Mag. Res

J. Cell. Physiol

Biochemistry

The Chemical Basis of Radiation Biology