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Review
. 2023 Nov 9;12(11):1987.
doi: 10.3390/antiox12111987.

Tocotrienols Provide Radioprotection to Multiple Organ Systems through Complementary Mechanisms of Antioxidant and Signaling Effects

Stephen A Shrum  1   2 , Ujwani Nukala  1   3 , Shivangi Shrimali  1   3 , Edith Nathalie Pineda  1   3 , Kimberly J Krager  1 , Shraddha Thakkar  1 , Darin E Jones  1 , Rupak Pathak  1 , Philip J Breen  1 , Nukhet Aykin-Burns  1 , Cesar M Compadre  1   2
Affiliations
Review

Tocotrienols Provide Radioprotection to Multiple Organ Systems through Complementary Mechanisms of Antioxidant and Signaling Effects

Stephen A Shrum et al. Antioxidants (Basel). .

Abstract

Tocotrienols have powerful radioprotective properties in multiple organ systems and are promising candidates for development as clinically effective radiation countermeasures. To facilitate their development as clinical radiation countermeasures, it is crucial to understand the mechanisms behind their powerful multi-organ radioprotective properties. In this context, their antioxidant effects are recognized for directly preventing oxidative damage to cellular biomolecules from ionizing radiation. However, there is a growing body of evidence indicating that the radioprotective mechanism of action for tocotrienols extends beyond their antioxidant properties. This raises a new pharmacological paradigm that tocotrienols are uniquely efficacious radioprotectors due to a synergistic combination of antioxidant and other signaling effects. In this review, we have covered the wide range of multi-organ radioprotective effects observed for tocotrienols and the mechanisms underlying it. These radioprotective effects for tocotrienols can be characterized as (1) direct cytoprotective effects, characteristic of the classic antioxidant properties, and (2) other effects that modulate a wide array of critical signaling factors involved in radiation injury.

Keywords: antioxidant; delta-tocotrienol; gamma-tocotrienol; mechanism of action; radiation countermeasures; radiation injury; radioprotection; signaling effects; tocotrienols.

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Conflict of interest statement

The University of Arkansas and Tocol Pharmaceuticals, LLC have applied for patent protection on tocoflexols and other tocotrienol-containing products. A potential royalty stream to Nukhet Aykin-Burns, Philip J. Breen, Cesar M. Compadre, Darin E. Jones, Shraddha Thakkar, and Edith Nathalie Pineda may occur, consistent with the University of Arkansas policy.

Figures

Figure 1
Figure 1
Chemical structures for the tocopherol and tocotrienol isoforms.
Figure 2
Figure 2
Schematic representation of the multi-organ radioprotective effects of tocotrienols, the underlying pharmacological mechanisms of action, and associated signaling pathways. The interdependency of each organ system is emphasized. Created with BioRender.com.
Figure 3
Figure 3
Schematic representation of how tocotrienols protect the hematopoietic system from radiation injury through complimentary actions of antioxidant and signaling effects. Created with BioRender.com.
Figure 4
Figure 4
Schematic representation of how tocotrienols protect the vascular endothelium from radiation injury through complimentary actions of antioxidant and signaling effects. Created with BioRender.com.
See this image and copyright information in PMC

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