Abstract:
Introduction: Selenium is a fundamental micronutrient required for biosynthesizing glutathione
peroxidase 4, a key antioxidant enzyme responsible for maintaining cellular redox homeostasis. Its
primary biochemical function is reducing lipid hydroperoxides to alcohols, effectively inhibiting
ferroptosis - a form of regulated cell death characterized by iron-dependent lipid peroxidation. In tissue
engineering, the viability of a graft is critically challenged by ischemia-reperfusion injury, where
reintroduction of oxygen generates high levels of reactive oxygen species. This study evaluates the
potential of the selenium-glutathione peroxidase 4 axis in protecting healthy transplanted tissues while
simultaneously targeting residual malignant cells.
Materials and Methods: A systematic review of molecular research was conducted using databases
such as PubMed, ScienceDirect, Google Scholar and Wiley Online Library (2015–2026). The analysis
focused on the metabolic pathways of selenoproteins and their role in preventing membrane damage.
Data from the Saccharomyces cerevisiae eukaryotic model were utilized to assess the dose-dependent
effects of selenium genomic integrity and mitochondrial respiration. Additionally, we reviewed current
evidence regarding the autophagy-mediated turnover of GPX4 and the impact of selenium availability
on enzymatic stability.
Results: The data demonstrate a clear hormetic effect of selenium compounds, defined as a dual-phase
response where physiological doses provide cellular protection while supra-optimal concentrations
induce toxicity. At physiological levels, selenium upregulates glutathione peroxidase 4 activity,
significantly reducing malondialdehyde levels - a definitive biomarker of oxidative damage -thereby
enhancing graft survival. Conversely, excessive inorganic sodium selenite exhibits pro-oxidant
properties by interacting with thioredoxin reductase 1. This interaction converts the enzyme into a proapoptotic inducer, triggering lethal oxidative stress specifically in malignant cells. By utilizing
biomimetic scaffolds for controlled delivery of selenium, it is possible to maintain an antioxidant
environment for tissue regeneration while inducing selective ferroptotic death in cancer cell
populations.
Conclusions: The selenium-glutathione peroxidase 4 pathway is a critical target for optimizing
outcomes in regenerative medicine and oncology. Modulating this axis provides a dual-action strategy:
stabilizing cellular integrity of engineered grafts and establishing a metabolic safety net against tumor
recurrence. Integrating selenium-enriched biomaterials represents a significant advancement in the
development of safer and more effective protocols for tissue transplantation and post-oncological
recovery.
