Selenium Supplementation Mitigates Copper-Induced Systemic Toxicity via Transcriptomic Reprogramming and Redox...

Area of Science:

• Toxicology
• Nutritional Biochemistry
• Genomics

Background:

• Copper is essential but toxic in excess, causing oxidative stress and organ damage.
• Chronic copper accumulation disrupts physiological functions, leading to anemia and immunosuppression.
• Selenium is a vital trace element with antioxidant properties, potentially mitigating heavy metal toxicity.

Purpose of the Study:

• To investigate the protective effects of selenium-enriched rice against chronic copper toxicity in a mouse model.
• To elucidate the molecular mechanisms underlying selenium's protective action against copper-induced hepatorenal damage.
• To evaluate the impact of selenium supplementation on oxidative stress, gene expression, and overall health in copper-exposed mice.

Main Methods:

• Forty-eight male mice were divided into four groups: Control, Copper-300 (Cu300), Cu300 + Selenium-enriched rice, and Cu300 + inorganic selenium (iSe).
• Mice were treated for 180 days, followed by analysis of body weight, organ pathology, copper deposition, blood counts, oxidative stress markers, and gene expression.
• Histopathological and transcriptomic profiling were employed to assess cellular damage and molecular responses.

Main Results:

• Copper exposure induced reduced body weight, hepatomegaly, nephritis, elevated copper deposition, oxidative stress, anemia, and immunosuppression.
• Selenium supplementation significantly mitigated copper toxicity, reducing copper accumulation and restoring antioxidant balance.
• Histopathology showed selenium attenuated copper-induced hepatic and renal tissue damage; transcriptomics revealed selenium reversed copper-related gene expression changes, upregulating protective genes and downregulating stress-related genes.

Conclusions:

• Selenium-enriched rice effectively protects against chronic copper toxicity by restoring mitochondrial function, reducing ER stress and apoptosis, enhancing antioxidant pathways, and modulating immune responses.
• Selenium supplementation demonstrates potent hepatorenal protective effects against copper-induced damage.
• Selenium-enriched rice represents a promising nutritional strategy for managing copper toxicity and maintaining organ health.