Nutritional Intervention with Selenium-Rich Rice Mitigates Arsenic-Induced Liver and Kidney Toxicity in Mice

Chronic exposure to arsenic, a prevalent toxic metalloid, is a major public health concern. This study is aimed at investigating whether dietary intervention with selenium-enriched rice could effectively mitigate chronic arsenic-induced hepatotoxicity and nephrotoxicity in mice and at comparing its efficacy to an inorganic selenium-fortified diet. Over 18 weeks, seven experimental groups were evaluated for body/organ weights, selenium/arsenic accumulation, histopathological changes, oxidative stress markers, molecular mechanisms, and metabolomics alterations in the liver and kidneys. Arsenic exposure reduced body weight, increased organ weight, caused significant liver and kidney damage, and decreased antioxidant enzyme activity. Conversely, both selenium diets improved body weight, enhanced antioxidant activity, and mitigated oxidative stress and inflammation by upregulating Nrf2, SOD1, SOD2, GPX1, GPX2, CAT, MT1, and MT2 while downregulating Tnf-α. Crucially, selenium-enriched rice demonstrated superior efficacy compared to inorganic selenium due to its enhanced bioavailability, resulting in a greater reduction of arsenic accumulation and improved health indicators. Metabolomics analysis revealed arsenic-induced dysregulation of 325 and 441 metabolites in the liver and kidneys, respectively, affecting phosphatidylcholine, spermidine, glutathione, and glycerophospholipid-related pathways. Selenium supplementation partially restored these metabolic imbalances. Organ-specific responses highlighted the liver's role in arginine/proline metabolism and the kidneys' vulnerability to oxidative stress. These findings underscore the protective role of selenium-enriched rice in combating arsenic toxicity through enhanced antioxidant defenses and detoxification pathways, suggesting it as a promising dietary intervention for arsenic-exposed populations.