Introduction and objective: Advances in omics sciences, including genomics, proteomics, and metabolomics, have transformed biomedical research by enabling multi-layered profiling of biological systems. Within this framework, the present study applied advanced proteomic approaches to investigate tissue-specific responses to experimental interventions, focusing on fluorinecontaining drug administration and selenium-based dietary supplementation. The main aim was to elucidate molecular mechanisms underlying these interventions and assess the potential of proteomic signatures for biomarker discovery. Materials and methods: Experimental models included Wistar rats exposed to cinacalcet, a fluorinated pharmaceutical, and lambs supplemented with selenium compounds combined with other nutrients. Liver, brain, and cardiac tissues underwent highresolution LC-MS/MS analysis under a label-free quantification workflow. Data were processed with MaxQuant and Perseus for statistical evaluation, while functional annotation and protein–protein interaction analyses were performed using the STRING database to identify key pathways and interaction clusters. Results: Proteomic profiling identified thousands of proteins with distinct alterations across tissues. Cinacalcet induced pronounced changes in liver proteins related to xenobiotic metabolism, lipid regulation, ion transport, and inflammation, while brain analysis revealed alterations in chromatin-associated proteins with potential roles in cognitive regulation. Selenium supplementation modulated protein expression in cardiac tissue, particularly in proteins linked to cytoskeletal organisation, adhesion, and muscle development. Protein–protein interaction analysis revealed distinct functional clusters reflecting coordinated molecular responses. Conclusions: This study highlights the value of proteomics in elucidating tissue-specific adaptations to pharmacological and nutritional interventions. Integration with other omics offers powerful opportunities for biomarker discovery, drug safety assessment, and precision medicine.

proteomics, label-free quantification, protein–protein interactions, drug safety, omics sciences