1 Department of Chemistry and Biochemistry, Concordia University, 7141 Sherbrook Street West, Montréal, QC H4B 1R6, Canada.
2 Department of Comparative Medicine, King Faisal Specialist Hospital and Research Center (KFSHRC), Riyadh 11461, Saudi Arabia.
3 Proteomics Resource Unit, Obesity Research Center, College of Medicine, King Saud University, P.O. Box 2925 (98), Riyadh 11461, Saudi Arabia.
4 Stem Cell & Tissue Re-Engineering Program, King Faisal Specialist Hospital and Research Center (KFSHRC), Riyadh 11461, Saudi Arabia.
5 Department of Genetics, King Faisal Specialist Hospital and Research Center (KFSHRC), Riyadh 11461, Saudi Arabia.
6 College of Public Health, Medical, and Veterinary Sciences/Molecular & Cell Biology, James Cook University, Townsville, QLD 4811, Australia.
7 Department of Genetics, King Faisal Specialist Hospital and Research Center (KFSHRC), Riyadh 11461, Saudi Arabia. aabdelrahman46@kfshrc.edu.sa.
8 College of Medicine, Al Faisal University, Riyadh 11533, Saudi Arabia. aabdelrahman46@kfshrc.edu.sa.
9 Department of Chemistry, Memorial University of Newfoundland, St. John's, NL A1B 3X7, Canada. aabdelrahman46@kfshrc.edu.sa.

Prolonged dexamethasone (Dex) administration leads to serious adverse and decrease brain and heart size, muscular atrophy, hemorrhagic liver, and presence of kidney cysts. Herein, we used an untargeted proteomic approach using liquid chromatography-tandem mass spectrometry (LC-MS/MS) for simultaneous identification of changes in proteomes of the major organs in Sprague-Dawley (SD rats post Dex treatment. The comparative and quantitative proteomic analysis of the brain, heart, muscle, liver, and kidney tissues revealed differential expression of proteins (n = 190, 193, 39, 230, and 53, respectively) between Dex-treated and control rats. Functional network analysis using ingenuity pathway analysis (IPA revealed significant differences in regulation of metabolic pathways within the morphologically changed organs that related to: (i) brain-cell morphology, nervous system development, and function and neurological disease; (ii) heart-cellular development, cellular function and maintenance, connective tissue development and function; (iii) skeletal muscle-nucleic acid metabolism, and small molecule biochemical pathways; (iv) liver-lipid metabolism, small molecular biochemistry, and nucleic acid metabolism; and (v) kidney-drug metabolism, organism injury and abnormalities, and renal damage. Our study provides a comprehensive description of the organ-specific proteomic profilesand differentially altered biochemical pathways, after prolonged Dex treatement to understand the molecular basis for development of side effects.