| summary | Dexamethasone (Dex) is a synthetic glucocorticoid drug usually prescribed as anti-inflammatory and immunosuppressant in different medical conditions. Dex is known to cause multiple metabolic side effects, e.g., weight change, hyperglycemia, and osteoporosis, by regulating several metabolic pathways through binding to the glucocorticoid receptor. GRs are expressed in most organ tissues and cell types and regulate multiple downstream signaling pathways in different organs. The prolonged administration of Dex is known to cause muscle atrophy, hemorrhagic lung and liver, and kidney cysts in an animal model due to its nonspecific binding. Herein, we have studied the pathways involved in changes in different organs related side effects in rats after 14 weeks of treatment with Dex using a liquid chromatography-tandem mass spectrometry (LC-MS/MS) based proteomics approach. The animals were treated with 2.5 mg/kg of dex (twice a week), after which various organs (liver, heart, kidney, muscle, and brain) were collected. The Dex-treated animals had reduced weight gain (~ 20%), hyperglycemia, abnormal lipid profile, muscle atrophy, kidney cysts, and lung hemorrhage. The proteomic analysis of the liquid nitrogen snap frozen tissues revealed differential regulation of 190 proteins in the brain (90 up- and 100 down-regulated), 193 proteins in the heart (78 up- and 115 down-regulated), 39 proteins in the muscle (30 up- and 9 down-regulated), 230 protein in the liver (128 up- and 120 down-regulated, and 53 proteins in the kidney (38 up- and 15 down-regulated) between the Dex-treated and control rats. In the brain, cell morphology, nervous system development and function and neurological disease (score = 38), were the main identified pathways, while cellular development, cellular function, and maintenance, connective tissue development and function in heart tissue were most prominent. In addition, nucleic acid metabolism and small molecule biochemical pathways were identified in skeletal muscle and many other pathways in liver and kidney tissues. This study provides comprehensive organ-specific proteomics profiles after prolonged Dex treatment, which may help explain its severe side effect. Manipulation of the different implicated pathways may help control some of these side effects. |
| contributors | Abeer K. Malkawi, Afshan Masood, Zakia Shinwari, Minnie Jacob, Hicham Benabdelkame, Goran Matic, Falah Almuhanna, Majed Dasouki, Ayodele A. Alaiya, Anas M. Abdel Rahman
|
