Dexamethasone is a synthetic glucocorticoid medication vastly used to treat abnormal immune responses and inflammation. Although the medication is well-established in the medical community, the prolonged treatment with high dosages of dexamethasone may lead to severe adverse effects through mechanisms that are not yet well-known. Lipids are a large class of hydrophobic molecules involved in energy storage, signaling, modulation of gene expression, and membranes. Hence, untargeted lipidomics may help unravel the biochemical alterations following prolonged treatment with high dosages of dexamethasone. We performed comprehensive lipidomic analyses of brain, heart, kidney, liver, and muscle samples obtained from rats that were treated with intramuscular injections of dexamethasone for 14 weeks compared to healthy controls. The employed methodology and statistical analysis showed that phosphatidic acids, glycerophospholipids, plasmalogens, and fatty acids are deeply affected by prolonged use of the medication. Brain tissue was only mildly affected, but skeletal muscle showed a strong accumulation of lipids that may be correlated with alterations in the energy metabolism, myopathy, and oxidative processes. This work provides new insights into the mechanisms of action and adverse effects for one of the most commonly prescribed class of drugs in the world.
Keywords: dexamethasone; glucocorticoid; lipidomics; mass spectrometry; muscle; phosphatidic acids; plasmalogens; tissue.