*Diabetic nephropathy is a common complication of diabetes mellitus and one of the major etiologies of end-stage renal disease. Specific therapeutic interventions are necessary to treat such complications. The present study was designed to investigate the metabolomic changes induced by thymoquinone for the treatment of diabetic nephropathy, using a rodent model. Rats were divided into three different groups (n = 6 each): control, diabetic, and thymoquinone- treated diabetic groups. Metabolites in serum samples were analyzed via gas chromatography-mass spectrometry. Multiple changes were observed, including those related to the metabolism of amino acids and fatty acids. The correlation analysis suggested that treatment with thymoquinone led to the reversal of diabetic nephropathy that was associated with modulations in the metabolism and proteolysis of amino acids, fatty acids, glycerol phospholipids, and organic acids. In addition, we explored the mechanisms linking the metabolic profiling of diabetic nephropathy, with a particular emphasis on the potential roles of increased reactive oxygen species production and mitochondrial dysfunctions. Our findings demonstrated that metabolomic profiling provided significant insights-into the basic mechanisms of diabetic nephropathy and the therapeutic effects of thymoquinone.
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