Leucine supplementation affects metabolic parameters and redox balance in a Cushing’s syndrome model in rats

Abstract

Cushing’s syndrome (CS) is a disease that promotes several metabolic disorders and redox imbalance. Thus, in this paper, we standardized an experimental model of CS in rats and evaluated the effects of supplementation with leucine (LEU). Rats were injected intraperitoneally with dexamethasone (0.4; 0.6; 0.8; and 1.0 mg/kg) 4x/wk. for four weeks. The effects of LEU supplementation (0.5, 1.0, and 1.5% v/v in water to drink) were also evaluated. In vitro and in vivo evaluation of metabolic and redox parameters by biochemical and molecular assays defined the severity of the disease. Dexamethasone 1.0 mg/kg promoted the most severe symptoms of CS: such as weight loss, adiposity increase, glucose intolerance, and insulin resistance, as well as an increase in oxidative status in the liver. Moreover, LEU promoted a pattern of mixed dyslipidemia, adiposity increase, and raised serum levels of aspartate aminotransferase (AST). Likewise, it increased myeloperoxidase (MPO) activities and decreased the CAT mRNA in the liver, while it reduced NADPH oxidase (NOX) mRNA. Supplementation with LEU worsens metabolic status and liver damage in rats with CS without an evident antioxidant potential, suggesting that the administration of LEU represents a risky strategy to patients suffering from CS.