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.

The acute toxicity and hypokinetic activity induced by menthofuran on the gastrointestinal tract of rodents were investigated in the present study. An absence of acute toxicity was observed. Menthofuran delayed gastric emptying at oral doses of 25, 50, and 100 mg/kg in the experimental model of phenol red, as well as it reduced the intestinal transit at oral doses of 50 and 100 mg/kg. Interestingly, a scopolamine-similar hypokinetic effect was observed for menthofuran. In the experimental model of castor oil-induced intestinal hypermotility, menthofuran (50 and 100 mg/kg) reduced the number of loose stools as observed for the normal group. Additionally, menthofuran induced a marked concentration-dependent relaxation in rat ileum segments precontracted with KCl (EC50 = 0.059 ± 0.008 μg/mL) or carbachol (EC50 = 0.068 ± 0.007 μg/mL). These results suggest the possible decrease of calcium influx underlying the effects of menthofuran on the gastrointestinal tract, which opens the door for further study regarding this potential application for the treatment of gastrointestinal disorders, noting possible limitations of its use due to adverse effects in children.