Effect of rosmarinic acid on insulin sensitivity, glyoxalase system and oxidative events in liver of fructose-fed mice.

Abstract

The study investigates the effects of rosmarinic acid (RA) on insulin sensitivity, protein glycation and oxidative events in fructose-fed mice, a model of insulin resistance (IR). Experiments were performed in four groups of animals administered either fructose diet or starch diet with and without RA administration. Insulin sensitivity indices were computed at the end of the treatment period. Redox homeostasis in liver was determined by assaying lipid peroxidative markers and antioxidants in the liver. Glyoxalase system and protein damage were assessed by assaying aldehydes, glyoxalase I and II, protein carbonyls, total thiols and nitrosothiols. Protein glycation was studied by measuring glycated hemoglobin, fructosamine and advanced glycation end products. Mitochondrial function was assessed by assaying succinate dehydrogenase and calcium ATPase. Fructose administration caused glycation of proteins, changes in metabolic parameters, inactivation of the glyoxalase system and depletion of antioxidants. Oxidative stress and reduced mitochondrial function were observed. Administration of RA to fructose-fed mice mitigated the above alterations. The data suggest that metabolic and redox disturbances in this dietary model of IR could be mitigated by RA. The antioxidant action of RA could be one of the contributing mechanisms for the improvement of insulin sensitivity.