Beneficial effect of succinic acid monoethyl ester on erythrocyte membrane bound enzymes and antioxidant status in streptozotocin-nicotinamide induced type 2 diabetes

Chem Biol Interact. 2007 Aug 15;169(1):15-24. doi: 10.1016/j.cbi.2007.04.010. Epub 2007 May 4.


Succinic acid monoethyl ester (EMS) was recently proposed as an insulinotropic agent for the treatment of non-insulin dependent diabetes mellitus. In the present study the effect of EMS and metformin on erythrocyte membrane bound enzymes and antioxidants activity in plasma and erythrocytes of streptozotocin-nicotinamide induced type 2 diabeteic model was investigated. Succinic acid monoethyl ester was administered intraperitonially for 30 days to control and diabetic rats. The effect of EMS on glucose, insulin, hemoglobin, glycosylated hemoglobin, TBARS, hydroperoxide, superoxide dismutase (SOD), catalase (CAT), glutathione peroxide (Gpx), glutathione-S-transferase (GST), vitamins C and E, reduced glutathione (GSH) and membrane bound enzymes were studied. The effect of EMS was compared with metformin, a reference drug. The levels of glucose, glycosylated hemoglobin, TBARS, hyderoperoxide, and vitamin E were increased significantly whereas the level of insulin and hemoglobin, as well as antioxidants (SOD, CAT, Gpx, GST, vitamin C and GSH) membrane bound total ATPase, Na(+)/K(+)-ATPase, Ca(2+)-ATPase and Mg(2+)-ATPase were decreased significantly in streptozotocin-nicotinamide diabetic rats. Administration of EMS to diabetic rats showed a decrease in the levels of glucose, glycosylated hemoglobin, lipid peroxidation markers and vitamin E. In addition the levels of insulin, hemoglobin, enzymic antioxidants, vitamin C, and GSH and the activities of membrane bound enzymes also were increased in EMS and metformin treated diabetic rats. The present study indicates that the EMS possesses a significant beneficial effect on erythrocyte membrane bound enzymes and antioxidants defense system in addition to its antidiabetic effect.

MeSH terms

  • Adenosine Triphosphatases / metabolism
  • Animals
  • Antioxidants / metabolism*
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / metabolism*
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Type 2 / chemically induced
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diabetes Mellitus, Type 2 / pathology
  • Erythrocyte Membrane / drug effects*
  • Erythrocyte Membrane / enzymology
  • Glycosylation
  • Hemoglobins / metabolism
  • Hydrogen Peroxide / blood
  • Insulin / blood
  • Lipid Peroxidation
  • Male
  • Niacinamide / pharmacology
  • Rats
  • Rats, Wistar
  • Streptozocin / pharmacology
  • Succinates / pharmacology*
  • Thiobarbituric Acid Reactive Substances / metabolism


  • Antioxidants
  • Blood Glucose
  • Hemoglobins
  • Insulin
  • Succinates
  • Thiobarbituric Acid Reactive Substances
  • monoethyl succinate
  • Niacinamide
  • Streptozocin
  • Hydrogen Peroxide
  • Adenosine Triphosphatases