ANTIANXIETY EFFECT OF ETHYL PYRUVATE IN TYPE 2 DIABETIC RATS

Rajdeep Kaur* and Dr. Silvia Navis

ABSTRACT

Diabetes is associated with several complications like neuropathy, retinopathy, nephropathy, hypertension etc. Apart from all these complications, psychological problems are also associated with diabetes. Patients with diabetes are at greater risk of developing anxiety and this association has impact on the quality of life of the patient. Anxiety itself is a major contributor in the worsening of glycemic control. Diabetic patients experience several stresses which may be due to diseased condition or treatment of disease and these stresses include fear of hypoglycaemia, regular insulin injections, changes in life style, poor glycemic control etc. Ethyl pyruvate (EP) is a lipophilic ester derivative of pyruvate. Pyruvate plays a central role in intermediary metabolism and is the final product of glycolysis and the starting substrate for the tricarboxylic acid (TCA) cycle. Ethyl pyruvate inhibits IDO enzyme (indoleamine 2–3-dioxygenase), an enzyme that induces the catabolism of tryptophan into TRYCATs (tryptophan catabolites along the IDO pathway), such as kynurenin which is a key mediator in the degradation of serotonin. Ethyl pyruvate is a known antioxidant and also known to scavenge the free radicles. Objective: To study the antianxiety effect of the Ethyl pyruvate in type 2 diabetic rats. Materials and methods: Rats were randomly divided into six groups of eight rats each. Type 2 diabetes was induced with the help of high fat diet followed by administration of low dose of the streptozotocin (35 mg/kg) injection. Type 2 diabetes model was validated by estimating the plasma glucose, Plasma triglycerides, plasma cholesterol levels and lipid profile which were estimated with the help of kits. Body weight of rats was measured at 0, 14, 21 and 42 day of the study. Various activity models like elevated plus maze model, light and dark box and open field model were used in the different groups. Drug treatments with ethyl pyruvate through (i.p.) (10 mg/kg, 50 mg/kg and 100 mg/kg) and combination of ethyl pyruvate (50 mg/kg) with the metformin (100 mg/kg) were given for 21 days. Thiobarbituric acid reactive substances (TBARS) and glutathione were estimated in the brain of the normal, type 2 diabetic and drug treated rats at the end of the study. Brain serotonin levels were estimated in the normal, type 2 diabetic and drug treated rats. Results: Ethyl pyruvate (10mg/kg) did not show much significant effect in diabetes induced anxiety. Treatment with Ethyl pyruvate has no significant effect on the body weight of rats. Significant decrease in the glucose, triglycerides, cholesterol and lipid profile of rats was found after the administration of Ethyl pyruvate. Anxiety behaviour and oxidative stress parameters were improved after the treatment with the Ethyl pyruvate. Levels of serotonin was also increased after the treatment with Ethyl pyruvate. Conclusion: Our current preclinical showed that Ethyl pyruvate and its combination with metformin is effective in type 2 diabetes induced anxiety in rat model by improving the glucose levels, cholesterol levels, lipid profile, increasing anti-oxidant enzyme levels and brain serotonin levels. Ethyl pyruvate (10 mg/kg) was not much effective. Further studies are encouraged to identify the mechanisms responsible for anti-anxiety activity.

Keywords: Type 2 diabetes, Anxiety, Serotonin, TBARS.