Effect of l-carnitine alone and in combination with metformin on the behavioral and biochemical alterations induced by streptozotocin in Wistar rats

The present study was designed to compare the effect of l-carnitine alone and in combination with metformin on the behavioral and biochemical alterations of streptozotocin (STZ) induced diabetic rats.

Male Wistar rats were used. Control rats received saline. Diabetes was induced by the single intraperitoneal injection of STZ (45 mg/kg). Diabetic rats received insulin (1 IU sc/day), metformin (10 mg/kg/day p.o.) alone, l-carnitine (75 mg/kg/day, i.p.) alone, and a combination of l-carnitine (75 mg/kg/day) + metformin (10 mg/kg/day) daily for 14 days. Rats with blood glucose (BGL) > 200 mg/dl were considered diabetics. On the 14th day, 1 h after the drug administration, blood samples were collected and glucose, nitrite, and malondialdehyde (MDA) assays were performed. Further, the locomotor activity was determined using an open field test (OFT), and depression-related behavior was determined using a tail suspension test (TST) and forced swim test (FST).

Combined treatment of l-carnitine and metformin significantly decreased the blood glucose level of diabetic rats at day 14 and significantly decreased the plasma nitrite level and plasma MDA level of diabetic rats as compared to metformin-alone and l-carnitine-alone-treated diabetic rats. Combined treatment of l-carnitine and metformin significantly decreased the number of squares crossed in OFT as compared to l-carnitine-alone-treated diabetic rats and significantly increased the time spent at the center of the open field as compared to untreated diabetic rats and metformin-alone and l-carnitine-alone-treated diabetic rats. Besides this, the combined therapy of l-carnitine and metformin further significantly decreased the time spent at the periphery of the open field as compared to the untreated diabetic rats and metformin-alone-treated diabetic rats. Combined treatment of l-carnitine and metformin significantly decreased the number of squares crossed in OFT as compared to l-carnitine-alone-treated diabetic rats and significantly increased the time spent at the center of the open field as compared to untreated diabetic rats and metformin-alone and l-carnitine-alone-treated diabetic rats. Besides this, the combined therapy of l-carnitine and metformin further significantly decreased the time spent at the periphery of the open field as compared to the untreated diabetic rats and metformin-alone-treated diabetic rats. In TST and FST, combined therapy further decreased the immobility period of diabetic rats as compared to metformin-alone-treated diabetic rats.

In conclusion, the study demonstrated that the addition of l-carnitine enhanced the therapeutic effects of metformin, improving glucose control, reducing depressive behaviors, and ameliorating lipid peroxidation. These findings suggested the beneficial effect of combined therapy over the metformin or l-carnitine-alone treatment.