PA01.72. Evaluation of DB14201 on prevention of development of streptozotocin induced diabetes mellitus in wistar rats

PURPOSE: Study is part of an ongoing reverse pharmacology approach in new drug development for diabetes. It was designed to determine the potential of DB14201 to prevent the development of Streptozotocin induced Diabetes Mellitus in Wistar rats. METHOD: 35 female Wistar rats were randomized and allocated to different groups on the basis of body weight. G1 served as non diabetic control (Negative Control) and G2 served as Diabetic control (Vehicle Control) and received 10 ml/kg of Milli Q water. G3 and G4 were treated with 500mg/kg and 250mg/kg of DB14201 respectively. All the groups were treated orally for 21 days using disposable syringes tipped with an oral gavage needle. At the end of dosing period, hyperglycemia was induced in G2,G3 and G4 rats by intra peritoneal injection of streptozotocin (STZ) 55 mg/kg in citrate buffer (pH 4.5). Fasting blood glucose level was estimated before induction of diabetes and on 2nd & 7th days post induction. All animals were observed daily for mortality and clinical signs of toxicity throughout the experimental period. Body weight of each animal was recorded daily throughout the experimental period. On the 8th day post STZ injection, animals were killed by cervical dislocation. Their pancreatic tissues were quickly removed. Tissues were washed in normal saline and visible clots were removed to minimize blood contamination. Part of the pancreatic tissue was sent for histological evaluation. With second part of tissue, homogenates was prepared and stored at 70 A°C until the determination of biochemical parameters and enzyme activity. RESULT: Findings of this study strongly demonstrate that DB14201 treatment have prominent role in the prevention of STZ induced diabetes mellitus. CONCLUSION: Result clearly indicates the prophylactic as well as therapeutic potential of DB14201 in this experimental model. DB14201 at the dose of 500mg/kg was found to be more promising.