PA01.79. Effect of DB 14201 on experimentally induced uncontrolled Diabetes 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 effect of DB14201 on experimentally induced uncontrolled diabetes in male Wistar rats. METHOD: The rats were divided in eight groups namely, (G1) Non diabetic control, (G2) diabetic control, (G3) test item 250mg/kg, (G4) test item 500 mg/kg, (G5) Metformin 500 mg/kg, (G6) Metformin 250 mg/kg, (G7) combination of T.I (250 mg/kg) and Metformin (250mg/kg) and (G8) combination of T.I (500 mg/kg) and Metformin (250mg/kg). All groups had 10 animals each except G1, the non diabetic vehicle control group, which had 5 animals. Hyperglycemia was induced in the all the animals (except G1) by intraperitoneal injection of STZ at the dose of 65mg/kg. Seven days post STZ induction; all the groups were treated orally with respective study materials for 21 days using disposable syringes tipped with an oral gavage needle. Blood glucose level, body weight, toxic signs and survival rate of animal was recorded throughout the dosing period. RESULT: Amongst all the DB14201 treated groups, G& i.e, combination of Metformin 250mg/kg and DB14201 250mg/kg showed maximum efficacy in lowering blood glucose level. However in the same group mortality rate was high. The body weight change throughout the study was not significant (<20%) in all the groups, which nullifies any drug related toxicity. Remarkable elevation of triglyceride levels in the diabetes induced groups give the evidence of uncontrolled diabetes. G3 i.e. DB14201 250mg/kg showed maximum survival rate at the end of the study. The relative survival percentage in this group was 150, which is the highest among the treatment groups. CONCLUSION: The finding of this study indicates that the test item DB14201 (250 mg/kg) is could be highly effective in terminal stage diabetes in increasing the survival rate.