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Effect of A-lipoic acid on gliclazideinduced hypoglycemia/ antihyperglycemia in normal/alloxaninduced diabetic rats

S Satyanarayana, K Eswar Kumar and J Raja Sekhar

Background: Gliclazide is a widely used drug for the treatment of Type 2 diabetes. α-lipoic acid is an ingredient of antioxidant formulations used as health supplements along with antidiabetic drugs. The role of α-lipoic acid on the hypoglycemic activity of gliclazide is not currently known. Objective: The objective of this study was to examine the effect of oral administration of α-lipoic acid on blood glucose and investigate its potential influence on gliclazide-induced hypoglycemia in normal and diabetic rats. Materials & methods: Albino rats of either sex were divided into three groups of six each and were fasted for 18 h prior to the experiment with water ad libitum – the rats continued to fast throughout. Groups I/II/III were treated with α-lipoic acid at half the therapeutic dose (½TD)/TD/twice TD of humans extended to 200 g rat, respectively. Later in the study, group II rats were treated with gliclazide TD (1.44 mg/200 g body weight of rat)/α-lipoic acid TD + gliclazide TD with a washout period of 1 week between treatments. Diabetes was induced by alloxan monohydrate 100–150 mg/kg body weight intraperitoneally. A group of six rats showing fasting blood glucose levels above 200 mg/dl were selected for the study. Rats were treated with α-lipoic acid TD, gliclazide TD and α-lipoic acid TD + gliclazide TD with a washout period of 1 week between treatments. Blood samples were collected from the retro-orbital plexus at 0, 1, 2, 3, 4, 6, 8, 10 and 12 h and were analyzed for blood glucose by the Glucose Oxidase/Peroxidase method. Results: α-lipoic acid TD produced hypoglycemia with peak effect at 6 h in normal and diabetic rats. The percentage blood sugar reduction was greater in diabetic than normal rats. Gliclazide TD produced hypoglycemia with peak effects at 2 and 8 h in normal and diabetic rats. In combination, α-lipoic acid TD enhanced and significantly prolonged the glucose-lowering effect of gliclazide TD at 1 and 6 h in normal rats and 2, 6 and 8 h in diabetic rats without hypoglycemic convulsions. Conclusion: Thus, it can be concluded that the use of lipoic acid in supplemental formulations in conjunction with gliclazide may be safe in diabetic patients. However, further studies are warranted.