INSULIN AND NATURAL HONEY CHANGES HIPPOCAMPAL BCL-2 FAMILY GENE EXPRESSION, SUPEROXIDE DISMUTASE ACTIVITY, AND PASSIVE AVOIDANCE MEMORY IN STREPTOZOTOCIN-INDUCED DIABETIC RATS
Rozita Ghavaminia, Davood Sohrabi, Mitra Arianmanesh, Mohsen Alipour and Iraj Jafari Anarkooli*
The present study was conducted to investigate the effects of insulin and honey on passive avoidance memory, expression of the Bcl-2 family of genes involved in apoptosis and the antioxidant activity of superoxide dismutase (SOD) in the hippocampus of streptozotocin (STZ)-induced diabetic male rats. The present study was conducted on 48 male Wistar rats in eight groups (six rats per group) as follows: healthy and diabetic rats treated with honey alone, insulin alone, both insulin and honey, or untreated. Diabetes was induced by injection of STZ (IP, 60 mg/kg). Three days after diabetes induction, the honey groups were treated by intraperitoneal injection with a 5 mg/kg dose of honey daily. The insulin groups received a daily subcutaneous injection of 2–3 U/kg doses of insulin, and the insulin + honey groups received a combination of the above two treatments at the same dosages. Control groups received normal saline. After four weeks of treatment, passive avoidance learning was assessed using a shuttle box apparatus and 24 hours later, the animals’ memory was tested. The rats were then euthanized and their hippocampi were removed and Bcl-2 and Bax mRNA levels were assessed via semi-quantitative RT-PCR. SOD activity was assessed with a Randox SOD kit. The results showed that treatment of diabetic rats with insulin or honey separately and in combination led to increased learning and improved passive avoidance memory, reduced expression of Bax, increased expression of Bcl-2, increased Bcl-2/Bax ratio and increased SOD activity in the hippocampus region. It appears that treatment of these rats with insulin and honey separately or in combination can prevent apoptosis in the hippocampal region by reducing the expression of pro-apoptotic Bax and increasing the expression of anti-apoptotic Bcl-2, as well as by increasing SOD activity. Through inhibition of apoptosis, this treatment can potentially reduce learning and memory deficiencies caused by hippocampal damage in these rats.
Keywords: Diabetes, insulin, honey, hippocampus, apoptosis, Passive-avoidance learning, Bax, Bcl-2, superoxide dismutase
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