Impact of gliclazide and selenium co-treatment on depression in a diabetic rat model

Objectives: Insulin deficiency, insulin resistance, and chronic hyperglycaemia impair neurogenesis and neurotransmitter levels and activate the hypothalamic-pituitary-adrenal axis, leading to oxidative stress and reduced serotonin, resulting in depression. Depression and type 2 diabetes mellitus are comorbid conditions, with each increasing the risk of the other. This study evaluates the effects of gliclazide and its combination with selenium on reserpine-induced depression in diabetic rats. Materials and Methods: Using a fructose-fed-alloxan model, diabetes was induced in Wistar rats, followed by reserpine (0.2 mg/kg/day, i.p.) for 14 days to induce depression. The treatment groups received gliclazide (10 mg/kg/day, p.o.) or gliclazide with selenium (0.2 mg/kg, p.o.) along with reserpine. Effectiveness was measured using the open field test (OFT), tail suspension test (TST), sucrose preference test (SPT) and oxidative stress parameters. Statistical significance was analysed using one-way analysis of variance followed by Dunnett’s test. Results: Gliclazide and its combination with selenium significantly alleviated reserpine-induced depression by increased rearing and crossing in OFT, decreased immobility time in TST, increased sucrose consumption in SPT and reduced oxidative stress in diabetic rats, decreased malondialdehyde levels and increased superoxide dismutase and glutathione levels. Conclusion: The study concludes that the combination of gliclazide with selenium offers protective effects and may benefit patients already using gliclazide as an oral hypoglycaemic agent.