Investigation of effect of metformin on diabetic neuropathy and cognitive functions in streptozotocin induced diabetic rat model

Background/Aim: Neurodegeneration is one of the most important complications of diabetes. The exact mechanisms underlying neurodegeneration related to diabetic complications such as cognitive deficits and peripheral neuropathy are not clarified yet. Streptozotocin is a naturally occurring chemical that is particularly toxic to the insülin producing beta cells of the pancreas in mammals. In this study, we aimed to investigate the possible neuroprotective effects of metformin (MET) in diabetic rats. Materials and Methods: Thirty male Wistar albino rats were randomly divided into tree groups: Control group, STZ group, STZ+MET group. STZ (55 mg /kg) was administered intraperitoneally to create diabetes. Metformin (500 mg/kg) was administered by oral gavage every day for six weeks. Hot-plate analgesia test was performed to rats six weeks after. Morris Water Maze Test was used to for the assessment of cognitive function in the last week of the test process. Sciatic nerve and the hippocampus tissue was evaluated histologically. Markers of oxidative stress MDA, SOD, GSH , TAS , TOS levels were measured in brain tissue. Results: The average blood glucose levels based on the six weeks groups; Control 130±29 mg/dl, STZ 486±120 mg/dl and STZ+MET 256±36 mg/dl. According to the findings of Hot plate in which periphiral neuropathy was evaluated, while the period of aching in the diabetes group has gotten longer, that the period aching in the metformin group has shortened (p<0.05). It could be seen in the MWM results that the distance the rats in the STZ group covered in order to find the platform is longer and more complicated compared to the rats in the control group and the results of the STZ+MET group are similar to the ones in the control group. The percentage of degenerated neurons that were evaluated during the histological examinations on the hippocampus tissues are as follows; Control group %15,6, STZ % 45,6 and STZ+MET group %36,5. that the degeneration in the STZ group compared to the control group was statistically significant. The recovery in the STZ+MET group were better compared to the control group (p <0.001). The sciatic nerve was scored histopathological , it was observed that there is a significant increase in the STZ group compared to the control group and a significant decrease in the STZ+MET group compared to the STZ group (p<0.001). According to the oxidative stress and antioxidant analysis results conducted on the brain tissue, STZ group compared to the control group decrease in GSH and TAS findings; MDA, TOS, SOD there were significant increases in findings. STZ + MET group compered to STZ group; There was a significant the rise in the TAS, significant decrease in SOD and MDA findings (p<0.05). Conclusions: In this study, ıt was shown to improve that metformin, structural changes in the sciatic nerve, which reduces the number of degenerated neurons in the hippocampus and due to developing cognitive function impairment in diabetic rats. Key words: Cognitive function, Diabetes Mellitus, Diabetic neuropathy, Metformin, Streptozotocin