الفهرس | Only 14 pages are availabe for public view |
Abstract The goal of the present investigation was to study the effect of the potent antioxidant; astaxanthin on glycemic state, cognitive brain function and hippocampus DNA in type 2 diabetic male rats and the possible underlying mechanisms. To achieve this goal, 90 adult male albino rats divided into five groups, 18 rats each, were used: non-diabetic, diabetic- non treated, diabetic metformin -treated, diabetic astaxanthin-treated and diabetic combined metformin and astaxanthin treated groups. At the end of the experimental period, tests for cognitive brain functions: MWM, NOR and Y-maze were done. Fasting retro-orbital blood samples were taken from rats and used for assessment of glycaemic state, lipid profile, oxidative stress and inflammatory state. On the next day, animals were killed by cervical elongation and dislocation and brain was sliced into 2 halves for exposure of hippocampus. Right hippocampus was excised and preserved at -80 degree for DNA extraction, evaluation of the electrophoretic pattern of RNA and detection of apoptotic bands. Tissue of left hippocampus was prepared for H & E staining then examined under a light microscope. The intensity of expression of phosphorylated tau was measured by immunohistochemistry technique using anti-phospho- tau monoclonal antibody as a key step in the pathogenesis of neurodegeneration with calculation of immunoreactive score (IRS) for each group. In the present investigation, feeding rats with HFD for 2 weeks and low dose of STZ (35mg/kg) produced a significant decline of cognitive brain functions of diabetic non-treated group when compared to the corresponding Summary 139 values of non-diabetic group. This was associated with significant increase in fasting serum glucose, HbA1c, HOMA IR, TC, TG, LDL-c, MDA, IL-6, phosphorylated tau, DNA fragmentation and degeneration associated with significant decreased in serum insulin, HDL, TAC and intact DNA when compared to the corresponding values of non-diabetic group. In the present investigation, oral administration of astaxanthin as monotherapy improved cognitive brain functions when compared to the corresponding values of diabetic–non treated group. At the molecular level, astaxanthin treated group showed a significant elevation of optical density of intact hippocampus DNA with a significant reduction in hippocampus RNA and DNA fragmentation when compared to diabetic non-treated group. Improvement in cognitive brain functions with astaxanthin can be explained by the anti-diabetic activity proved by significantly deceased fasting serum glucose, Hb A1C and HOMA-IR index, while serum insulin was significantly higher. This anti-diabetic activity was associated with a significant improvement in the lipid profile and significant decrease in phosphorylated tau can be attributed to its antioxidant and anti-inflammatory effects. In the present investigation, treatment of diabetic rats with metformin (200 mg/kg/day) for 4 weeks, revealed improvement in cognitive brain functions, significantly increased optical density of electrophoretic hippocampal RNA, and intact hippocampal DNA associated with a significant decline of the apoptotic pattern of DNA fragmentation affecting hippocampal tissue at the molecular level in type 2 diabetic rats which can be explained by the significant decrease in phosphorylated tau, the improvement of glycaemic state in the form of statistically significant reduction of fasting serum glucose, HbA1c, HOMAIR while serum insulin was significantly higher. Summary 140 This was associated with improvement in the lipid profile in the form of significant reduction of TC, TG, LDL-c; while HDL-c was significantly higher in diabetic metformin-treated group when compared to the corresponding values of diabetic –non treated group. Metformin treatment of type II diabetic rats was proved to have anti-inflammatory and antioxidant effect by the significant decrease in IL-6 and MDA levels with a significant increase in TAC when compared with the diabetic non-treated group. The present investigation demonstrated that the combination of Astaxanthin (1 mg/kg) and MET (200 mg/kg) for 4 weeks, revealed statistical significant decrease in of fasting serum glucose, HbA1c, HOMA-IR, TC, TG, LDL-c, MDA and IL-6; while HDL-c, TAC were significantly higher when compared to the corresponding values of DNT, D+Met and D+Asx groups. This was associated with significant improvement in cognitive brain functions, significantly increased optical density of electrophoretic hippocampal RNA, and intact hippocampal DNA associated with a significant decline of the apoptotic pattern of DNA fragmentation affecting hippocampal tissue at the molecular level when compared to the corresponding values of DNT, D+Met and D+Asx groups. The improvement in all previously investigated parameters can be explained on the basis of combination of hypoglycemic, antioxidant and antiinflammatory effects of metformin in addition to the hypoglycemic, antioxidant and anti-inflammatory effects of astaxanthin. |