الفهرس 
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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
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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.
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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.