High blood glucose levels induce metabolic disorders that initiate a sequence of events including renal, arterial, cardiac and retinal disorders. Diabetes mellitus increases oxidative stress in tissues of animals including humans. The resulting oxidative stress might play role in the development of diabetic complications.
In the present study, 36 male Wistar rats (250-300g) were divided into 5 groups as Control (n=6), Diabetic (n=7), Diabetic + Vit C (n=7), Diabetic + & / #945 / -Lipoic acid (n=6) and Diabetic + Combination of Vit C and & / #945 / -Lipoic acid (n=10).
From the livers of all groups cytoplasmic and microsomal membrane fractions were prepared from liver and antioxidant enzymes namely, superoxide dismutase, glutathione peroxidase, catalase and glutathione S-transferase activities were measured. Microsomal lipid peroxidation, total lipid, total protein, reduced glutathione levels of each group was determined and compared. Microsomal fractions were also analyzed by FT-IR spectroscopy.
The total protein levels of diabetic rats were found to be decreased significantly (p< / 0.05) compared to controls and the & / #945 / -lipoic acid and vitamin C supplemented groups tend to compensate the decreased levels of total proteins. Decreased catalase activity in diabetic group compared to control was restored by & / #945 / -lipoic acid, vitamin C treatment and/or combination of both. Increased glutathione peroxidase activity was decreased to control levels by the treatement of both & / #945 / -lipoic acid and vitamin C. Superoxide dismutase activities of diabetic rats were increased (p< / 0.05) compared to control group. Whereas glutathione S-transferase activities though showed some fluctuations, the results were not statistically significant. Total glutathione levels decreased in all groups significantly (p< / 0.0.5) compared to control group but any of the agent failed to compensate the reduced levels of glutathione. As an index of lipid peroxidation, TBA-reactivity (MDA) levels increased significantly in all diabetic groups and only combination group&rsquo / s TBARS levels decreased significantly compared to diabetic group.
FT-IR study of rat liver microsomal membranes was carried out in order to understand the effects of diabetes on membrane order, dynamics and lipid peroxidation status.
For this purpose CH2 symmetric wavenumber, CH2 antisymmetric bandwidth, =CH olefinic band area were compared. In temperature dependent FT-IR studies microsomal membrane phase behavior, order and dynamics were analyzed. Diabetic samples showed apparent decrease in both frequency and bandwidth. =CH olefinic band integrated area was increased for diabetic samples compared to controls. Alpha-lipoic acid and vitamin C supplemented groups showed similar effects. They tend to restore decreased levels of band frequency and bandwidth. Additive effect between & / #945 / -lipoic acid and vitamin C was seen in some cases that only the combination group achieved to restore control values while & / #945 / -lipoic acid and vitamin C were failed to restore alone.
In conclusion, STZ-induced diabetes mainly caused an increase in antioxidant enzyme activities. Also, increase in lipid peroxidation caused a decrease in the fluidity and order of the membrane resulting in more rigid membrane structures. The loss of cooperation between the antioxidant network may play a role in the secondary complications of diabetes.
| Identifer | oai:union.ndltd.org:METU/oai:etd.lib.metu.edu.tr:http://etd.lib.metu.edu.tr/upload/2/12604947/index.pdf |
| Date | 01 April 2004 |
| Creators | Gorgulu, Guvenc |
| Contributors | Guray, Tulin |
| Publisher | METU |
| Source Sets | Middle East Technical Univ. |
| Language | English |
| Detected Language | English |
| Type | Ph.D. Thesis |
| Format | text/pdf |
| Rights | To liberate the content for public access |
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