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Abstract
* Diabetes mellitus is a chronic syndrome affecting carbohydrate, fat, protein and nucleic acid metabolism.
* Diabetes also seems to be accompanied by a shortage of antioxidants and an increase in free radicals, the end result being oxidative stress.
* The present study was carried out to determine the role of diabetes in inducing early changes (2 weeks post diabetes induction) on the metabolic pathways of carbohydrates, lipids, proteins and nucleic acids. Oxidative stress markers were also assessed.
* In addition, this study was undertaken to assess the antidiabetic effects of antioxidants mixture, consisting of vitamin E (40 mg/kg wt /day, i.p.) and alpha lipoic acid (10 mg/kg wt /day, i.p.) on experimental diabetic rats.
* Two weeks post treatment, administration of alloxan (125 mg/kg wt, i.p.) to rats resulted in:-
Plasma hyperglycemia and hyperinsulinemia.
Plasma hypercholesterolemia, hypertriglyceridemia, hyperlipidemia.
Increase in the hepatic levels of triglycerides and total lipids.
Increase in the plasma levels of urea, blood urea nitrogen (BUN) and Creatinine.
Increase in the plasma level of uric acid.
Decrease in plasma level of total proteins.
A significant increase in pancreatic thiobarbituric acid reactive substances (TBARS) that was associated with an unaltered level of glutathione (GSH) content of the same organ.
The liver and retina contents of GSH were significantly increased.
The liver and retinal contents TBARS were significantly decreased.
A remarkable decrease in hepatic catalase (CAT) activity.
The inflammatory cytokine tumor necrosis factor-α (TNFα) showed an obvious decrease in its plasma level.
Unchanged levels of plasma and hepatic calcium ions (Ca+2) as well as plasma nitric oxide (NO).
* The obvious feature of the antioxidant treatment against diabetic changes was revealed in:-
The reduction of the plasma level of glucose and increase in insulin level.
A reduction in plasma levels of cholesterol, triglycerides, total lipids as well as the hepatic levels of triglycerides and total lipids.
Decrease in plasma urea, BUN and Creatinine.
Decrease in plasma uric acid levels.
A significant increase in plasma total protein level.
A significant decrease in pancreatic TBARS that was associated with increased level of GSH content of the same organ.
The liver and retinal contents of GSH were significantly decreased.
The liver and retinal contents TBARS were unaltered.
A remarkable increase in hepatic CAT activity.
An obvious decrease in the plasma level of TNFα.
Unchanged levels of plasma and hepatic Ca+2 as well as plasma NO were observed.
* In conclusion, it is obvious from the present study results that early stage (two weeks) of diabetes induced deteriorative changes in carbohydrate, lipid, protein and nucleic acid metabolism. These were accompanied with altered levels of oxidative stress markers in pancreas, liver and retina. These changes point to a more oxidative stress-induced deterioration in the pancreas as compared to liver and retina.
* Moreover, the current data indicated the effective role of vitamin E and alpha lipoic acid combination in combating oxidative stress. This was reflected in the improvement of the metabolism of carbohydrates, lipids, proteins and nucleic acids in antioxidant- treated rats.