The Role of Some Antioxidants in Diabetes Mellitus Induced in Rats

The aim of the present study was to examine the involvement of oxidative stress in the
progression of pancreatic β-cell dysfunction in type 1 diabetes and to evaluate the
potential usefulness of some antioxidants supplementation in the treatment of type 1
diabetes. The severity of diabetes in the different groups has been studied in relation
to the level of cytokines released during the oxidative stress. The present study was
achieved using 24 male Sprague Dawley albino rats. Rats were divided into three
groups: normal control rats, diabetic control rats, and diabetic rats received mixture
of antioxidants. A mixture of antioxidants [N-acetyl-cysteine (NAC), alpha-lipoic acid
(LA), vitamin E and vitamin C] was orally administered daily to cyclophosphamideinduced
diabetic rats for a period of two months. The results revealed that diabetic
rats had significant increase in tumor necrosis factor-α (TNF-α) concentration and
transcription nuclear factor-kappa beta (NF-кβ) concentration, as compared to
normal control rats. After treatment of diabetic rats with the antioxidants for two
months, tumor necrosis factor-α (TNF-α) and nuclear factor-kappa beta (NF-кβ)
concentrations showed a highly significant decrease (p< 0.001) when compared with
the diabetic control group. Histological analysis of the pancreas revealed that the
antioxidants treatment preserved the normal morphology of Islets of pancreas, and β-
cell mass when compared with diabetic rats. The combination of these antioxidants
was more effective in suppression of apoptosis which was associated with the
development of type 1 diabetes. Immunohistochemical analysis indicated that
antioxidants protect β-cell from cytokine induced dysfunction and death through
inhibition of specific nuclear factor –кβ activity which was more visible in the nuclei
of Islet cells in diabetic rats than antioxidants-treated rats. On the basis of the present
results it could be concluded that [N-acetyl-cysteine (NAC), alpha-lipoic acid (LA),
vitamin E and vitamin C] restored the activities of the above parameters in different
ways, depending on special mechanism in each one. Supplementation of antioxidants
at once after diagnosis of diabetes may delay the complications of diabetes. This
finding suggests a potential usefulness of antioxidants for treating diabetes and
provides further support for the implication of oxidative stress in β-cell dysfunction in
diabetes by providing protection against hyperglycemia.