IMMUNOLOGICAL EVIDENCE FOR INCREASED OXIDATIVE STRESS IN DIABETIC RATS

The role of oxidative stress in aging and diabetes mellitus is current ly under discussion. We previously showed age-dependent accumulations of fluorescent protein adducts with lipoperoxidative aldehydes, (malon dialdehyde (MDA), and hydroxynonenal (HNE)) in rat skin collagen with diabetic BB rats exhibiting faster accumulation. Modified proteins hav e been shown to be immunogenic: antibody titres against rat serum albu min modified by MDA and HNE (MDA-RSA and HNE-RSA) or oxidized by react ive oxygen species were measured by ELISA as markers of oxidative dama ge in BE diabetic and non-diabetic rats, Each tested antibody titre wa s significantly higher in the diabetic than in the non-diabetic rats. A significant correlation existed between anti-MDA-RSA and anti-HNE-RS A antibody titers. Only the anti-HNE-RSA antibody titre increased sign ificantly with age (p = 0.052) in diabetic animals, while no titres in creased significantly in non-diabetic animals. A major factor which co rrelated with the development of these antibodies was diabetes duratio n: this was significant (p = 0.032) for anti-HNE-RSA antibody titre an d slightly significant (p = 0.05) for anti-MDA-RSA antibody titre. Thu s, chronic hyperglycaemia is probably fundamental in the increase of o xidative stress. There is correlation between anti-aldehyde-RSA antibo dy titres and the corresponding aldehyde-related collagen-linked fluor escence: modified collagen may play a part in the observed immune resp onse. Our data indicate a stronger immune response of diabetic rats ag ainst proteins modified by lipoperoxidative aldehydes and oxygen free radicals, and they support the hypothesis of increased oxidative damag e in diabetes.