Lipoperoxidation-derived aldehydes, for example malondialdehyde (MDA), can damage proteins by generating covalent adducts whose accumulation probably participates in tissue damage during aging. However, the mechanisms of adduct formation and their stability are scarcely known. This article investigates whether oxidative steps are involved in the process. As a model of the process, the interaction between MDA and bovine serum albumin (BSA) was analyzed. Incubation of BSA with MDA resulted in rapid quenching of tryptophan fluorescence and appearance of MDA protein adduct fluorescence; transition metal ion traces interfered with the latter process. MDA induced generation of peroxides in BSA, which was preventable with the antioxidant 2,6,-di-tert-butyl-4-methylphenol (BHT). MDA-exposed BSA underwent aggregation, degradation, and BHT-sensitive "gel retardation" effects. Phycoerythrin fluorescence disappearance, a marker of damage mediated by reactive oxygen species, indicated synergism between MDA and metal ions. The interaction between reactive aldehydes and proteins is likely to occur in several steps, some of them oxidative in nature, giving rise to advanced lipoperoxidation end-products, which could participate, with advanced glycation end-products, in the generation of tissue damage during aging.

This study analyzes the effect of chronic treatment with different antioxidants (N-acetyl-cysteine [NAC], taurine, a combination of NAC and taurine, and oxerutin) on long-term experimental diabetes induced by streptozotocin in rats. Glycoxidative damage was evaluated in the skin; glomerular structural changes were studied with morphometry and immunohistochemistry. Oxerutin treatment and the combined NAC plus taurine treatment resulted in reduced accumulation of collagenlinked fluorescence in skin in comparison with untreated diabetic rats. All treatments except taurine reduced glomerular accumulation of N ⑀ -(carboxymethyl)lysine and protected against the increase in glomerular volume typical of diabetes; furthermore, the apoptosis rate was significantly decreased and the glomerular cell density was better preserved. Glycoxidative markers in the skin turned out to be good indicators of the glomerular condition. The findings that emerged from our study support the hypothesis that glomerular damage in diabetes can be prevented or at least attenuated by supplementation with specific antioxidants. Treatment with oxerutin and combined treatment with NAC plus taurine gave the most encouraging results, whereas the results of taurine-only treatment were either negligible or negative and therefore suggest caution in the use of this molecule in single-drug treatment courses. Diabetes 52: 499 -505, 2003

Heme oxygenase 1 (HO-1) expression is recognized as a marker of cellular response to oxidative stress; since ageing is believed to be related to oxidative "wear and tear", HO-1 may represent a candidate biomarker of ageing. In our study, the hepatic expression of HO-1 mRNA, evaluated by RT-PCR in 2.5-24 month-old rats, was higher at 6 months than at 2.5 months of age, but thereafter increased no further: on the contrary, a declining trend was observed. However, while 2.5 month-old rats responded to acute ethanol intoxication by displaying increased expression of liver HO-1 mRNA, and 6 month-old rats exhibited a mild response, 18 month-old rats did not show any response; this phenomenon suggests that during development and ageing the transcriptional response to oxidative stress decreases. In our view, the finding that HO-1 expression did not increase progressively during ageing may be explained by a decreased transcriptional ability to respond to stress in older animals, rather than by a reduction in oxidative stress.