AROMATIC HYDROXYLATION IN ANIMAL-MODELS OF DIABETES-MELLITUS

Although the involvement of oxidative stress is well documented in the diabetic state, the individual active oxygen species generated have m ot been demonstrated in animal models of diabetes currently used. Sinc e streptozotocin-induced diabetes mellitus in animals still serves as an animal model of diabetes mellitus, but streptozotocin induces diabe tes and generates oxidative stress per se, we decided to study whether aromatic hydroxylation reflecting hydroxyl radical attack was found i n three animal models of diabetes mellitus without streptozotocin indu ction or in streptozotocin-induced diabetes only, For this purpose, we compared lipid peroxidation, aromatic hydroxylation of phenylalanine, glycoxidation in genetically determined diabetic mouse strains db/db and kk, and the diabetic BE rat to these parameters in the streptozoto cin-treated rat. Kidney malondialdehyde concentrations, reflecting lip id peroxidation, pentosidine, and N-epsilon-caboxymethyllysine concent rations, reflecting glycoxidation, were significantly elevated in all diabetic groups as compared to their nondiabetic mates, Aromatic hydro xylation was significantly elevated in the streptozotocin-induced diab etic state exclusively. We conclude that biochemical, pathophysiologic al, and treatment studies in the streptozotocin model of diabetes mell itus may be confounded by the presence of products, reactions, and tis sue damage generated by aromatic hydroxylation reflecting hydroxyl rad ical attack. We suggest it is not the diabetic state but streptozotoci n that generates the hydroxyl radical, as reflected by aromatic hydrox ylation in this model.