Aromatic hydroxylation in animal models of diabetes mellitus

FASEB J. 1998 Nov;12(14):1581-7. doi: 10.1096/fasebj.12.14.1581.


Although the involvement of oxidative stress is well documented in the diabetic state, the individual active oxygen species generated have not been demonstrated in animal models of diabetes currently used. Since streptozotocin-induced diabetes mellitus in animals still serves as an animal model of diabetes mellitus, but streptozotocin induces diabetes and generates oxidative stress per se, we decided to study whether aromatic hydroxylation reflecting hydroxyl radical attack was found in three animal models of diabetes mellitus without streptozotocin induction 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 BB rat to these parameters in the streptozotocin-treated rat. Kidney malondialdehyde concentrations, reflecting lipid peroxidation, pentosidine, and Nepsilon-caboxymethyllysine concentrations, reflecting glycoxidation, were significantly elevated in all diabetic groups as compared to their nondiabetic mates. Aromatic hydroxylation was significantly elevated in the streptozotocin-induced diabetic state exclusively. We conclude that biochemical, pathophysiological, and treatment studies in the streptozotocin model of diabetes mellitus may be confounded by the presence of products, reactions, and tissue damage generated by aromatic hydroxylation reflecting hydroxyl radical attack. We suggest it is not the diabetic state but streptozotocin that generates the hydroxyl radical, as reflected by aromatic hydroxylation in this model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arginine / analogs & derivatives
  • Arginine / metabolism
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / metabolism*
  • Disease Models, Animal
  • Female
  • Fructosamine / blood
  • Hydroxylation
  • Kidney / metabolism
  • Lysine / analogs & derivatives
  • Lysine / metabolism
  • Malondialdehyde / metabolism
  • Mice
  • Rats
  • Rats, Inbred BB
  • Rats, Sprague-Dawley
  • Streptozocin
  • Tyrosine / metabolism


  • Blood Glucose
  • Tyrosine
  • Fructosamine
  • Malondialdehyde
  • Streptozocin
  • N(6)-carboxymethyllysine
  • Arginine
  • pentosidine
  • Lysine