Effects of aminoguanidine and desferrioxamine on some vascular and biochemical changes associated with streptozotocin-induced hyperglycaemia in rats

The effects of aminoguanidine (AG; 100 mg kg(-1)) and desferrioxamine (DFO; 50 mg kg(-1)) on some vascular and biochemical changes associated with str eptozotocin (STZ: 65 mg kg(-1); i.p.)-induced hyperglycaemia were investiga ted in rats. Both AG and DFO were administered i.p., once daily, for 14 con secutive days to normal and hvperglycaemic animals. The responsiveness of t he isolated aortic rings to phenylephrine (PE) was tested. In addition, bio chemical markers for oxidative stress such as plasma levels of lipid peroxi des and total thiols, as well as the activities of erythrocytic superoxide dismutase (SOD) and whole blood glutathione peroxidase (GSH-Px) were assess ed. Results of the present study indicated that induction of hyperglycaemia was associated with increased aortic ring responsiveness to PE, loss in bo dy weight. increase in urine volume, elevation of plasma total thiols and l ipid peroxide levels and elevated SOD and GSH-Px enzymatic activities. Trea tment of normal rats with AG reduced the response of their aortae to PE. Fu rthermore, a profound increase in body weight without any significant chang e in the measured biochemical parameters was observed. In hyperglycaemic an imals, AG tended to normalize the enhanced aortic response to PE and modula ted STZ-induced biochemical changes without affecting the elevated plasma g lucose level. Treatment of normal rats with DFO reduced the response of the ir aortae to PE and decreased their body weight without altering any of the chosen biochemical parameters. In hyperglycaemic animals, DFO attenuated t he responsiveness of their aortae to PE and at the same time, did not affec t the loss in body weight and the elevation of plasma glucose level observe d in the hyperglycaemic group. Additionally, DFO normalized the elevated pl asma level of total thiols and exerted a modulatory influence on the enhanc ed activities of SOD and GSH-Px as well as on the increased levels of lipid peroxides. Our data lend further credence for the contribution of oxidativ e stress in the vascular and biochemical changes associated with STZ-induce d hyperglycaemia. It is also apparent that advanced glycosylation end produ cts and nitric oxide might be involved. Until clinical studies prove the ef ficacy and safety of these drugs, specific agents which could scavenge free radicals and block protein glycosylation seem beneficial as a helpful adju nct to the therapy of diabetes. (C) 2001 Academic Press.