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 x kg(-1)) and desferrioxamine (DFO; 50 mg x kg(-1)) on some vascular and biochemical changes associated with streptozotocin (STZ; 65 mg x kg(-1); i.p.)-induced hyperglycaemia were investigated in rats. Both AG and DFO were administered i.p., once daily, for 14 consecutive days to normal and hyperglycaemic animals. The responsiveness of the isolated aortic rings to phenylephrine (PE) was tested. In addition, biochemical markers for oxidative stress such as plasma levels of lipid peroxides and total thiols, as well as the activities of erythrocytic superoxide dismutase (SOD) and whole blood glutathione peroxidase (GSH-Px) were assessed. Results of the present study indicated that induction of hyperglycaemia was associated with increased aortic ring responsiveness to PE, loss in body weight, increase in urine volume, elevation of plasma total thiols and lipid peroxide levels and elevated SOD and GSH-Px enzymatic activities. Treatment of normal rats with AG reduced the response of their aortae to PE. Furthermore, a profound increase in body weight without any significant change in the measured biochemical parameters was observed. In hyperglycaemic animals, AG tended to normalize the enhanced aortic response to PE and modulated STZ-induced biochemical changes without affecting the elevated plasma glucose level. Treatment of normal rats with DFO reduced the response of their aortae to PE and decreased their body weight without altering any of the chosen biochemical parameters. In hyperglycaemic animals, DFO attenuated the responsiveness of their aortae to PE and at the same time, did not affect the loss in body weight and the elevation of plasma glucose level observed in the hyperglycaemic group. Additionally, DFO normalized the elevated plasma level of total thiols and exerted a modulatory influence on the enhanced 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 oxidative stress in the vascular and biochemical changes associated with STZ-induced hyperglycaemia. It is also apparent that advanced glycosylation end products and nitric oxide might be involved. Until clinical studies prove the efficacy and safety of these drugs, specific agents which could scavenge free radicals and block protein glycosylation seem beneficial as a helpful adjunct to the therapy of diabetes.
El-Khatib
A S
AS
Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh 11451, P.O. Box 2457, Kingdom of Saudi Arabia. akhatib@ksu.edu.sa
Moustafa
A M
AM
Abdel-Aziz
A A
AA
Al-Shabanah
O A
OA
El-Kashef
H A
HA
D000704:Analysis of Variance; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002614:Chelating Agents / Q000494:pharmacology; D003676:Deferoxamine / Q000494:pharmacology*; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology*; D006943:Hyperglycemia / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin; D014554:Urination / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D001786:Blood Glucose; D002614:Chelating Agents; D004791:Enzyme Inhibitors; D006146:Guanidines; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D013311:Streptozocin; D003676:Deferoxamine; C004479:pimagedine