Effects of the SOD mimic nitroxide 3-carbamoyl-PROXYL on oxidative stress markers and endothelial dysfunction in streptozotocin-induced diabetic rats.
OBJECTIVE
To evaluate the effects of 3-carbamoyl-PROXYL (CP), a stable superoxide dismutase (SOD) mimic compound, on oxidative stress markers and endothelial dysfunction in diabetic rats.


METHODS
Rats were made diabetic by a single vein injection of streptozotocin (65 mg/kg) and diabetes was verified by the existence of excessive hyperglycemia a week after the treatment. Control and diabetic rats received vehicle or drug for eight weeks, after which the vascular tissue was examined for relaxation and oxidative stress markers.


RESULTS
Diabetic rats showed increased vascular levels of superoxide that were accompanied by increased tissue levels of the oxidative stress markers malondialdehyde (MDA) and 8-iso-prostaglandin F2alpha (8-ISO). The vasorelaxant as well as the cyclic guanosine 5'-monophosphate (cGMP)-producing effects of acetylcholine (ACh) and nitroglycerine were reduced in diabetic rats. Treatment of diabetic rats with CP (50 mg/kg intraperitoneally, bid) abolished not only the differences in superoxide, MDA and 8-ISO levels, but also the differences in the relaxation and cGMP responses of vascular tissue between control and diabetic rats to both ACh and nitroglycerine.


CONCLUSIONS
These results support the involvement of reactive oxygen species in mediation of diabetes-induced endothelial dysfunction in vivo, and provide the rationale for the potential use of SOD mimics in the treatment of diabetes.
Haj-Yehia
Abdullah
A
Department of Pharmaceutics and the David R Bloom Center for Pharmacy;
Nassar
Taher
T
Kadery
Bashir
B
Lotan
Chaim
C
Da'as
Nael
N
Kleinman
Yosef
Y