Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2002 Fall;7(2-3):85-92.

Effects of the SOD mimic nitroxide 3-carbamoyl-PROXYL on oxidative stress markers and endothelial dysfunction in streptozotocin-induced diabetic rats

Abdullah Haj-Yehia  1 , Taher Nassar, Bashir Kadery, Chaim Lotan, Nael Da'as, Yosef Kleinman
Affiliations

Effects of the SOD mimic nitroxide 3-carbamoyl-PROXYL on oxidative stress markers and endothelial dysfunction in streptozotocin-induced diabetic rats

Abdullah Haj-Yehia et al. Exp Clin Cardiol. 2002 Fall.

Abstract

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.

Animals and 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.

Keywords: Endothelial dysfunction; Isoprostanes; Lipid peroxidation; Nitric oxide; Relaxation; Superoxide; cGMP.

PubMed Disclaimer

Figures

Figure 1)
Figure 1)
Relaxations of rat aortic rings from control, diabetic and 3-carbamoyl-PROXYL (CP)-treated diabetic rats in response to acetylcholine (ACh). *Significantly different from the corresponding values of diabetic rats (n=8, P<0.05)
Figure 2)
Figure 2)
Relaxations of rat aortic rings from control, diabetic and 3-carbamoyl-PROXYL (CP)-treated diabetic rats in response to nitroglycerine (NTG). *Significantly different than the corresponding values of diabetic rats (n=8, P<0.05)
Figure 3)
Figure 3)
Basal cyclic guanosine 5′-monophosphate (cGMP) levels in rat aortic tissue from control, diabetic and 3-carbamoyl-PROXYL (CP)-treated diabetic rats. *Significantly greater than in diabetic rats (n=8, P< 0.05)
Figure 4)
Figure 4)
Cyclic guanosine 5′-monophosphate (cGMP) levels in response to 10–6 M acetylcholine (ACh) of rat aortic tissue from control, diabetic and 3-carbamoyl-PROXYL (CP)-treated diabetic rats. *Significantly greater than in diabetic rats (n=8, P<0.001)
Figure 5)
Figure 5)
Cyclic guanosine 5′-monophosphate (cGMP levels (pmol/g wet weight) in response to 10–6 M nitroglycerine (NTG) of rat aortic tissue from control, diabetic and 3-carbamoyl-PROXYL (CP)-treated diabetic rats. *Significantly greater than in diabetic rats (n=8, P<0.05)
Figure 6)
Figure 6)
Basal superoxide production in thoracic aorta from control, diabetic and 3-carbamoyl-PROXYL (CP)-treated diabetic rats. Data are mean ± SE of four experiments each representing aortas pooled from six rats. *Significantly greater than in control or CP-treated diabetic rats (P<0.001)
Figure 7)
Figure 7)
Aortic 8-iso-prostaglandin F2α (8-ISO) content of control, diabetic and 3-carbamoyl-PROXYL (CP)-treated diabetic rats. Data are mean ± SE of four experiments each representing aortas pooled from six rats. *Significantly greater than in control or CP-treated diabetic rats (P<0.001)
Figure 8)
Figure 8)
Malondialdehyde (MDA) content in aorta from control, diabetic and 3-carbamoyl-PROXYL (CP)-treated diabetic rats. Data are mean ± SE of four experiments each representing aortas pooled from six rats. *Significantly greater than in control or CP-treated diabetic rats (P<0.001)
None
None
None
None
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Giugliano D, Ceriello A, Paolisso G. Diabetes mellitus, hypertension, and cardiovascular disease: Which role for oxidative stress? Metabolism. 1995;44:363–8. - PubMed
    1. Cannon RO., III Role of nitric oxide in cardiovascular disease: focus on the endothelium. Clin Chem. 1988;44:1809–19. - PubMed
    1. Oyama Y, Kawasaki H, Hattori Y, Kanno M. Attenuation of endothelium-dependent relaxation in aorta from diabetic rats. Eur J Pharmacol. 1986;131:75–8. - PubMed
    1. Pieper GM, Gross GJ. Oxygen free radicals abolish endothelium-dependent relaxation in diabetic aorta. Am J Physiol. 1988;255:H825–33. - PubMed
    1. Diederich D, Skopec J, Diederich A, Dai FX. Endothelial dysfunction in mesenteric resistance arteries of diabetic rat: role of free radicals. Am J Physiol. 1994;266:H1153–61. - PubMed

LinkOut - more resources