Effects of the superoxide dismutase-mimetic compound tempol on endothelial dysfunction in streptozotocin-induced diabetic rats

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

83 Scopus citations

Abstract

Evidence exists to support the beneficial effects of superoxide dismutase on endothelial dysfunction induced by hyperglycemia in vitro. In vivo, however, studies of the effects of native superoxide dismutase preparations on the vascular complications accompanying diabetes are limited, and their therapeutic application potential has so far been disappointing. The objective of this study was to evaluate, for the first time in vivo, the effects of long-term administration of tempol, a stable superoxide dismutase-mimic compound, on diabetes-induced endothelial dysfunction in rats. Diabetes was induced by streptozotocin and rats were monitored for 8 weeks with or without treatment with tempol (100 mg/kg, s.c., b.i.d). Diabetic rats showed increased vascular levels of superoxide, which was accompanied by increased levels of the oxidative stress markers malondialdehyde and 8-epi-prostaglandin F. In addition, the vasorelaxant as well as the cGMP-producing effects of acetylcholine and glyceryl trinitrate were reduced in diabetic rats. Treatment with tempol abolished not only the differences in the vascular content of superoxide, malondialdehyde and 8-epi-prostaglandin F, but also the differences in the relaxation and cGMP responses of aortic rings to both acetylcholine and glyceryl trinitrate between control and diabetic rats. These results support the involvement of reactive oxygen species in mediation of hyperglycemia-induced endothelial dysfunction in vivo, and provide the rationale for potential utilization of stable superoxide dismutase-mimic nitroxides for the prevention of the vascular complications accompanying diabetes.

Original languageAmerican English
Pages (from-to)111-118
Number of pages8
JournalEuropean Journal of Pharmacology
Volume436
Issue number1-2
DOIs
StatePublished - 1 Feb 2002
Externally publishedYes

Bibliographical note

Funding Information:
This study was supported by the Israel Science Foundation of the Israel Academy of Sciences and Humanities and, in part, by a grant from the Yedidut Foundation of Mexico.

Keywords

  • Diabetes
  • Endothelial dysfunction
  • Nitric oxide (NO)
  • Superoxide
  • Superoxide dismutase
  • Tempol

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