Oxidative stress and kidney dysfunction due to ischemia/reperfusion in rat: attenuation by dehydroepiandrosterone.

Publisher: Elsevier Country of Publication: United States NLM ID: 0323470 Publication Model: Print Cited Medium: Print ISSN: 0085-2538 (Print) Linking ISSN: 00852538 NLM ISO Abbreviation: Kidney Int Subsets: MEDLINE

Publication: 2016- : New York : Elsevier
Original Publication: New York, Springer-Verlag.

Oxidative Stress* ; Renal Circulation*; Antioxidants/*pharmacology ; Dehydroepiandrosterone/*pharmacology ; Kidney/*physiopathology ; Reperfusion Injury/*physiopathology; Animals ; Immunohistochemistry ; Kidney/drug effects ; Kidney/pathology ; Male ; Rats ; Rats, Wistar ; Reperfusion Injury/pathology

Background: The pathogenesis of ischemia/reperfusion (I/R) involves generation of reactive oxygen and nitrogen species. This in vivo study investigates the effect of dehydroepiandrosterone (DHEA), a physiologic steroid with antioxidant properties, on oxidative balance and renal dysfunctions induced by monolateral I/R.
Methods: Normal and DHEA-treated rats (4 mg/day x 21 days, orally) were subjected to monolateral renal I/R (30 minutes/6 hours). The oxidative state was determined by measuring hydrogen peroxide level and activities of glutathione-peroxidase, catalase, and superoxide dismutase. Tumor necrosis factor-alpha (TNF-alpha) and nitric oxide production and inducible nitric oxide synthase (iNOS) levels were also measured. Hydroxynonenal content was used to probe lipid peroxidation. Functional parameters determined were creatinine levels and Na/K-ATPase activity. Immunohistochemical and morphologic studies were also performed.
Results: A markedly pro-oxidant state was evident in the kidney of rats subjected to I/R. Both hydrogen peroxide and reactive nitrogen species (nitric oxide and iNOS) increased, whereas antioxidants decreased. Oxidant species induce TNF-alpha increase, which, in turn, produces lipoperoxidative processes, as documented by the increased hydroxynonenal (HNE) level. As final result, impaired renal functionality, hydropic degeneration, and vacuolization of proximal convolute tubules were observed in kidneys of I/R rats. DHEA pretreatment improved the parameters considered.
Conclusion: I/R induces oxidative stress and consequently damages the proximal convolute renal tubules. Rats supplemented with DHEA and subjected to I/R had reduced pro-oxidant state, oxidative damage, and improved renal functionality, indicating an attenuation of oxidative injury and dysfunctions mediated by I/R.

0 (Antioxidants)
459AG36T1B (Dehydroepiandrosterone)

Date Created: 20030813 Date Completed: 20040414 Latest Revision: 20131121

20240513

10.1046/j.1523-1755.2003.00152.x

12911533