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Favorable balance of anti-oxidant/pro-oxidant systems and ablated oxidative stress in Brown Norway rats in renal ischemia-reperfusion injury. Mol Cell Biochem 2007 Oct;304(1-2):1-11

Date

04/27/2007

Pubmed ID

17458515

DOI

10.1007/s11010-007-9480-z

Scopus ID

2-s2.0-34648835021 (requires institutional sign-in at Scopus site)   29 Citations

Abstract

Oxidative stress is important in the pathogenesis of renal ischemia-reperfusion (IR) injury; however whether imbalances in reactive oxygen production and disposal account for susceptibility to injury is unclear. The purpose of this study was to compare necrosis, apoptosis, and oxidative stress in IR-resistant Brown Norway rats vs. IR-susceptible Sprague-Dawley (SD) rats in an in vivo model of renal IR injury. As superoxide (O (2) (.-) ) interacts with nitric oxide (NO) to form peroxynitrite, inducible NO synthase (iNOS) and nitrotyrosine were also examined. Renal IR was induced in SD and BN rats by bilateral clamping of renal arteries for 45 min followed by reperfusion for 24 h (SD 24 and BN 24, respectively). BN rats were resistant to renal IR injury as evidenced by lower plasma creatinine and decreased acute tubular necrosis. TUNEL staining analysis demonstrated significantly decreased apoptosis in the BN rats vs. SD rats after IR. Following IR, O (2) (.-) levels were also significantly lower in renal tissue of BN rats vs. SD rats (P < 0.05) in conjunction with a preservation of the O (2) (.-) dismutating protein, CuZn superoxide dismutase (CuZn SOD) (P < 0.05). This was accompanied by an overall decrease in 4-hydroxynonenal adducts in the BN but not SD rats after IR. BN rats also displayed lower iNOS expression (P < 0.05) resulting in lower tissue NO levels and decreased nitrotyrosine formation (P < 0.01) following IR. Collectively these results show that the resistance of the BN rat to renal IR injury is associated with a favorable balance of oxidant production vs. oxidant removal.

Author List

Nilakantan V, Hilton G, Maenpaa C, Van Why SK, Pieper GM, Johnson CP, Shames BD

Authors

Christopher P. Johnson MD Professor in the Surgery department at Medical College of Wisconsin
Scott K. Van Why MD Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Acute Kidney Injury
Animals
Antioxidants
Apoptosis
Kidney
Lipid Peroxidation
Nitric Oxide
Nitric Oxide Synthase Type II
Oxidative Stress
Rats
Rats, Inbred BN
Rats, Sprague-Dawley
Reactive Oxygen Species
Reperfusion Injury
Superoxide Dismutase
Superoxides