The Nrf2/HO-1 Pathway Mediates the Antagonist Effect of L-Arginine On Renal Ischemia/Reperfusion Injury in Rats

Kidney and Blood Pressure Research - Tập 42 Số 3 - Trang 519-529 - 2017
Fei Tong1, Xinmei Zhou1
1a

Tóm tắt

<b><i>Background/Aims:</i></b> Ischemia/reperfusion (I/R) is the most common cause of acute renal injury. I/R-induced oxidative stress is involved in the development of acute renal injury, which can be reversed by supplementation with L-arginine, a precursor of nitric oxide (NO). This study was conducted to evaluate alterations in the expression of transcription factors [nuclear factor kappa B (NF-κB), nuclear factor-E2-related factor-2 (Nrf2), and heme oxygenase 1 (HO-1)] and heat shock protein 70 (HSP70) in the kidney of I/R-induced injury rats. <b><i>Methods:</i></b> Sprague-Dawley (SD) rats were subjected to bilateral renal ischemia for 45 min followed by reperfusion for 24 h. Group 1, Sham; group 2, I/R; group 3, L-arginine; and group 4, L-arginine+zinc protoporphyrin (ZnPP). The levels of serum creatinine (Scr), blood urea nitrogen (BUN), serum nitric oxide (NO), histic malondialdehyde (MDA) and reactive oxygen species (ROS) and superoxide dismutase (SOD) activity were determined, and the expression levels of Nrf2, HO-1, NF-κB, and HSP70 were evaluated. <b><i>Results:</i></b> The treatment of rats with L-arginine produced a significant reduction in the levels of BUN, Scr, MDA and a significant enhancement in the level of NO and in the activity of SOD compared to renal I/R groups. The expression levels of Nrf2, HO-1, and HSP70 were strongly increased, and the expression of NF-κB and production of ROS were significantly decreased in the L-arginine group compared to that of the I/R group. ZnPP increased renal damage and displayed effects opposite to those of L-arginine. <b><i>Conclusion:</i></b> These findings suggested that L-arginine/NO reduces renal dysfunction associated with I/R of the kidney and may act as a trigger to regulate the NF-κB, HSP70 and Nrf2/HO-1 signaling cascades.

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Kidney and Blood Pressure Research

Tập 42 Số 3

519-529

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