ISSN 2320-5407 International Journal of Advanced Research (2016), Volume 4, Issue2, 424-433 424 Journal homepage: http://www.journalijar.com INTERNATIONAL JOURNAL OF ADVANCED RESEARCH RESEARCH ARTICLE The effect of Nrf2-Keap1pathway on the oxidative stress and inflammations in acute kidney injury patients * Howaida Attia Nounou 1 , Manal Ali Shalaby 2 , and Iman E El Gohary 3 1. Department of Medical Biochemistry, Faculty of Medicine, Alexandria University, Egypt 2. Department of Medical Biotechnology, Genetic Engineering and Biotechnology Research Institute (GEBRI), City for Scientific Research and Technology Applications, Alexandria, Egypt 3. Department of Internal Medicine- Nephrology unit, Faculty of Medicine, Alexandria University, Egypt Manuscript Info Abstract Manuscript History: Received: 15 December 2015 Final Accepted: 26 January 2016 Published Online: February 2016 Key words: Acute kidney injury, Heme oxygenase-1, High sensitive C- reactive protein, Kelch-like ECH- associated protein 1, Nitric oxide; Reduced glutathione. *Corresponding Author Howaida Attia Nounou. Background: Inflammation and oxidative stress are always considered as key players in the pathophysiology of acute kidney injury (AKI). Nuclear factor erythroid-2-related factor-2 (Nrf2) pathway confers protection against tissue injury by orchestrating antioxidant and detoxification responses to oxidative stress. Aim: This research aimed to investigate the effect of nuclear factor erythroid-2-related factor-2 - Kelch-like ECH-associated protein 1 (Nrf2- Keap1) pathway on the oxidative stress and inflammations in AKI patients. Subjects and Methods: This study examined the plasma levels of reduced glutathione (GSH) and nitric oxide (NO) colorimetrically, and high sensitive- C reactive protein (hsCRP) and Kelch-like ECH-associated protein 1 (Keap- 1) by ELISA method in 30 AKI patients and 30 matched controls. Plasma heme oxygenase-1 (HO-1) was also assessed by western blotting. Results: The hsCRP and keap-1 levels were significantly higher (P <0.001), whereas NO and GSH levels were significantly diminished (P= 0.015, P= 0.007 respectively) in AKI group compared to the control group. The decline in NO and GSH levels were 31.78% and 32.77% respectively, while the rise of Keap-1 was 103.52 % in the AKI group relative to the controls. Western blotting analysis demonstrated overexpression of plasma HO-1 in the AKI patients compared to the controls. Conclusion: Our study concluded that despite Keap-1 was increased in AKI group, various oxidative stresses that prone to accompany AKI may modify its cysteine residues that could avert proteasomal degradation of Nrf2. Upregulation of Nrf2 target gene products including the antioxidant enzyme HO-1 may be one of the compensatory mechanisms that could ameliorate the effect of oxidative stress in AKI. Copy Right, IJAR, 2016,. All rights reserved. Introduction:- Acute kidney injury (AKI) occurs in up to 7% of hospitalized patients (Lameire et al., 2006). Whereas 25% of patients in the intensive care unit (ICU) develop AKI and 5% of patients in the ICU would need renal replacement therapy (Lameire et al., 2006 and Waikar et al., 2007). Despite the extensive use of both intermittent hemodialysis (IHD) and continuous renal replacement therapy (CRRT), the mortality of AKI is considerably as high as 80% in ICU patients (Liano and Pascual, 1996 and Liano et al., 1998). Recently, Wang et al., (2012) concluded that AKI occurred in over 1 of 5 hospitalizations and was associated with a more than fourfold increased likelihood of death. AKI can result from mechanical trauma, ischemia/reperfusion, sepsis, toxins or nephrotoxic medication (Nath and Norby, 2000 and Pannu and Nadim , 2008). A better understanding of the different mechanisms that underlie AKI, and the biological aspects that determine the balance between renal adaptation and dysfunction, is vital to reduce clinical burden and patient suffering (Shelton et al., 2013).