The effect of Nrf2-Keap1pathway on the oxidative stress and inflammations in acute kidney injury patients

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.