Activation of nuclear factor erythroid 2‐related factor 2 (Nrf2) and Nrf‐2‐dependent genes by ischaemic pre‐conditioning and post‐conditioning: new adaptive endogenous protective responses against renal ischaemia/reperfusion injury

Abstract

The renoprotective action of Ipre might include early activation and enhanced expression of Nrf2 gene and its dependent antioxidant genes, HO-1 and NOQ1, as endogenous adaptive renoprotective genes, as well as reduction in TNF-α, IL-1β, ICAM-1 and caspase-3.

Possible Underlying Mechanisms of the Renoprotective Effect of Remote Limb Ischemic Preconditioning Against Renal Ischemia/Reperfusion Injury: A Role of Osteopontin, Transforming Growth Factor-Beta and Survivin

“…In consistency with this concept, the present study demonstrated significant increase in MDA and significant reduction in GSH and superoxide dismutase (SOD) activity in the kidney homogenates of rats exposed to I/R injury. These findings are in accordance to various previous studies that reported decreased endogenous enzymatic and non-enzymatic antioxidant systems in the renal tissue after I/R injury [2,13,34]. The renoprotective effect for rIPC might be due to intensification of the antioxidants system and reduction of lipid peroxidation [35].…”

“…Attraction of neutrophils to the post-ischemic tissue is regulated by increase in expression of adhesion molecules such as intracellular cell adhesive molecule (ICAM-1), complement components such as C5a and a number of chemokines such as IL-8 and macrophage inflammatoryprotein-2 (MIP-2) [33]. We reported in previous studies about the upregulation of ICAM-1 in kidney tissues during renal I/R [13]. Enhanced expression of C5a, IL-8, MIP-2 and ICAM-1 facilitate the recruitment and infiltration of circulating leukocytes to the site of injury.…”

“…Also, apoptosis play an important role in development of kidney damage induced by renal ischemia. Also, previous studies reported enhanced expression of apoptotic caspase-3 and anti-apoptotic survivin proteins [12,13] in kidney tissues during renal ischemia. Lastly, osteopontin (OPN), a highly acidic phosphoprotein, is involved in cell adhesion and migration [14,15] and acts as a macrophage and monocyte chemotactic factor by binding to ligands including ᾳvβ3 integrin, CD44, collagen type I and fibronectin [16,17].…”

“…Recent studies by our group showed protective effect for local ischemic preconditioning against renal I/R [13,21]. Furthermore, it has been shown that this protective effect was obtained even when the brief episodes of ischemia were applied to a remote organ, commonly a limb before the definite organ ischemia, a term called remote limb ischemic preconditioning (rIPC) [22].…”

Acute kidney injury

“…The tissue damage is exacerbated by the initiated inflammatory response after reperfusion and re-oxygenation of the kidney. The complex serial events during IRI include the release of reactive oxygen species (ROS) and pro-inflammatory cytokines and chemokines and lead to the activation of apoptotic pathways, intracellular Ca 2+ accumulation and tubular cell injury (Shokeir et al 2014, Malek & Nematbakhsh 2015. The detoxification of ROS during oxidative stress is essential for recovery of the kidney and is, for instance, regulated by the transcription nuclear factor erythroid 2-related factor (Nrf2) that accumulates in the nucleus and activates the transcription of phase 2 enzyme genes, such as haeme-oxygenase-1, glutathione reductase and glutathione peroxidase.…”