Remote limb ischemic pre-conditioning prevents renal Ischemia/reperfusion injury in rats by modulating oxidative stress and TNF-α/NF-κB/TGF-/βapelin signaling pathway.

Abstract

Remote limb ischemic pre-conditioning (RIPreC) can invoke potent renal protection. The involvement of oxidative stress and inflammatory pathways in renal ischemia/reperfusion injury (I/RI) was also confirmed. This study was designed to investigate the RIPreC effects on IRI-induced kidney dysfunction in rats through NFĸB/TNF-α/TGF-ꞵ/apelin signaling pathway. Renal I/RI was induced by occluding the kidney arteries for 45min, then reperfusion for 24h. Four similar cycles of left femoral artery ischemia (2min)/reperfusion (3min) before the onset of kidney ischemia were performed to create RIPreC. Animals were randomly divided into three groups: sham, I/R, and RIPreC + I/R. Following the reperfusion phase, urine and blood samples were taken, and the kidney was removed for functional, molecular, and histological examination. When compared to sham rats, renal IRI resulted in decreased creatinine clearance and increased sodium fractional excretion, lower antioxidant enzyme activities, higher malondialdehyde content and higher nuclear factor-kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α), transforming growth factor-betta (TGF-β), and Apelin expression levels, and histologically damaged kidney tissue. All of the alterations, as mentioned earlier, were alleviated using the RIPreC treatment. Thus, RIPreC can protect against renal dysfunction after renal I/RI via modulation of the TNF-α/NF-κB/TGF-ꞵ/Apelin signaling pathway and strengthening the antioxidant defense system.