Intermedin protects against renal ischemia-reperfusion injury by inhibition of oxidative stress

Abstract

Reactive oxygen species (ROS) play a critical role in renal ischemia-reperfusion injury (IRI). Intermedin (IMD) reportedly protected against myocardial IRI via its antioxidant effects; however, its protective role in renal IRI has not been investigated. We overexpressed IMD in rat kidneys and examined how the kidneys respond to renal IRI. Eukaryotic expression plasmid encoding the rat IMD gene or control empty vector was transfected into the left kidney using an ultrasound-microbubble-mediated delivery system. This method yielded high expression of IMD in kidney cells. Renal IRI was induced by clamping the left renal artery followed by reperfusion. In response to IRI, overexpression of IMD in the kidney significantly improved renal function and pathology compared with the kidney transfected with control plasmid. We investigated the mechanisms by which IMD protects against renal IRI. We examined renal superoxide dismutase (SOD) activity and malondialdehyde (MDA) content and found SOD activity was significantly increased, while MDA level was markedly decreased in kidneys transfected with IMD, suggesting ROS production and oxidative stress were reduced by IMD overexpression. We also measured myeloperoxidase (MPO) activity, tubular cell apoptosis, and the expression of intercellular adhesion molecule-1 (ICAM-1), P-selectin, and endothelin-1 (ET-1) in the kidney. Renal MPO activity and the expression of ICAM-1, P-selectin, and ET-1 stimulated by IRI were significantly inhibited by IMD overexpression. Moreover, IMD overexpression prevented kidney cells from apoptosis caused by IRI. Our results demonstrate that overexpression of IMD in the kidney protects against renal IRI, apparently by reducing oxidative stress, consequently suppressing inflammation and vasoconstrictor production and apoptosis.

Effects of Flaxseed oil supplementation on renal dysfunction due to ischemia/reperfusion in rat

“…In the current study, ischemia reperfusion resulted in increased MDA level as a lipid peroxidation production and decreased SOD level. These findings confirm the renal tissue changes in the pathological points and the impaired renal function as described before .A major cellular defense against ROSs is provided by SOD and catalase, which together converts superoxide radicals first to H2O2 and then molecular oxygen and water (24). Although, the mechanism of renal IR injury has been understood for several decades, no effective therapies are introduced yet (25).…”

Propofol Prevents Renal Ischemia-Reperfusion Injury via Inhibiting the Oxidative Stress Pathways

“…Zou et al found that pioglitazone protected against renal ischemia-reperfusion injury by increasing the level of enzymatic activities of superoxide dismutase and enhancing antioxidant capacity [43]. Similar mechanisms were seen in the protective effects of curcumin and intermedin [44] It was reported that propofol had anti-oxidative activity [45]. Propofol scavenges H 2 O 2 and reduces the formation of lipid peroxides [46], which validates in heart protection [47,48].…”

The protective effect of nesfatin-1 against renal ischemia–reperfusion injury in rats

“…3 A substantial amount of study to date has focused on the mechanism of oxidative stress and cell apoptosis in renal I/R injury, so many therapeutic method aimed at oxidative stress and apoptosis has been reported to protection renal injury. [26][27][28] Nesfatin-1, an 82-amino-acid peptide, has been reported to possess antioxidative, antiinflammation and anti-apoptotic properties. Previous study showed the neuroprotection of nesfatin-1 against SAHinduced injury in rats by inhibiting inflammation and apoptosis.…”