Effect of milrinone on the inflammatory response and NF-kB activation in renal ischemia-reperfusion injury in mice

Abstract

BackgroundMilrinone increases intracellular adenosine 3',5'-cyclic monophosphate concentration and enhances vascular relaxation. Nuclear factor-kappa B (NF-kB) plays a key role in inflammatory responses during ischemia-reperfusion (I/R) injury. We aimed to investigate the effect of milrinone on the inflammatory responses and NF-kB activation in renal I/R injury in mice.MethodsThirty C57BL/6 mice were allocated into 3 groups. In group S (n = 10), only right nephrectomy was done. In group C (n = 10), the left kidney was subjected to 30 min of ischemia after right nephrectomy. In group M (n = 10), milrinone (5 µg/kg) was administered before ischemia. After 24 hours of reperfusion, the serum creatinine was measured, kidney samples were obtained for histology, and expressions of NF-kB and proinflammatory cytokines were analyzed.ResultsIn group C, the serum creatinine concentration was markedly elevated, compared with group S. Creatinine concentration in group M was also elevated, but it was significantly lower than that in group C. Histologic evidence of renal damage was severe in group C, but it was improved in group M. In groups C and M, expression of NF-kB, tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-2 (MIP-2) mRNA increased significantly compared with group S (P < 0.05). But group M showed a lower expression of NF-kB, TNF-α, ICAM-1, MCP-1 and MIP-2 mRNA than group C (P < 0.05).ConclusionsMilrinone treatment attenuates the renal inflammatory response and activation of NF-kB, resulting in improvement of renal function and tissue injury.

Renoprotective approaches and strategies in acute kidney injury

“…In 2004, Cao and colleagues reported that transfection of NF-κB decoy oligodeoxynucleotides abolished NF-κB activation in ischemic AKI, resulting in decreases in MCP-1 and ICAM-1 expression, suppression of monocyte/ macrophage infiltration, and significant attenuation of tissue damage (Cao et al, 2004). Consistently, NF-κB activation was inhibited by pharmacologic agents such as milrinone and resveratrol or overexpression of SIRT1, resulting in a better preservation of renal histology and function in ischemic-AKI and cisplatin nephrotoxic (Jung et al, 2014; Jung et al, 2012). Blockade of NF-κB was also implicated in the protective effect of Nrf2 signaling (Jiang et al, 2014).…”

Berberine attenuates ischemia–reperfusion injury through inhibiting HMGB1 release and NF-κB nuclear translocation

“…Data are presented as the mean ± SD. # P < 0.01 versus the sham group; *P < 0.01 versus the vehicle group enzymes, and cytokines, such as TNF-α, IL-1β, and IL-6, to initiate inflammatory responses [31]. A previous study reported that the inhibition of NF-κB signaling is neuroprotective because it reduces infarct size, improves neurological deficits, and leads to the inhibition of the expression of inflammatory response genes [32], suggesting that targeting NF-κB activity after acute cerebral infarction may be a potential therapeutic strategy.…”

Necroptosis Contributes to Urban Particulate Matter-Induced Airway Epithelial Injury

“…Several studies indicate that NF-κB plays a strong role in the initiation of inflammatory responses [39-41]. Recently, RIPK3, the critical biomarker for necroptosis, was shown to facilitate inflammation through NF-κB [26, 42].…”