Amelioration of Renal Ischemia–Reperfusion Injury by Inhibition of IL-6 Production in the Poloxamer 407–Induced Mouse Model of Hyperlipidemia

Abstract

Abstract. It is largely unknown whether hyperlipidemia is involved in the pathobiology of renal ischemia-reperfusion (I/R) injury that is an important cause of acute kidney injury. Here we studied the effect of experimental dyslipidemia on renal I/R injury. Renal I/ R injury was less severe in hyperlipidemic mice treated with poloxamer 407 than in the control mice. Cytokine analyses revealed decreased levels of renal and serum IL-6 in the hyperlipidemic mice after renal I/ R. Protection from renal I /R injury in the hyperlipidemic mice was diminished by administration of recombinant IL-6. Concanavalin A-induced IL-6 release from cultured splenocytes derived from the hyperlipidemic mice was lower than that from splenocytes of normal mice. In hypercholesterolemic apolipoprotein E-knockout mice, in which renal I/R injury is less severe than in control mice, renal I /R-induced IL-6 production was also less than that in controls. In angiopoietin-like 3-deficient mice, which were hypolipidemic, renal dysfunction and renal IL-6 level after I /R were similar to those of control mice. Our data indicate that the presence of experimental hyperlipidemia may be associated with a decreased risk of renal I/R injury, possibly mediated by reduced renal IL-6 production after the insult and extend the notion that an anti-IL6 agent would be useful for the treatment of acute kidney injury.

Development of a novel model of hypertriglyceridemic acute pancreatitis in mice

“…Although P-407 is also a non-ionic surface active agent, like TritonWR 1339, but the physiological toxicity of P-407 is low and the plasma triglyceride level of mice can be maintained stably at 5000 mg/dl after the prolonged stimulation with P-40714. Compared with genetically modified animal models, this novel HTG model has the advantages of simple operation, low cost and plasma lipid matching with HTG-AP patients, consequently imitating the pathophysiological process of such patients well.…”

“…Poloxamer 407 (P-407) is a hydrophilic triblock copolymer comprised of polyoxyethylene and polyoxypropylene units and has been reported to induce HTG with little side effects14. P-407 can increase the serum triglyceride concentrations by directly inhibiting the activity of both LPL and hepatic lipase, which were combined with the capillary wall1516.…”

“…P-407 can increase the serum triglyceride concentrations by directly inhibiting the activity of both LPL and hepatic lipase, which were combined with the capillary wall1516. Physiological toxicity of P-407 is so low that both short-term and long-term use can induce high serum triglyceride levels in mice14. Saja et al 17.…”

Effects of thyroid hormone analogue and a leukotrienes pathway-blocker on renal ischemia/reperfusion injury in mice

“…According to Sharyo et al (2009) [42], after anesthesia, an abdominal incision was made and the renal pedicles were dissected bilaterally. A vascular clamp (Biotechno, Germany) was placed on each renal pedicle for 30 min.…”

Effect of Intervention in Mast Cell Function Before Reperfusion on Renal Ischemia-Reperfusion Injury in Rats

“…It has been reported that the histamine antagonist ketotifen could improve the survival rate of rats subjected to intestinal ischemia reperfusion injury [6]. Other reports demonstrated that inhibition of inflammatory factors such as TNF-α, IL-6, and ICAM-1, as well as inhibition of lipid peroxidation can all protect kidneys against renal ischemia reperfusion-induced injury [7][8][9].…”