Journal
JOURNAL OF PHARMACOLOGICAL SCIENCES
Volume 110, Issue 1, Pages 47-54Publisher
JAPANESE PHARMACOLOGICAL SOC
DOI: 10.1254/jphs.08283FP
Keywords
renal ischemia-reperfusion injury; IL-6; poloxamer 407; angiopoietin-like 3-deficient mouse; apolipoprotein E-knockout mouse
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Funding
- SPS KAKENHI [19580342]
- Grants-in-Aid for Scientific Research [19580342] Funding Source: KAKEN
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It is largely unknown whether hyperlipidemia is involved in the pathobiology of renal ischemia-reperfusion (I/R) injury that is ail 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 all anti-IL6 agent Would be useful for the treatment Of acute kidney injury.
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