title: Nitro-oleic acid protects the mouse kidney from ischemia and reperfusion injury.
abstract: Nitroalkene derivatives of linoleic acid (nitrolinoleic acid; LNO2) and nitro-oleic acid (OA-NO2) are endogenous lipid products with potent anti-inflammatory properties. The present study was undertaken to evaluate the therapeutic potential of OA-NO2 in a mouse model of renal ischemia-reperfusion (I/R) injury. B6129SF2/J mice were subjected to bilateral renal ischemia for 30 min, followed by 24 h of reperfusion. Fifty minutes after ischemia, mice received intraperitoneal (ip) injections of OA-NO2 (500 microg/kg; I/R OA-NO2), vehicle for OA-NO2 (i.e., 0.8 ml/kg ethanol; I/R veh), or oleic acid (500 microg/kg; I/R OA) every 6 h during the 24-h recovery period. A sham-operated group was not subjected to ischemia and received 0.8 ml/kg ethanol ip every 6 h during the 24-h recovery period (sham veh). While plasma urea and creatinine were elevated (P<0.05) in I/R veh vs. sham veh mice, the severity was less (P<0.05) in I/R OA-NO2 animals. Indices of histological damage, polymorphonucleocyte infiltration, together with expression of intracellular adhesion molecule-1, interleukin-1beta, and tumor necrosis factor-alpha, p47(phox), and gp91(phox) were greater in I/R veh vs. sham veh mice, but were attenuated (P<0.05) in I/R OA-NO2 animals. Because indices of renal dysfunction were similar between I/R veh and I/R OA mice (P>0.05), but less (P<0.05) in I/R OA-NO2 animals compared with both groups, protection from bilateral renal ischemia is afforded by the nitrated but not free form of oleic acid. Together, delayed administration of nitrated fatty acid OA-NO2 attenuates renal I/R injury in the mouse likely via inhibition of the inflammatory response.
authors.affiliation: Department of Internal Medicine, University of Utah and Salt Lake Veteran Affairs Medical Center, 30 N 1900 E, Rm. 4R312, Salt Lake City, UT 84132, USA.
authors.forename: Haiying
authors.initials: H
authors.lastname: Liu
authors.forename: Zhanjun
authors.initials: Z
authors.lastname: Jia
authors.forename: Zhunjun
authors.initials: Z
authors.lastname: Jia
authors.forename: Sunhapas
authors.initials: S
authors.lastname: Soodvilai
authors.forename: Guangju
authors.initials: G
authors.lastname: Guan
authors.forename: Mong-Heng
authors.initials: MH
authors.lastname: Wang
authors.forename: Zheng
authors.initials: Z
authors.lastname: Dong
authors.forename: J David
authors.initials: JD
authors.lastname: Symons
authors.forename: Tianxin
authors.initials: T
authors.lastname: Yang