Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
6251392 | International Journal of Surgery | 2015 | 5 Pages |
â¢Limb ischemia reperfusion is common and increases patient morbidity and mortality.â¢ROS produced by ischemia reperfusion play a significant role in organ dysfunction.â¢ROS mediate the activation of MAPK pathways, potentially affecting distant organ.
IntroductionWe examined the activity of mitogen-activated protein kinase (MAPK) family members, extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38, in rats pinal cord after hind limb ischemia reperfusion (IR) and analyzed the role of reactive oxygen species (ROS) as mediators of MAPK signaling under these conditions.MethodsIn experiment 1, hind limb IR rats were treated intraperitoneally with one of following agents at 30Â min before reperfusion: allopurinol (4, 40Â mg/kg), superoxide dismutase (SOD, 4000Â U/kg), N-nitro-l-arginine methyl ester (l-NAME, 10Â mg/kg), or SOD (4000Â U/kg)Â +Â l-NAME (10Â mg/kg). In experiment 2, 5,10,15,20-tetrakis (N-methyl-4â²-pyridyl) porphyrinato iron (III) (FeTMPyP) was administered intraperitoneally (1, 3, or 10Â mg/kg) 30Â min before reperfusion. After 3Â d reperfusion period, the spinal cord (L4-6) was harvested to investigate MAPK signaling activity.ResultsIn experiment 1, p-ERK and p-JNK levels were significantly higher in the IR group than sham group. Administration of allopurinol, SOD, l-NAME, or SODÂ +Â l-NAME significantly reduced the IR-induced increase in p-ERK and p-JNK levels. There were no significant differences in p-p38 levels. In experiment 2, FeTMPyP significantly reduced the IR-induced increase in p-ERK and p-JNK levels in a dose-dependent manner.ConclusionsActivation of ERK and JNK in the spinal cord was induced by hind limb IR and was not accompanied by p38 activation. IR-induced MAPK phosphorylation was reduced by inhibition of superoxide, nitric oxide, and peroxynitrite, indicating that ROS produced by hind limb IR mediate the activation of these signaling pathways in the spinal cord, potentially affecting distant organs.