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Acta Physiologica 2012; Volume 206, Supplement 693
Joint FEPS and Spanish Physiological Society Scientific Congress 2012
9/8/2012-9/11/2012
Santiago de Compostela, Spain
MODULATION OF THE NF-KAPPAB PATHWAY BY MELATONIN IN SEPTIC AGED MICE
Abstract number: P176
Volt Valdivia1 H, Garcia Santos1 J.A, Doerrier1 C, Venegas1 C, Lopez1 L.C, Bullejos1 J, Escames1 G, Acuna-Castroviejo1 D
1Physiology, University of Granada
Objectives:
NF-kB is a transcription factor which plays a critical role in the coordination of the immune innate response in sepsis, through the regulation of multiple genes. It is known that age is accompanied by an exacerbation of the systemic inflammatory response and increased mortality in sepsis. Thus, we determined the NF-kB-dependent molecular pathways during sepsis in aged mice, as well as whether the antioxidant and anti-inflammatory properties of melatonin were able to counteract the septic process.
Materials:
Eighteen months-old C57BL/6 mice were grouped as follows: a) control group; b) septic group, and c) septic group plus melatonin. Sepsis was induced by cecal ligation and puncture. Melatonin was administered at doses of 30 mg/kg. Animals were sacrificed 8 hrs after induction of sepsis, and the hearts were removed and processed for mitochondrial respiration and analytical purposes. Molecules involves in the NF-kB responses to sepsis were measured by qRT-PCR and western-blot.
Results:
An increase in NF-kB activation was observed in septic mice, accompanied by an induction of proinflammatory cytokines, as well as iNOS. Sepsis induced an important mitochondrial failure assessed by respirometry. Melatonin modulated the nuclear translocation of NF-kB, with the consequent reduction in the levels of iNOS and proinflammatory cytokines, restoring the redox balance in septic mice and improving the mitochondrial bioenergetics.
Conclusions:
The results further support the anti-inflammatory effects of melatonin, showing its high therapeutic value. Due to the age-dependent reduction in the endogenous melatonin production, the relation between melatonin reduction and increased inflammatory response with age is discussed.
To cite this abstract, please use the following information:
Acta Physiologica 2012; Volume 206, Supplement 693 :P176