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Báo cáo khoa học: Attenuation of cardiac mitochondrial dysfunction by melatonin in septic mice

The existence of an inducible mitochondrial nitric oxide synthase has been recently related to the nitrosative⁄oxidative damage and mitochondrial dys-function that occurs during endotoxemia. Melatonin inhibits both inducible nitric oxide synthase and inducible mitochondrial nitric oxide synthase activities, a finding related to the antiseptic properties of the indoleamine. | ỊFEBS Journal Attenuation of cardiac mitochondrial dysfunction by melatonin in septic mice Germaine Escames1 Luis C. Lopez1 Francisco Ortiz1 Ana Lopez1 Jose A. García1 Eduardo Ros2 and Dario Acuna-Castroviejo1 3 1 Institute de Biotecnologia Departamento de Fisiologia Universidad de Granada Spain 2 Servicio de Angiologia y Cirugia Vascular HospitalUniversitario San Cecilio Granada Spain 3 Servicio de Analisis Clinicos HospitalUniversitario San Cecilio Granada Spain Keywords ATP production mitochondrialfailure mitochondrialnitric oxide synthase oxidative stress therapy Correspondence D. Acuna-Castroviejo Departamento de Fisiologia Facultad de Medicina Avenida de Madrid 11 E-18012 Spain Fax 34 958246295 Tel 34 958246631 E-mail dacuna@ugr.es Received 4 December 2006 revised 9 February 2007 accepted 23 February 2007 doi 10.1111 j.1742-4658.2007.05755.x The existence of an inducible mitochondrial nitric oxide synthase has been recently related to the nitrosative oxidative damage and mitochondrial dysfunction that occurs during endotoxemia. Melatonin inhibits both inducible nitric oxide synthase and inducible mitochondrial nitric oxide synthase activities a finding related to the antiseptic properties of the indoleamine. Hence we examined the changes in inducible nitric oxide synthase indu-cible mitochondrial nitric oxide synthase expression and activity bioenergetics and oxidative stress in heart mitochondria following cecal ligation and puncture-induced sepsis in wild-type iNOS and inducible nitric oxide synthase-deficient iNOS7 mice. We also evaluated whether melatonin reduces the expression of inducible nitric oxide synthase inducible mitochondrial nitric oxide synthase and whether this inhibition improves mitochondrial function in this experimental paradigm. The results show that cecal ligation and puncture induced an increase of inducible mitochondrial nitric oxide synthase in iNOS mice that was accompanied by oxidative stress respiratory chain impairment and .