Aims: 

We evaluate whether the constitutive mitochondrial nitric oxide synthase (c-mtNOS) is related to the mitochondrial dysfunction in inflammation. We also assessed the effect of melatonin in this experimental paradigm.

Methods: 

The activities of cytosolic and mitochondrial nitric oxide synthases and mitochondrial bioenergetics were measured in heart of wild type and nNOS-deficient mice. Three experimental groups were done: control group, group of septic mice induced by cecal ligation and puncture (CLP) and group of septic mice treated with melatonin. Mice were killed 24 hours after sepsis induction and pure heart cytosol and mitochondrial fractions were prepared. Melatonin was administrated in four doses (30 mg/ kg b.w) as follows: 30 minutes before surgery, and 30 minutes, 4 hours and 8 hours after surgery.

Results: 

In both mice strains, CLP induced a similar increased activity of both iNOS/i-mtNOS, and a significant inhibition of the respiratory chain activity. Melatonin treatment counteracted these parameters in both mice strains, recovering the normal mitochondrial function.

Conclusions: 

These data suggest that c-mtNOS is not involved in the bioenergetic dysfunction during sepsis. Melatonin administration restores the functional mitochondrial activity that is depressed in this pathology.

Supported by grants: RD06/0013/0008 and P07-CTS-03135