Aim: 

During inflammation, the activity of the mitochondrial iNOS (i-mtNOS) increases, yielding high levels of NO^• responsible for oxidative/nitrosative damage and mitochondrial impairment. Here, we attempt to clarify the role of c-mtNOS in the mitochondrial failure during sepsis that is yet unknown.

Methods: 

Sepsis was induced by cecal ligation and puncture in wild-type mice (nNOS^+/+) and nNOS-deficient (nNOS^-/-) mice. Mitochondria were prepared from the hearts of these mice and analyzed for mitochondrial i-mtNOS and c-mtNOS activities, nitrites, lipid peroxidation (LPO), glutathione (GSH), and glutathione peroxidase (GPx) and reductase (GRd) activities. We also evaluated whether the administration of the antioxidant and anti-inflammatory melatonin, counteracted the sepsis-induced mitochondrial oxidative stress.

Results: 

Sepsis induced a significant and similar increase in mitochondrial oxidative stress in both nNOS^+/+ and nNOS^-/- mice. The differences between these two mice strains were no significant and correlated well with the impairment of these organella. Melatonin administration to nNOS^+/+ andnNOS^-/- mice restored the normal redox status and the mitochondrial homeostasis.

Conclusion: 

Our results suggest that c-mtNOS, the mitochondrial NOS isoform derived from cytosolic nNOS, is not involved in the mitochondrial dysfunction during sepsis, whereas melatonin treatment maintains the mitochondrial homeostasis in these conditions.

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