Oxidative stress has been shown to play a major role in the complex pathophysiological processes leading to organ failure during
sepsis. The aim of the present research was to evaluate the effect of different
melatonin nanoparticle (NP) carriers in an experimental animal model of
sepsis.
Poly-D,L-lactide-co-glycolide (PLGA [NP-A]) and
polyethylene glycol-co-(
poly-D,L-lactide-co-glycolide) (PLGA-PEG [NP-B]) were used to obtain
melatonin-loaded nanocarriers (10 mg/kg). Oxidative stress was measured in tissue homogenates by measuring
heme oxygenase-1 (HO-1) expression, total
thiol groups and
lipid hydroperoxides (LOOH). In vitro NPs showed a long lag time followed by a controlled release of
melatonin. All the different
melatonin formulations restored total
thiol group levels to those of controls in all the examined organs, with no significant changes among them. Both
melatonin NP formulations significantly decreased LOOH levels when compared with
sepsis vehicle animals. The stealth formulation NP-B was able to produce a more significant reduction in LOOH levels in the heart, lung and liver when compared with NP-A. No significant changes were observed between the two NP formulations in the kidney. Interestingly, HO-1 expression was differently affected following treatment with various
melatonin formulations. The NP-B formulation was more effective in inducing HO-1
protein compared with free
melatonin and NP-A, with the exception of the kidney. Taken together, our results show that
melatonin possesses a significant
antioxidant activity during
sepsis and that it is possible to improve this ability by delivering the compound with specific drug delivery systems.