Nox2 over-activation in children with non-alcoholic fatty liver disease.
Background: NADPH oxidase-2 (Nox2)-derived oxidative stress is believed to play a pivotal role in inducing non-alcoholic fatty liver disease (NAFLD) but its behavior in children with NAFLD has never been investigated.
Aim: To assess Nox2 activation in children affected by biopsy proven NAFLD. Furthermore, the association, of Nox2 activation with gut permeability and histological characteristics, will be analyzed in this population.
Methods: In a cross-sectional study we want to evaluate NOX2 activation (as assessed by sNOX2-dp serum levels), oxidative stress (as assessed by serum isoprostanes), gut permeability (assessed by plasma zonulin) and LPS levels in patients with NAFLD (n=65) and controls (n=65). Then, we will analyze the same parameters in NAFLD children with or without non-alcoholic steatohepatitis (NASH) and the activation of Nox2 with histological characteristics (steatosis, inflammation, ballooning, fibrosis, NAFLD Activity Score (NAS)).
Expected results: preliminary data from a pilot study showed that compared to controls, NAFLD patients had higher Nox2 activity, isoprostanes, zonulin and LPS levels. These data must be confirmed by this proposed research study. Furthermore, multivariate linear regression analysis will be performed to assess the variables independently associated with sNox2-dp levels. We expect to have, within NAFLD group, significant higher levels of sNox2-dp, isoprostanes, LPS patients in patients with NASH compared to those without NASH.
This study could provides evidences in children with NAFLD about the role of Nox2 activation and the degree of liver damage. Furthermore, the study will analyse the relationship between Nox2 and LPS serum,, that could play a potential role for gut-derived LPS in eliciting systemic Nox2 activation.