Oxidative stress parameters in paediatric non-alcoholic fatty liver disease

Abstract

Abstract.We have investigated the presence and the possible clinical implications of oxidative stress in children with nonalcoholic fatty liver disease (NAFLD). The present study was an observational study of oxidative stress parameters in the progression of paediatric NAFLD. We observed the role of oxidative stress in children diagnosed with NAFLD by evaluating: serum protein carbonyls, hepatic expression of 8-hydroxy-2-deoxyguanosine (8-OHG), and circulating antibody against malondialdehyde adducted human serum albumin (MDA-HSA). Forty consecutive children with biopsy-proven NAFLD (27 male; 13 female) referred to Bambino Gesù Children's Hospital, Rome, Italy, from January 2007 to April 2008 were included in the study. Serum variations of protein carbonyls, 8-OHG, and circulating antibody against MDA-HSA were evaluated. Elevated protein carbonyls were evident in 33 subjects (83%) irrespective of obesity and insulin resistance. Moreover, liver biopsies of NAFLD patients positive for circulating protein carbonyls also showed a significant increase in the nuclear staining for 8-OHG (p=0.006; 95% CI 3.1-17.7). Anti-MDA-HSA IgG above control threshold was detected in 25 (63%) children. Although protein carbonyl levels were unrelated with disease severity, patients with elevated anti-MDA-HSA IgG had scores for lobular inflammation significantly higher (p=0.019) than subjects with antibodies within the control range, while steatosis, hepatocyte ballooning and fibrosis were similar. High anti-MDA-HSA reactivity was also associated with a 13-fold increased risk (OR=12.9; 95% CI 1.5-113.8; p=0.013) of a NAFLD activity score (NAS) ≥5. These results demonstrate that oxidative stress has an high prevalence in children with NAFLD and is associated with an increased severity of steatohepatitis.

Role of oxidative stress and insulin resistance in disease severity of non-alcoholic fatty liver disease

“…Hepatic oxidative injury was associated with the development of antibodies toward protein-adducted MDA in a significant proportion of children with NAFLD (63%) and in ~40% of adult patients with NAFLD (25). In a previous study, plasma NO and plasma MDA levels were significantly higher, and plasma vitamin E and C levels were significantly lower in patients with NASH than in those with NAFL (29).…”

“…Depletion of GH, a major cellular antioxidant, has been reported in NAFLD (25). Leach et al (16) recently demonstrated that NASH was an independent predictor of decreased GH levels and patients with NASH had significantly lower levels of antioxidants.…”

The balance between IL-17 and IL-22 produced by liver-infiltrating T-helper cells critically controls NASH development in mice

“…CD4 + Th cells assist B-cells and CD8 + cytotoxic cells in the activation and perpetuation of immune and autoimmune reactions [12]. Consistently, IgG against antigens originating from oxidative stress products are detectable in NAFLD/NASH patients [13,14] and immunization of mice with lipid peroxidation products exacerbated NASH development [10]. Inflammation is a main pathological feature of NASH, and cells of adaptive immunity, along with cells of innate immunity, can trigger and sustain hepatic inflammatory reactions [12].…”

Urinary 1H-NMR-based metabolic profiling of children with NAFLD undergoing VSL#3 treatment

“…27 The urinary psi levels mainly originate from ribosomal and transfer RNA degradation, reflecting RNA turnover 28 and hence protein turnover, as recently reported. [29][30][31] Actually, these metabolic incomes could be increased by oxidative modifications occurring in pediatric NAFLD, [32][33] including high dietary energy intake. 33 It is now well recognized that, in humans, NAFLD is associated with increased IP and small intestinal bacterial overgrowth, and these factors are associated with the severity of the liver tissue damage.…”