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Serum oxidative stress markers and lipidomic profile to detect NASH patients responsive to an antioxidant treatment: a pilot study.

ABSTRACT: Liver steatosis can evolve to steatohepatitis (NASH) through a series of biochemical steps related to oxidative stress in hepatocytes. Antioxidants, such as silybin, have been proposed as a treatment of patients with nonalcoholic fatty liver disease (NAFLD) and NASH. In this study, we evaluated, in patients with histologically documented NASH, the oxidant/antioxidant status and lipid "fingerprint" in the serum of NASH patients, both in basal conditions and after 12 months of treatment with silybin-based food integrator Realsil (RA). The oxidant/antioxidant status analysis showed the presence of a group of patients with higher basal severity of disease (NAS scores 4.67?±?2.5) and a second group corresponding to borderline NASH (NAS scores?=?3.8?±?1.5). The chronic treatment with RA changed the NAS score in both groups that reached the statistical significance only in group 2, in which there was also a significant decrease of serum lipid peroxidation. The lipidomic profile showed a lipid composition similar to that of healthy subjects with a restoration of the values of free cholesterol, lysoPC, SM, and PC only in group 2 of patients after treatment with RA. Conclusion. These data suggest that lipidomic and/or oxidative status of serum from patients with NASH could be useful as prognostic markers of response to an antioxidant treatment.

SUBMITTER: Stiuso P

PROVIDER: S-EPMC4060161 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Serum oxidative stress markers and lipidomic profile to detect NASH patients responsive to an antioxidant treatment: a pilot study.

Stiuso Paola P Scognamiglio Ilaria I Murolo Marianna M Ferranti Pasquale P De Simone Carmela C Rizzo Maria Rosaria MR Tuccillo Concetta C Caraglia Michele M Loguercio Carmelina C Federico Alessandro A

Oxidative medicine and cellular longevity 20140602

Liver steatosis can evolve to steatohepatitis (NASH) through a series of biochemical steps related to oxidative stress in hepatocytes. Antioxidants, such as silybin, have been proposed as a treatment of patients with nonalcoholic fatty liver disease (NAFLD) and NASH. In this study, we evaluated, in patients with histologically documented NASH, the oxidant/antioxidant status and lipid "fingerprint" in the serum of NASH patients, both in basal conditions and after 12 months of treatment with silyb ...[more]

PMID: 24987492

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Project description:In non-alcoholic steatohepatitis (NASH), many lines of investigation have reported a dysregulation in lipid homeostasis, leading to intrahepatic lipid accumulation. Recently, the role of dysfunctional sphingolipid metabolism has also been proposed. Human and animal models of NASH have been associated with elevated levels of long chain ceramides and pro-apoptotic sphingolipid metabolites, implicated in regulating fatty acid oxidation and inflammation. Importantly, inhibition of de novo ceramide biosynthesis or knock-down of ceramide synthases reverse some of the pathology of NASH. In contrast, cell permeable, short chain ceramides have shown anti-inflammatory actions in multiple models of inflammatory disease. Here, we investigated non-apoptotic doses of a liposome containing short chain C6-Ceramide (Lip-C6) administered to human hepatic stellate cells (hHSC), a key effector of hepatic fibrogenesis, and an animal model characterized by inflammation and elevated liver fat content. On the basis of the results from unbiased liver transcriptomic studies from non-alcoholic fatty liver disease patients, we chose to focus on adenosine monophosphate activated kinase (AMPK) and nuclear factor-erythroid 2-related factor (Nrf2) signaling pathways, which showed an abnormal profile. Lip-C6 administration inhibited hHSC proliferation while improving anti-oxidant protection and energy homeostasis, as indicated by upregulation of Nrf2, activation of AMPK and an increase in ATP. To confirm these in vitro data, we investigated the effect of a single tail-vein injection of Lip-C6 in the methionine-choline deficient (MCD) diet mouse model. Lip-C6, but not control liposomes, upregulated phospho-AMPK, without inducing liver toxicity, apoptosis, or exacerbating inflammatory signaling pathways. Alluding to mechanism, mass spectrometry lipidomics showed that Lip-C6-treatment reversed the imbalance in hepatic phosphatidylcholines and diacylglycerides species induced by the MCD-fed diet. These results reveal that short-term Lip-C6 administration reverses energy/metabolic depletion and increases protective anti-oxidant signaling pathways, possibly by restoring homeostatic lipid function in a model of liver inflammation with fat accumulation.

Project description:BackgroundIt has been suggested that premenstrual syndrome (PMS) may derive from either elevated oxidative stress or reduced antioxidant vitamin levels in the body; however, these relationships have been minimally studied in a large cohort of healthy women. Our objective was to estimate the association between serum concentrations of antioxidant vitamins (A, C, and E) and markers of oxidative stress (F2-isoprostane) with symptoms and severity of PMS.MethodsThe BioCycle study was a prospective cohort study following 259 healthy premenopausal women aged 18-44 years for up to 2 menstrual cycles. Frequency/severity of 20 PMS symptoms were assessed via questionnaires 4 times/cycle, and antioxidant vitamins and oxidative stress biomarkers were measured up to 8 times/cycle to correspond with specific cycle phases. Generalized linear models were used to estimate associations between mean antioxidant concentrations and oxidative stress biomarkers with PMS symptoms and severity; linear mixed models were used to evaluate associations with symptom severity scores within groups (e.g. depression, cravings, pain).ResultsHigher concentrations of serum antioxidant vitamins were largely not associated with prevalence or severity of PMS symptoms. Though a few associations were observed, only associations between mean γ-tocopherol and decreased odds of swelling of the hands/feet survived adjustment for multiple comparisons (OR 0.33, 95% CI 0.16, 0.65, per ug/dL). However, F2-isoprostanes were associated with prevalence and severity of several symptoms specifically related to depression and cravings (depression score β = 0.07, 95% CI 0.02, 0.12, per 10 ug/dL; cravings score β = 0.16, 95% CI 0.10, 0.22, per 10 ug/dL), as well as with classification of PMS severity (OR 1.07, 95% CI 1.01, 1.14, per 10 pg/dL), with these associations surviving adjustment for false discovery rate.ConclusionsF2-isoprostanes, but not antioxidant vitamins, were associated with select PMS symptoms, as well as symptom and severity categories. Specific symptom relationships merit further research.

Dataset Information

Serum oxidative stress markers and lipidomic profile to detect NASH patients responsive to an antioxidant treatment: a pilot study.

Publications

Serum oxidative stress markers and lipidomic profile to detect NASH patients responsive to an antioxidant treatment: a pilot study.

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