Serum Oxidative Stress Markers and Lipidomic Profile to Detect NASH Patients Responsive to an Antioxidant Treatment: A Pilot Study

Stiuso, Paola; Scognamiglio, Ilaria; Murolo, Marianna; Ferranti, Pasquale; Simone, Carmela De; Rizzo, Maria Rosaria; Tuccillo, Concetta; Caraglia, Michele; Loguercio, C.; Federico, Alessandro

doi:10.1155/2014/169216

Cited by 70 publications

(74 citation statements)

References 27 publications

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“…For example, MALDI-IMS has been used to visualize the heterogeneous distribution of PC species in mouse brains [34], and effects of traumatic brain injury on the differential localization of PCs in rat brains [35]. Furthermore, MALDI-IMS detected alterations in phospholipid zonation in human livers with steatosis or nonalcoholic steatohepatitis (NASH) [36], and MALDI-TOF was used to measure serum lipidomic profiles in patients with NASH [37]. The present study examines the utility of MALDI-IMS for distinguishing glycerophospholipid profiles in experimental steatohepatitis produced in Long Evans rats by chronic ethanol, NNK or ethanol+NNK exposures.…”

Section: Introductionmentioning

confidence: 99%

Differential Lipid Profiles in Experimental Steatohepatitis: Role for Imaging Mass Spectrometry as a Diagnostic Aid

Yalçın¹,

Nunez²,

Cornett³

2015

J Drug Alcohol Res

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Background. Ethanol, tobacco-specific nitrosamine ketone (NNK), and ethanol+NNK exposures cause steatohepatitis, suggesting that smoking can be a cofactor in alcoholic liver disease. Study design. We used MALDI-TOF imaging mass spectrometry (IMS) to characterize hepatic lipid profiles in steatohepatitis caused by ethanol, NNK, and ethanol+NNK. Results. Ethanol, NNK, and ethanol+NNK increased levels and altered the profiles of hepatic phospholipids. Ethanol caused striking accumulations of m/z 932.7 phosphatidylinositol (PI). NNK increased hepatic levels of PIs with m/z's of 934.8, 960.8, and 962.7. Relative abundance of PIs with m/z's of 857.9 or 883.7 increased progressively from control to NNK, then ethanol, and finally ethanol+NNK, indicating differential and additive effects of these exposures. In contrast, no differences occurred with respect to phosphatidylethanolamine (m/z 766.9), phosphatidylserine (m/z 810.9) or PIs with m/z of 960.8 or 962.7. Principal component analysis generated distinct exposure-related hepatic lipid profiles. Conclusion. MALDI-IMS could serve as a complementary diagnostic aid for differentiating underlying causes of steatohepatitis.

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Section: Introductionmentioning

confidence: 99%

Differential Lipid Profiles in Experimental Steatohepatitis: Role for Imaging Mass Spectrometry as a Diagnostic Aid

Yalçın¹,

Nunez²,

Cornett³

2015

J Drug Alcohol Res

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“…The therapeutic response, mainly demonstrated by the improvement of liver damage, is reached in approximately 50% of the treated subjects. Moreover, we recently reported that this response was significantly correlated with the baseline serum oxidative stress, as well as with the variations of the serum oxidative and lipidomic profiles (16). In particular, we demonstrated that sera from patients with NASH induced lipid droplet accumulation in the cytoplasm of HepG2 cells, whereas a conditioning of the cells with sera of patients treated with silybin led to a reduction of intracellular fat accumulation.…”

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confidence: 64%

“…As reported in a previous study (16), we identified patients showing very low or very high levels of TBARS at baseline when compared to those of healthy controls. Thus, we divided patients (both P and R) into two groups on the basis of the trend of TBARS serum levels between baseline and after 12 months of treatment with P or R, in order to evaluate any potential differences of antioxidant response between these two groups.…”

Section: Resultsmentioning

confidence: 97%

“…As in a previous study (16), we identified an opposite trend in TBARS levels among the patients treated with R. Thus, we divided the patients into two groups on the basis of the incremental or decremental trend of TBARS levels, P/R-I and P/R-II, respectively. On the basis of this subdivision, we found, at the end of 12 months of R administration, a decrease of CAT activity in patients showing an increase of TBARS, whereas no change in patients showing a decrease of TBARS was found (R-I group).…”

Section: Figure 2 Serum Levels Of Thiobarbituric Acid Reactive Substmentioning

confidence: 82%

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A Long-term Treatment with Silybin in Patients with Non-alcoholic Steatohepatitis Stimulates Catalase Activity in Human Endothelial Cells

Federico

Conti

Russomanno

et al. 2017

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Abstract. Aim: To compare levels of oxidative stress markers in patients' sera with non-alcoholic steatohepatitis (NASH) treated for 12 months (T 12 ) with silybin conjugated with phosphatidylcholine (Realsil ® ) (R) or placebo (P) and investigate oxidative stress responses in human endothelial 001). By dividing patients into two groups, increased (P-I/R-I) and decreased TBARS (P-II/R-II) at T 12 compared to T 0 , we found an increased CAT activity in conditioned endothelial cells at T12 in both groups (p=0.05 and p=0.001, respectively). Conclusion: Realsil ® may be effective against endothelial dysfunction by stimulating the cellular antioxidant defense.Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide (1). NAFLD is characterized by fat accumulation in the liver, leading to clinical conditions ranging from isolated steatosis to chronic inflammatory status represented by fibrosis, cirrhosis and hepatocellular carcinoma (2). In NAFLD patients, the amount of liver enzymes has been demonstrated to predict the incidence of cardiovascular diseases (CVDs), independently from the traditional risk factors, including C-reactive protein and metabolic syndrome (MS). Moreover, the extent of liver damage has been correlated with early carotid atherosclerosis, suggesting that the injury to both vessels and liver share inflammatory mediators (3). For these reasons, NAFLD has been recently proposed as an early marker of atherosclerosis and endothelial dysfunction and, consequently, as an independent cardiovascular risk factor (4).In insulin-resistant subjects, the presence of fatty liver has been correlated with an impairment of the systemic oxidant/antioxidant balance (indicated as oxidative stress) and endothelial dysfunction, independently from the presence of MS, adiposity and high levels of adipokines (4). It is well-known that oxidative stress is associated with endothelial dysfunction and CVD (5, 6) and, in NAFLD patients, it triggers an inflammatory cascade and extracellular matrix deposition in the liver, favoring the development of non-alcoholic steatohepatitis (NASH). Even if the mechanisms linking NALFD to increased oxidative stress and endothelial dysfunction have not yet been fully clarified, impaired mitochondrial β-oxidation, high levels of oxidized low-density lipoprotein (LDL), dietary saturated fat and reduced antioxidant intake have been proposed as potential pathogenetic factors (7-10).Administration of several natural polyphenols is now considered to be a valid therapeutic strategy due to the ability of these compounds in preserving endothelial function and contrasting CVD (11). Silybin, the major active constituent of silymarin, is a potent antioxidant agent (12). It attenuates the 609 This article is freely accessible online.

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“…The harmful effect of free radicals, intracellularly, is counteracted by the ability of cells to maintain the oxidative stress balance; oxidative stress occurs when the balance "prooxidant/antioxidant" is disturbed, and it generates the alteration of cellular structures, thus affecting lipid components, proteins, and nucleic acids [7].…”

Section: Introductionmentioning

confidence: 99%

Serum Levels of Oxidative Stress Markers in Patients with Type 2 Diabetes Mellitus and Non-alcoholic Steatohepatitis

Casoinic

Sampelean

Buzoianu

et al. 2016

Romanian Journal of Internal Medicine

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Introduction. Oxidative stress is one of the key mechanisms responsible for disease progression in non-alcoholic fatty liver disease. The aim of this study was to evaluate the serum levels of oxidative stress markers in patients with type 2 diabetes mellitus (DMT2) and non-alcoholic steatohepatitis (NASH) and test their relationships with clinical and biochemical patient characteristics, compared to patients with DMT2 without non-alcoholic fatty liver disease (NAFLD), and controls.Materials and methods. In all, 60 consecutive patients with DMT2 and NASH, 55 with DMT2 without NAFLD, and 50 age-and-gender-matched healthy subjects participated in the study. The serum levels of protein carbonyls and 8-isoprostane were determined by ELISA methods, while the serum levels of malondialdehyde (MDA) were detected by means of the spectrophotometric method. Clinical, demographic, and laboratory parameters were examined for all the subjects included in the study. Multivariate logistic regression was used to test the independent predictive factors in the relationships investigated here.Results. Patients with DMT2 and NASH displayed significantly higher serum levels of protein carbonyls (1.112 ± 0.42 nmol/dL), MDA (6.181 ± 1.81 ng/mL), and 8-isoprostane (338.6 ± 98.5 pg/mL) compared to patients with DMT2 without NAFLD, and controls. Results of multivariate logistic regression analyses indicate that in patients with DMT2 and NASH, the serum levels of oxidative stress markers were independently and positively associated with: HbA1c, duration of diabetes, the UKPDS cardiovascular risk score (for protein carbonyls); age, LDL-cholesterol (for 8-isoprostane); and triglycerides serum levels (for MDA).Conclusions. Our findings indicate that the process of oxidative stress tends to increase in patients with DMT2 and NASH, compared to patients with DMT2 without NAFLD, and controls. This evidence suggests that an antioxidant therapy might prove useful in the treatment of patients with DMT2 and NASH.

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Serum Oxidative Stress Markers and Lipidomic Profile to Detect NASH Patients Responsive to an Antioxidant Treatment: A Pilot Study

Cited by 70 publications

References 27 publications

Differential Lipid Profiles in Experimental Steatohepatitis: Role for Imaging Mass Spectrometry as a Diagnostic Aid

Differential Lipid Profiles in Experimental Steatohepatitis: Role for Imaging Mass Spectrometry as a Diagnostic Aid

A Long-term Treatment with Silybin in Patients with Non-alcoholic Steatohepatitis Stimulates Catalase Activity in Human Endothelial Cells

Serum Levels of Oxidative Stress Markers in Patients with Type 2 Diabetes Mellitus and Non-alcoholic Steatohepatitis

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