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Int. J. Mol. Sci. 2014, 15(11), 21202-21214; doi:10.3390/ijms151121202

Plasma Levels of Homocysteine and Cysteine Increased in Pediatric NAFLD and Strongly Correlated with Severity of Liver Damage

1
Metabolomics and Proteomics Unit, "Bambino Gesù" Children's Hospital, IRCCS, Rome 00165, Italy
2
Liver Research Unit, "Bambino Gesù" Children's Hospital, IRCCS, Rome 00165, Italy
3
Hepato-Metabolic Disease Unit, "Bambino Gesù" Children's Hospital, IRCCS, Rome 00165, Italy
These authors equally contributed to this work.
*
Authors to whom correspondence should be addressed.
Received: 17 October 2014 / Revised: 10 November 2014 / Accepted: 10 November 2014 / Published: 17 November 2014
(This article belongs to the Collection Molecular Mechanisms of Human Liver Diseases)
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Abstract

Non-alcoholic fatty liver disease (NAFLD) is a spectrum of metabolic abnormalities ranging from simple triglyceride accumulation in the hepatocytes to hepatic steatosis with inflammation, ballooning and fibrosis. It has been demonstrated that the pathogenesis of NAFLD involves increased oxidative stress, with consumption of the major cellular antioxidant, glutathione (GSH). Liver has a fundamental role in sulfur compound metabolism, although the data reported on plasma thiols status in NAFLD are conflicting. We recruited 63 NAFLD patients, and we analyzed all plasma thiols, such as homocysteine (Hcy), cysteine (Cys), cysteinylglycine (CysGly) and GSH, by high-performance liquid chromatography (HPLC) with fluorescence detection. Hcy, Cys and CysGly plasma levels increased in NAFLD patients (p < 0.0001); whereas GSH levels were decreased in NAFLD patients when compared to controls (p < 0.0001). On the contrary, patients with steatohepatitis exhibited lower levels of Hcy and Cys than subjects without. Furthermore, a positive correlation was found between Hcy and Cys and the presence of fibrosis in children with NAFLD. Taken together, these data demonstrated a defective hepatic sulfur metabolism in children with NAFLD, and that high levels of Hcy and Cys probably correlates with a pattern of more severe histological liver damage, due to mechanisms that require further studies. View Full-Text
Keywords: homocysteine; cysteine; cysteinylglycine; glutathione; non-alcoholic fatty liver disease (NAFLD); non-alcoholic steatohepatitis (NASH) homocysteine; cysteine; cysteinylglycine; glutathione; non-alcoholic fatty liver disease (NAFLD); non-alcoholic steatohepatitis (NASH)
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Pastore, A.; Alisi, A.; di Giovamberardino, G.; Crudele, A.; Ceccarelli, S.; Panera, N.; Dionisi-Vici, C.; Nobili, V. Plasma Levels of Homocysteine and Cysteine Increased in Pediatric NAFLD and Strongly Correlated with Severity of Liver Damage. Int. J. Mol. Sci. 2014, 15, 21202-21214.

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