Journal of Clinical and Translational Hepatology

Journal of Clinical and Translational Hepatology

Thursday, 10 / 18 / 2018

Articles

Glycosphingolipids Prevent APAP and HMG-CoA Reductase Inhibitors-mediated Liver Damage: A Novel Method for “Safer Drug” Formulation that Prevents Drug-induced Liver Injury

ORIGINAL ARTICLE

Glycosphingolipids Prevent APAP and HMG-CoA Reductase Inhibitors-mediated Liver Damage: A Novel Method for “Safer Drug” Formulation that Prevents Drug-induced Liver Injury

Meir Mizrahi, Tomer Adar, Gadi Lalazar, Dean Nachman, Madi El Haj, Ami Ben Ya’acov, Yoav Lichtenstein, Yehudit Shabat, Dimitri Kanovich, Lida Zolotarov and Yaron Ilan*

Gastroenterology and Liver Units, Department of Medicine, Hebrew University-Hadassah Medical Center, Jerusalem, Israel

*Correspondence to: Yaron Ilan, Department of Medicine, Hebrew University-Hadassah Medical Center, P.O.B 12000, Jerusalem, IL-91120, Israel. Tel: +972-2-6777816, Fax: +972-2-6431021, E-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.

Journal of Clinical and Translational Hepatology 2018;6(2):127-134 DOI: 10.14218/JCTH.2017.00071
Received: November 4, 2017 Accepted: January 23, 2018 Published online: February 14, 2018

Abstract

Background and Aims: Acetaminophen (APAP) and HMG-CoA reductase inhibitors are common causes of drug-induced liver injury (DILI). This study aimed to determine the ability to reduce APAP- and statins-mediated liver injury by using formulations that combine glycosphingolipids and vitamin E.

Methods: Mice were injected with APAP or with statins and treated before and after with β-glucosylceramide (GC), with or without vitamin E. Mice were followed for changes in liver enzymes, liver histology, hepatic expression of JNK, STAT3 and caspase 3, as well as intrahepatic natural killer T cells (NKT) and the serum cytokine levels by flow cytometry.

Results: Administration of GC before or after APAP alleviated the liver damage, as noted by a reduction of the liver enzymes, improvement in the liver histology and decreased hepatic caspase 3 expression. Beneficial effect was associated with a reduction of the intrahepatic NKT, JNK expression in the liver, and increased glutathione in the liver, and decreased TNF-α serum levels. Synergistic effect of co-administration of GC with vitamin E was observed. Similar protective effect of GC on statin-mediated liver damage was documented by a reduction in liver enzymes and improved liver histology, which was mediated by reduction of NKT, increased STAT3 expression in the liver, and reduced the TGF-β and IL17 levels.

Conclusions: β-glycosphingolipids exert a hepatoprotective effect on APAP- and statins-mediated liver damage. Vitamin E exerted a synergistic effect to that of GC. The generation of “safer drug” formulations, which include an active molecule combined with a hepatoprotective adjuvant, may provide an answer to the real unmet need of DILI.

Keywords

Acetaminophen, Statins, Glycosphingolipids

 

 

Journal of Clinical and Translational Hepatology 2018 vol. 6, 127-134  [ Html ] [ PDF Full-text ]

© The Authors 2018. This article is published under the terms of the Creative Commons Attribution-Noncommercial License (CC BY-NC 4.0), which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license.

 

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