Article

Hepatoprotectant Ursodeoxycholyl Lysophosphatidylethanolamide Increasing Phosphatidylcholine Levels as a Potential Therapy of Acute Liver Injury

Department of Internal Medicine IV, University Heidelberg Hospital Heidelberg, Germany.
Frontiers in Physiology (Impact Factor: 3.53). 02/2012; 3:24. DOI: 10.3389/fphys.2012.00024
Source: PubMed

ABSTRACT

It has been long known that hepatic synthesis of phosphatidylcholine (PC) is depressed during acute such as carbon tetrachloride-induced liver injury. Anti-hepatotoxic properties of PC as liposomes have been recognized for treatment of acute liver damage. Ursodeoxycholate (UDCA) is a known hepatoprotectant in stabilizing cellular membrane. For therapeutic management of liver injury, we coupled UDCA with a phospholipid known as ursodeoxycholyl lysophosphatidylethanolamide (UDCA-LPE). UDCA-LPE has been shown to first-in-class hepatoprotectant being superior to UDCA or PC. It inhibits mitochondrial damage and apoptosis, elicits survival signaling pathway, and promotes regeneration of hepatocytes. We herein report that a unique contribution of UDCA-LPE in increasing concentrations of PC in vitro and in vivo. UDCA-LPE-treated hepatocytes contained significantly increased PC levels. UDCA-LPE underwent the hydrolysis to LPE which was not the precursor of the increased PC. The levels of PC in the liver and blood were increased rapidly after intraperitoneally administration UDCA-LPE, and were found to be sustained even after 24 h. Among PC synthesis genes tested, UDCA-LPE treatment of mouse hepatocytes increased transcription of CDP-diacylglycerol synthase 1 which is an enzyme catalyzing phosphatidic acid to generate intermediates for PC synthesis. Thus, UDCA-LPE as a hepatoprotectant was able to induce synthesis of protective PC which would supplement for the loss of PC occurring during acute liver injury. This property has placed UDCA-LPE as a candidate agent for therapy of acute hepatotoxicity such as acetaminophen poisoning.

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    • "MSC exhibits additional anti-inflammatory properties, thus, may lead to an attenuated inflammatory response. Chamulitrat et al. (2012) suggest a derivative of ursodeoxycholic acid as possible novel treatment option. For the majority of individuals with fulminant ALF, however , a liver transplant (LTx) remains the only curative option. "

    Full-text · Article · Jan 2014 · Frontiers in Physiology
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    • "Cell lysates were subjected to lipid extraction in the presence of D 4 -UDCA as an internal standard. UDCA-LPE and UDCA concentrations in samples and standards were determined using a liquid chromatography mass spectrometer (Waters 2695 interfaced with a Quattro Micro; Waters, Milford, MA) (Chamulitrat et al., 2012). Fig. 1 "
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