Severity of Hepatocyte Damage and Prognosis in Cirrhotic Patients Correlate with Hepatocyte Magnesium Depletion
Simona ParisseAlessandra GianoncelliGloria IsaniFrancesco Luigi GambaroGiulia AndreaniEmil MalucelliGiuliana AquilantiIlaria CarlomagnoRaffaella CarlettiMonica MischitelliF. FerriVeronica PaternaQuirino LaiGianluca MenniniFabio MelandroCira Di GioiaMassimo RossiStefano IottiMichela FratiniStefano Ginanni Corradini
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We aimed to evaluate the magnesium content in human cirrhotic liver and its correlation with serum AST levels, expression of hepatocellular injury, and MELDNa prognostic score. In liver biopsies obtained at liver transplantation we measured the magnesium content in liver tissue in 27 cirrhotic patients (CIRs) and 16 deceased donors with healthy liver (CTRLs) by atomic absorption spectrometry and within hepatocytes in 15 CIRs using synchrotron-based X-ray Fluorescence Microscopy. In 31 CIRs and 10 CTRLs we evaluated the immunohistochemical expression in hepatocytes of the transient receptor potential melastatin 7 (TRPM7), a magnesium influx chanzyme also involved in inflammation. CIRs showed a lower hepatic magnesium content [117.2 (IQR 110.5-132.9) vs 162.8 (IQR 155.9-169.8) μg/g; p<0.001] and a higher percentage of TRPM7 positive hepatocytes [53.0 (IQR 36.8-62.0) vs 20.7 (10.7-32.8) %; p<0.001) than CTRLs. In CIRs, MELDNa and serum AST at transplant correlated: a) inversely with the magnesium content both in liver tissue and hepatocytes; b) directly with the percentage of hepatocytes stained intensely for TRPM7. The latter also directly correlated with worsening of MELDNa at transplant compared to waitlisting. Magnesium depletion and overexpression of its influx chanzyme TRPM7 in hepatocytes are associated with severity of hepatocyte injury and prognosis in cirrhosis. These data represent the pathophysiological basis for a possible beneficial effect of magnesium supplementation in cirrhotic patients.Keywords:
Pathophysiology
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Two experiments were conducted with sheep to determine the relative biological availability of various inorganic magnesium compounds. In experiment I, 25 yearling wethers were fed a magnesium deficient diet to reduce feed intake and then the increase in voluntary feed intake was measured in response to 500 mg of supplemental magnesium daily in the form of feed grade magnesium oxide and reagent grade magnesium carbonate, magnesium oxide and magnesium sulfate. In a second experiment, 24 wether lambs were used in a balance study involving magnesite and reagent grade magnesium carbonate, magnesium oxide and magnesium sulfate. Voluntary feed intake in Experiment I, when expressed as a multiple of consumption prior to magnesium repletion was 2.19, 1.94, 1.65 and 1.26 for reagent grade magnesium carbonate, reagent grade magnesium oxide, feed grade magnesium oxide and reagent grade magnesium sulfate, respectively (P<.01). Magnesium sulfate caused an appreciable diuresis, and the lower feed intake obtained may not relate directly to the availability of its magnesium. Based on absorption and retention data obtained in Experiment II, magnesium as reagent grade magnesium carbonate, oxide and sulfate was well utilized. The magnesium in magnesite was essentially totally unavailable.
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