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J Surg Res. 2014 Jun 1;189(1):32-40. doi: 10.1016/j.jss.2013.12.025. Epub 2014 Jan 3.

L-α-glycerylphosphorylcholine reduces the microcirculatory dysfunction and nicotinamide adenine dinucleotide phosphate-oxidase type 4 induction after partial hepatic ischemia in rats.

Author information

1
Institute of Surgical Research, University of Szeged, Szeged, Hungary.
2
Institute of Laboratory Animal Science and Experimental Surgery, RWTH Aachen University, Aachen, Germany.
3
Institute of Surgical Research, University of Szeged, Szeged, Hungary. Electronic address: boros.mihaly@med.szote.u-szeged.hu.

Abstract

BACKGROUND:

We set out to investigate the microcirculatory consequences of hepatic ischemia-reperfusion (IR) injury and the effects of L-alpha-glycerylphosphorylcholine (GPC), a deacylated phospholipid derivative, on postischemic hepatocellular damage, with special emphasis on the expression of nicotinamide adenine dinucleotide phosphate oxidase type 4 (NOX4), which is predominantly expressed in hepatic microvessels.

MATERIALS AND METHODS:

Anesthetized male Sprague-Dawley rats were subjected to 60-min ischemia of the left liver lobes and 180-min reperfusion, with or without GPC treatment (50 mg/kg intravenously 5 min before reperfusion, n = 6 each). A third group (n = 6) served as saline-treated control. Noninvasive online examination of the hepatic microcirculation was performed hourly by means of modified spectrometry. Plasma tumor necrosis factor (TNF-α), high-mobility group box 1 protein (HMGB1), plasma aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase levels, tissue xanthine oxidoreductase (XOR) and myeloperoxidase (MPO) activities, and expressions of NOX2 and NOX4 proteins were determined.

RESULTS:

Liver IR resulted in significant increases in NOX2 and NOX4 expressions and XOR and MPO activities, and approximately 2-fold increases in the levels of the inflammatory cytokines TNF-α and HMGB1. The microvascular blood flow and tissue oxygen saturation decreased by ∼20% from control values. GPC administration ameliorated the postischemic microcirculatory deterioration and reduced the liver necroenzyme levels significantly; the NOX4 expression, MPO activity, and HMGB1 level were also decreased, whereas the NOX2 expression, TNF-α level, and XOR activity were not influenced by GPC pretreatment.

CONCLUSIONS:

NOX4 activation is a decisive component in the IR-induced microcirculatory dysfunction. Exogenous GPC ameliorates the inflammatory activation, and preserves the postischemic microvascular perfusion and liver functions, these effects being associated with a reduced hepatic expression of NOX4.

KEYWORDS:

HMGB1; Ischemia-reperfusion; Liver; Microcirculation; Modified spectrometry; Myeloperoxidase; NOX2; NOX4; TNF-α

PMID:
24636100
DOI:
10.1016/j.jss.2013.12.025
[Indexed for MEDLINE]

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