Methylene blue protects liver oxidative capacity after gut ischaemia-reperfusion in the rat

O. Collange, A. L. Charles, J. Bouitbir, M. P. Chenard, J. Zoll, P. Diemunsch, F. Thaveau, N. Chakfé, F. Piquard, B. Geny

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Objectives: Mesenteric ischaemia/reperfusion (IR) may lead to liver mitochondrial dysfunction and multiple organ failure. We determined whether gut IR induces early impairment of liver mitochondrial oxidative activity and whether methylene blue (MB) might afford protection. Design: Controlled animal study. Materials and methods: Rats were randomised into three groups: controls (n = 18), gut IR group (mesenteric ischaemia (60 min)/reperfusion (60 min)) (n = 18) and gut IR + MB group (15 mg kg-1 MB intra-peritoneally) (n = 16). Study parameters were: serum liver function markers, blood lactate, standard histology and DNA fragmentation (apoptosis) on intestinal and liver tissue, maximal oxidative capacity of liver mitochondria (state 3) and activity of complexes II, III and IV of the respiratory chain measured using a Clark oxygen electrode. Results: Gut IR increased lactate deshydrogenase (+982%), aspartate and alanine aminotransferases (+43% and +74%, respectively) and lactate levels (+271%). It induced segmental loss of intestinal villi and cryptic apoptosis. It reduced liver state 3 respiration by 30% from 50.1 ± 3 to 35.2 ± 3.5 μM O2 min-1 g -1 (P < 0.01) and the activity of complexes II, III and IV of the mitochondrial respiratory chain. Early impairment of liver mitochondrial respiration was related to blood lactate levels (r2 = 0.45). MB restored liver mitochondrial function. Conclusions: MB protected against gut IR-induced liver mitochondria dysfunction.

Original languageEnglish (US)
Pages (from-to)168-175
Number of pages8
JournalEuropean Journal of Vascular and Endovascular Surgery
Volume45
Issue number2
DOIs
StatePublished - Feb 2013

Keywords

  • Acute mesenteric ischaemia
  • Ischaemia-reperfusion injury
  • Lactate
  • Liver mitochondria
  • Methylene blue

ASJC Scopus subject areas

  • Surgery
  • Cardiology and Cardiovascular Medicine

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